Høyt spill med pasienter (farmatid.no 22.11.2010)

Syge risikerer forkert medicin (dr.dk 19.10.2009)

Ansvar og oppfølging ved bruk av legemidler utenfor godkjent indikasjon (farmatid.no 22.11.2010)

Om forskrivning uten vitenskapelig støtte Psykiatriske legemidler og allergilegemidler var de mest sannsynlige typer legemidler som ble brukt utenfor preparatomtale med liten vitenskapelig støtte. I virkeligheten manglet vitenskapelig støtte for 96 % av de psykiatriske legemidler forskrevet utenfor preparatomtale. (Psychiatric drugs and allergy medications were the most likely types of drugs to be used off-label with little scientific support. In fact, scientific support was lacking for 96% of the psychiatric drugs prescribed off-label.) (latimes.com 15.5.2006)

Abbott Laboratories betaler 1,6 milliarder dollar for å promotere valproate (Depakote) utenfor preparatomtale (BMJ 2012;344:e3343 (11 May))

- Forskrivning utenfor preparatomtale høyest for psykofarmaka (Arch Intern Med. 2012 (Published online April 16))

Drug Maker Will Pay Fine for Promoting Off-Label Use (nytimes.com 30.8.2006)

Waxman undersøker industri-møte med FDA (businessweek.com 22.1.2008)

- Utstrakt forskrivning utenfor preparatomtale gir grunnlag for sikkerhetsbekymringer

Alarmerende resultater
Undersøgelse: Ulovlig markedsføring af lægemidler

bt.dk 27.6.2011
Den danske lægemiddelindustri bryder reglerne, når industriens sælgere opsøger læger for at markedsføre deres medicin.

Over halvdelen af de praktiserende læger har således oplevet, at lægemiddelindustriens repræsentanter uopfordret fortæller lægerne, at et lægemiddel kan bruges til andet, end det er godkendt til. Det viser en rundspørge, som Praktiserende Lægers Organisation (PLO) har foretaget i samråd med DRs nyhedsmagasin, 21 Søndag.

Formanden for PLO, Henrik Dibbern, kalder det alarmerende:

- Jeg synes, det er gravalvorligt, for denne praksis er klart i strid med reglerne. Det her stiller et ganske alvorligt spørgsmålstegn ved lægemiddelindustriens samlede troværdighed, siger Henrik Dibbern til DR Nyheder.

Patienters sikkerhed er på spil
Undersøgelsen er baseret på svar fra 402 læger - og viser tydeligt, at de regler, der skal styre medicinalindustriens markedsføring ikke overholdes.

Ifølge reglerne må et medicinalfirmas sælgere således ikke reklamere for, at et lægemiddel kan bruges til andre sygdomme, end det er godkendt til. Alligevel har 51 procent af de praktiserende læger i undersøgelsen oplevet, at sælgerne har gjort lige netop det.

PLO-formanden mener, at det i sidste instans er patienternes sikkerhed, der er på spil, når industriens markedsføring ikke følger reglerne.

- Industrien har en voldsom påvirkning af lægerne, og når de ikke engang følger reglerne i vores kontakt med dem, så bliver vi meget bekymrede for, om den påvirkning er til gavn for vores patienter, og jeg er bange for, at svaret er, at det er den ikke et langt stykke af vejen, siger Henrik Dibbern. (...)

- Språkspalten. Bruk av legemidler utenfor godkjent indikasjon. Når et legemiddel brukes på annen måte enn den det er offisielt godkjent for, kalles det på engelsk off label.

(Anm: Språkspalten. Bruk av legemidler utenfor godkjent indikasjon. Når et legemiddel brukes på annen måte enn den det er offisielt godkjent for, kalles det på engelsk off label. Vi mener bruk utenfor godkjent indikasjon eller bruk utenfor godkjent preparatomtale er gode betegnelser på norsk. Tidsskr Nor Legeforen 2016; 136:448 (17.3.201.1.2008).)

(Anm: FDA to hold long-awaited meeting to review off-label marketing. After years of anticipation, the US Food and Drug Administration will hold a public, two-day meeting in November to review the extent to which so-called off-label information about medicines may be disseminated to physicians. (statnews.com 31.8.2016).)

(Anm: Veronika Barrabés.Veronika Barrabés er Country Manager i Novartis Norge AS. Hun har lang erfaring fra ulike selskap og stillinger i legemiddelindustrien og er engasjert og aktiv deltager i ulike LMI-utvalg. Like bra, bare billigere? (dagensmedisin.no 7.8.2014).)

(Anm: Off-label drug marketing: Who will decide what’s “truthful” when the evidence can’t be trusted? (…) Off-label promotion is currently illegal and with good reason: restricting the marketing of unapproved medical products is one of the main reasons why we have an FDA in the first place.  The FDA has lost ground on the issue in court in the past few years, with corporations successfully framing the restrictions as a free speech violation. (medicinenet.com 24.11.2016).)

- Off-label-brug af psykofarmaka til børn og unge i Danmark. (- I Danmark omfatter den estimerede gennemsnitlige off-label-rate 30-40% af ordinationerne i kliniske børne- og ungdomspsykiatriske populationer. De laveste rater gælder midler mod ADHD (2-3%) og de højeste gælder antipsykotika (96%) og melatonin (100%).) (- Off-label-brug er legal – og nødvendig, når der ikke er andre behandlingsmuligheder. I givet fald sker ordinationen alene på lægens ansvar, ikke producentens (Figur 1B + C).)

(Anm: Off-label-brug af psykofarmaka til børn og unge i Danmark. Når et medicinsk produkt intentionelt anvendes til et medicinsk formål, som ikke er i overensstemmende med den autoriserede produktinformation, kaldes det off-label-brug (Figur 1A). En ordination kan være offlabel i forhold til alder, indikation, dosis, administra tionsform eller behandlingsvarighed. Off-label-brug er legal – og nødvendig, når der ikke er andre behandlingsmuligheder. I givet fald sker ordinationen alene på lægens ansvar, ikke producentens (Figur 1B + C). (…) Omfanget af forskning i lægemidler til børn og unge er begrænset. Off-labelbrug er derfor et alvorligt problem, som krænker børn og unges ret til effektiv og sikker medicinsk behandling og lægger ansvaret for behandlingen på de ordinerende læger. - I Danmark omfatter den estimerede gennemsnitlige off-label-rate 30-40% af ordinationerne i kliniske børne- og ungdomspsykiatriske populationer. De laveste rater gælder midler mod ADHD (2-3%) og de højeste gælder antipsykotika (96%) og melatonin (100%). Efter en periode med forbrugsstigning af alle psykofarmaka til børn og unge er forbruget af melatonin stadig stigende, mens forbruget af de øvrige psykofarmaka er stabiliseret eller faldende trods stigende patienttilgang i børne- og ungdomspsykiatrien. - Trods regulatoriske initiativer fra de europæiske og nationale myndigheder er den psykofarmakologiske behandling af børn og unge udfordret af manglende evidens for effekt og sikkerhed. Dette rammer godt en tredjedel af de patienter, der er i medikamentel behandling i børne- og ungdomspsykiatrien. (…) SUMMARY Anne Katrine Pagsberg & Per Hove Thomsen: Off-label prescription of psychopharmacological drugs for children and adolescents Ugeskr Læger 2017;179:V05170355 Despite regulatory initiatives, psychopharmacological treatment of adolescents is challenged by missing trial data on efficacy and safety. In Denmark, an estimated mean offlabel prescription rate of 30-40% in clinical child- and adolescent mental health services has been found in recent studies. The lowest rates were found for drugs treating ADHD (2-3%), and the highest for antipsychotics (96%) and melatonin (100%). The use of melatonin is growing, while the use of other psychopharmacological drugs appears to be stabilizing or decreasing, in spite of an increased number of adolescents treated in Danish mental health services. Ugeskr Læger 2017;179:V05170355.)

- Antipsykotikas (nevroleptikas) hemming av kompleks I i cortex i normale menneskehjerner er en parallell til den ekstrapyramidale giftigheten til antipsykotika (neuroleptika). (…) Våre data støtter hypotesen om at antipsykotika (nevroleptika)-induserte ekstrapyramidale bivirkninger kan skyldes hemming av mitokondriell respiratorisk kjede.

(Anm: Antipsykotikas (nevroleptikas) hemming av kompleks I i cortex i normale menneskehjerner er en parallell til den ekstrapyramidale giftigheten til antipsykotika (nevroleptika). (…) Våre data støtter hypotesen om at antipsykotika (neuroleptika)-induserte ekstrapyramidale bivirkninger kan skyldes hemming av mitokondriell respiratorisk kjede.(Inhibition of complex I by neuroleptics in normal human brain cortex parallels the extrapyramidal toxicity of neuroleptics. (…) Our data support the hypothesis that neuroleptic-induced extrapyramidal side effects may be due to inhibition of the mitochondrial respiratory chain.) Mol Cell Biochem. 1997 Sep;174(1-2):255-9.)

(Anm: SSRI-preparater og antipsykotika har uheldige effekter på mitokondrier (mintankesmie.no).)

(Anm: Bivirkninger (legemiddelinduserte organskader og sykdommer) (mintankesmie.no).

(Anm: Mitokondriell dysfunksjon (mitokondriedysfunksjon) indusert av sertraline (Zoloft), et antidepressiva (Mitochondrial dysfunction induced by sertraline, an antidepressant agent) Toxicol Sci. 2012 Jun;127(2):582-91. Epub 2012 Mar 2.)

(Anm: Kan Lupus øke risikoen for demens? Could lupus raise dementia risk? People living with lupus may be at significantly greater risk of developing dementia than those without the autoimmune disease, a new study suggests. (…) Study co-author Daniela Amital, of the Sackler Faculty of Medicine at Tel Aviv University in Israel, and colleagues recently reported their results in the International Journal of Geriatric Psychiatry. (medicalnewstoday.com 9.11.2017).)

- Ifølge studie dobles forskrivningen av beroligende legemidler blant eldre mennesker ved innflytting på omsorgsinstitusjoner.

(Anm: Ifølge studie dobles forskrivningen av beroligende legemidler blant eldre mennesker ved innflytting på omsorgsinstitusjoner. BMJ 2013;346:f1272 (26 February 2013).)

(Anm: Alzheimer's drug prescribed off-label could accelerate cognitive decline for some patients. Donepezil, a medication that is approved to treat people with Alzheimer's disease, should not be prescribed for people with mild cognitive impairment without a genetic test. UCLA School of Nursing researchers discovered that for people who carry a specific genetic variation -- the K-variant of butyrylcholinesterase, or BChE-K -- donezpezil could accelerate cognitive decline. (news-medical.net 27.2.2017).)

(Anm: Bruk av antipsykotika blandt fosterhjemsungdom med diagnostisert ADHD øker (Antipsychotic drug use among ADHD-diagnosed foster care youth is increasing) (...) Antipsykotika forskrives ofte utenfor indikasjon, slik som behandling av barn og unge med oppmerksomhetssvikt-hyperaktivitets-syndrom (ADHD). Resultatene fra en studie på bruk av "atypiske antipsykotika" blant ungdom med ADHD, sammenlignet aldersgrupper, valgbarhet innen Medicaid, og bruk innen fosteromsorg er presentert i det fagfellevurderte medisinske tidsskriftet Journal of Child and Adolescent Psychopharmacology, fra utgiverne Mary Ann Liebert, Inc. (medicalnewstoday.com 9.4.2014).)

(Anm: Editorials. Off-label prescribing of antidepressants. Strength of evidence matters more than presence or absence of a specific licence. (…) In their paper (doi:10.1136/bmj.j603), Wong and colleagues found that almost a third of antidepressants were prescribed for off-label indications, most commonly pain, insomnia, and migraine.2 (…) Patients and prescribers should be cautious about all extrapolations of evidence whether the proposed treatment is “on-label” or “off-label.” BMJ 2017;356:j849 (Published 21 February 2017).)

(Anm: Off-label indications for antidepressants in primary care: descriptive study of prescriptions from an indication based electronic prescribing system. (…) Conclusions When primary care physicians prescribed antidepressants for off-label indications, these indications were usually not supported by strong scientific evidence, yet often another antidepressant in the same class existed that had strong evidence for the respective indication. There is an important need to generate and provide physicians with evidence on off-label antidepressant use to optimise prescribing decisions. BMJ 2017;356:j603 (Published 21 February 2017).)

(Anm: Legemiddelkonsulenter (sales representatives) (mintankesmie.no).)

(Anm: FDA invites pharma input in off-label debate. (…) Regulators are soliciting input on how to regulate communications about off-label uses for already approved medical products and devices. (biopharmadive.com 10.11.2016).)

- Off label en fråga också för EU-kommissionen. (- Off label-förskrivning är ett hett ämne, såväl inom EU som i Sverige. En rapport i ämnet som EU-kommissionen arbetar med är två år försenad, men förväntas bli klar till årsskiftet.)

Off label en fråga också för EU-kommissionen När och hur är off label-användning ok. Åsikterna skiftar mellan EU-länder och inom Sverige.
lakemedelsvarlden.se 13.10.2016
När och hur är off label-användning ok. Åsikterna skiftar mellan EU-länder och inom Sverige.

Off label-förskrivning är ett hett ämne, såväl inom EU som i Sverige. En rapport i ämnet som EU-kommissionen arbetar med är två år försenad, men förväntas bli klar till årsskiftet.

Och här hemma har TLV stött på motstånd när man vill sätta på pränt det myndigheten redan säger sig ha som praxis; att ibland använda läkemedel som saknar marknadsföringsgodkännande för indikationen som jämförelse vid subventionsbeslut. Det kan vara aktuellt om det inte godkända läkemedlet har en ”ej obetydlig” användning och överensstämmer med vetenskap och beprövad erfarenhet. (...)

I fallet Mabthera hade Socialstyrelsen och Läkemedelsverket hamnat på kollisionskurs om läkemedlet kommit med som en rekommenderad läkemedelsbehandling. Strykningen kanske kan ses som ett resultat av den arbetsgrupp som de två myndigheterna har för att hitta arbetssätt som möjliggör ett samstämmigt budskap när det handlar om läkemedelsbehandlingar. (...)

Off label-diskussionen inom EU-kommissionen handlar om att först komma överens om det finns ett behov av att koordinera användningen på EU-nivå och om man i så fall ska ta fram riktlinjer för det. (...)

(Anm: Legemiddelkonsulenter forteller leger lite om sideeffekter, ifølge studie. (Drug Reps Tell Docs Little of Side Effects: Survey) (Journal of General Internal Medicine 2013 (April).)

(Anm: Interessekonflikter vanlig blant forfattere av amerikanske retningslinjer for kreft, ifølge studie. (Conflicts of interest common among US cancer guideline authors, study finds.) BMJ 2016;354:i4660 (Published 25 August 2016).)

(Anm: Selgere i kirurgenes rekker: Relasjoner mellom kirurger og medisinske utstyrsrepresentanter (Salespeople in the Surgical Suite: Relationships between Surgeons and Medical Device Representatives. PLoS ONE 11(8): e0158510).

(Anm: - Nesten ni av 10 leger og forskere som bidro til å utvikle et førende sett med retningslinjer for kreftomsorgen i USA rapporterte finansielle bånd til legemiddelindustrien og medisinske utstyrsfirmaer). (medicalnewstoday.com 30.8.2016).)

(Anm: Ingen gratis lunsj for leger: Sponsede måltider knyttet til flere resepter (No free lunch for docs: Sponsored meals linked to more prescriptions) (mmm-online.com 20.6.2016).)

(Anm: Amerikansk statsadvokat undersøger forhold omkring Lundbeck-middel. En amerikansk statsadvokat har indledt en undersøgelse om blandt andet salg og marketing af Lundbecks Xenazine til behandling af Huntingtons sygdom. (medwatch.dk 10.2.2016).)

- Forskrivning utenfor preparatomtale ("off label") (utenfor indikasjon) for barn og ungdom er utbredt i USA. Vår studie reiser spørsmål om potensielt misbruk av atypiske antipsykotika (AAP) i befolkningen.

National trends in off-label use of atypical antipsychotics in children and adolescents in the United States.
Medicine (Baltimore). 2016 Jun;95(23):e3784.
Abstract The objectives of the study were as follows: to examine the national trend of pediatric atypical antipsychotic (AAP) use in the United States; to identify primary mental disorders associated with AAPs; to estimate the strength of independent associations between patient/provider characteristics and AAP use. Data are from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. First, average AAP prescription rates among 4 and 18-year-old patients between 1993 and 2010 were estimated. Second, data from 2007 to 2010 were combined and analyzed to identify primary mental disorders related to AAP prescription. Third, a multivariate logistic regression model was developed having the presence of AAP prescription as the dependent variable and patient/provider characteristics as explanatory variables. Adjusted odds ratios (AORs) with associated 95% confidence intervals (CIs) were estimated. Outpatient visits including an AAP prescription among 4 to 18-year-old patients significantly increased between 1993 and 2010 in the United States, and over 65% of those visits did not have diagnoses for US Food and Drug Administration-approved AAP indications. During 2007 to 2010, the most common mental disorder was attention-deficit hyperactivity disorder, accounting for 24% of total pediatric AAP visits. Among visits with attention-deficit hyperactivity disorder diagnosis, those with Medicaid as payer (AOR 1.66, 95% CI 1.01-2.75), comorbid mental disorders (e.g., psychoses AOR 3.34, 95% CI 1.35-8.26), and multiple prescriptions (4 or more prescriptions AOR 4.48, 95% CI 2.08-9.64) were more likely to have an AAP prescription. The off-label use of AAPs in children and adolescents is prevalent in the United States. Our study raises questions about the potential misuse of AAPs in the population. (…)

(Anm: Psychiatrist is charged after 12 patient deaths. A psychiatrist from Atlanta, Georgia, has been charged with prescribing pain drugs outside the usual course of professional practice after 12 of his patients died from drug overdoses. BMJ 2016;352:i534 (Published 27 January 2016).)

(Anm: Lif advarer mod organiseret off-label-brug. Hos lægemiddelindustrien er man stærkt imod brugen af off-label-medicin i større stil, fordi man mener, det truer patientsikkerheden og undergraver det godkendelsessystem, som industrien er underlagt. (medwatch.dk 17.3.2016).)

(Anm: Off-label use of the expensive orphan drug eculizumab in France 2009–2013 and the impact of literature: focus on the transplantation field. (…) Conclusion Eculizumab started being notably used for off-label indications in France since the end of 2011, and this use increased until the end of the study. We found only low-level evidence concerning the off-label use of eculizumab in the transplantation field through the studied period. Eur J Clin Pharmacol (2016) 72: 737).)

(Anm: Antidepressants v cognitive behavioural therapies. Patients in trials of antidepressants are not typical of those in everyday practice. BMJ 2016;352:i577 (Published 10 February 2016).)

(Anm: Kåre Schultz: ”Det er spørgsmålet, om man tør”. Det er slut med nye samarbejdsaftaler for Lundbeck, der fremover vil selv og i fremtiden kun vil vokse organisk. Sådan lyder den nye strategi fra topchef Kåre Schultz, der trækker på sine erfaringer fra Novo Nordisk. (medwatch.dk 10.2.2016).)

(Anm: Legemiddelreklame (legemiddelinformasjon) (mintankesmie.no).)

(Anm: Drug Promotion in the 21st Century: Off-label Marketing and First Amendment Concerns (fdalawblog.net 23.3.2016).)

(Anm: Delirium is associated with 5-fold increased mortality in acute cardiac patients. (medicalnewstoday.com 16.3.2017).)

(Anm: Lager dokumentarfilm om legemiddelindustrien og psykofarmaka. Filmskaper Annikken Hoel vil ha svar på hvorfor søsteren plutselig døde. (Dødsårsak ukjent). (tv.nrk.no/serie/dagsrevyen 13.3.2017).)

(Anm: «Dødsårsak: ukjent»: Bør bli pensum for både leger og lekfolk. Viktig og skremmende om legemiddelindustriens makt. (...) Det er klart at regissøren har en agenda. Hun dveler ikke ved konspirasjonsteorier, men forsøker å finne frem til en sannhet. Det er klart at regissøren har en agenda. Hun dveler ikke ved konspirasjonsteorier, men forsøker å finne frem til en sannhet. Samtidig er mye av informasjonen i filmen kjent dersom du har fulgt med på store søksmål i USA. Hun greier likevel å få frem et oversiktlig og skremmende bilde av de sterke og korrupte båndene som eksisterer mellom politikere, byråkrater og de store farmasøytiske selskapene. (aftenposten.no 22.3.2017).)

(Anm: Norsk dokumentar: «Lykkepillen» Ti år i psykiatrien var som ti år med tortur for Silje Marie. Et møte med en sykepleier endret alt. (aftenposten.no 13.3.2017).)

(Anm: Uten obduksjoner begraver sykehusene feilene sine. (Without Autopsies, Hospitals Bury Their Mistakes) (…) Da Renee Royak-Schaler uventet kollapset og døde 22. mai beordret ingen obduksjon. (…) Diagnostiske feil, som studier viser er vanlig, forblir uoppdaget, og tillater at leger kan fortsette sin praksis på andre pasienter med en falsk følelse av trygghet. (…) Mulighetene for å lære om effektiviteten av medisinske behandlinger og progresjon av sykdommer går tapt. Unøyaktig informasjon ender opp i dødsattester, og undergraver påliteligheten for avgjørende helsestatistikk. (propublica.org 15.12.2011).)

- Lægers off-label brug af nye kræftbehandlinger er uden effekt

Lægers off-label brug af nye kræftbehandlinger er uden effekt
dagpharmatimes.com 22.9.2015
Det hjælper ikke på kræftpatienters overlevelse, at læger er begyndt at udskrive nye individualiserede kræftlægemidler off-label, konkluderer forskergruppe i Lancet Oncology.

Lægernes off-label brug af nye individualiserede kræftbehandlinger løber forud for den videnskabelige viden. Det konkluderer en gruppe franske forskere i et randomiseret studie, som er publiceret i Lancet Oncology. I takt med at prisen på genetisk sekventering falder, begynder onkologer verden over at udskrive dyre lægemidler baseret på patienternes genetiske profiler, selvom lægemidlerne endnu ikke […]

- Syke risikerer å bli forskrevet legemidler som ikke er godkjent for deres sykdom

Syge risikerer forkert medicin
dr.dk 19.10.2009
Syge danskere risikerer at få udskrevet medicin, som slet ikke er godkendt til deres sygdom, og som derfor kan være direkte farlig for dem.

Firmaer i medicinal-branchen bliver gang på gang taget i at forsøge at overtale læger til at udskrive firmaernes præparater til flere patientgrupper, end medicinen er godkendt til.

Det er i strid med loven og et resultat af en benhård konkurrence om milliarderne i medicinal- branchen.

- Det er dybt bekymrende og har karakter af korruption, siger Peter Gøtzsche til DR Nyheder. Han er overlæge, medlem af foreningen Læger uden sponsor og han har i lang tid fulgt medicinalindustriens markedssføringsmetoder. (...)

(Anm: Peter Gøtzsche: »Én mand kan godt ændre videnskaben«. Han har sammenlignet medicinalindustrien med Hitlerjugend og har fået en stor del af den danske psykiaterstab på nakken, da han for nylig udgav bogen ’Dødelig psykiatri og organiseret fornægtelse’. Mød Peter Gøtzsche; internationalt anerkendt professor, som ikke er bange for at være udiplomatisk. (videnskab.dk 13.11.2015).)

(Anm: Alzheimers sykdom og andre årsaker til demens. (mintankesmie.no).)

(Anm: Medisinering av psykisk utviklingshemmede (Lørdagsrevyen 12.11.2011).)

(Anm: Tror psykose­medisin tok livet av Renate. Da søsteren til Anniken Hoel døde brått, sto familien uten svar. Til det viste seg at «plutselig død» var en mulig bivirkning av medisinene hun tok. (nrk.no 13.3.2017).)

(Anm: Overmedisinering av eldre (NRK Dagsrevyen) (…) Flere eldre dør av overmedisinering. (...) Vi er kommet dit at vi aksepterer lettere at pasienter dør av bivirkninger av medisiner enn av selve sykdommen. (nrk.no 10.2.2017).)

(Anm: Moren (85) ble syk av behandlingen på sykehjem: – Hadde ikke forventet at de skulle ødelegge et menneske med medisiner. Beboere på norske sykehjem bruker i gjennomsnitt syv medikamenter hver, viser tall fra Regjeringens demensplan 2020. Ofte er tallet mye høyere. (tv2.no 18.5.2017.)

(Anm: Han blei medisinert til døde (nrk.no 12.11.2011).)

(Anm: Havarikommisjoner (undersøkelseskommisjoner) (mintankesmie.no).)

(Anm: Bruk av annengenerasjons antipsykotiske legemidler øker parametre for metabolsk syndrom. (dgnews.docguide.com 17.3.2016).)

- Studien viser sammenhengen mellom metabolsk syndrom og risiko for kognitive sykdommer.

(Anm: Study shows link between metabolic syndrome and risk of cognitive disorders. A study presented at the European Academy of Neurology Congress in Amsterdam has shown that obesity alone is not a risk factor for cognitive disorders, but commonly associated co-morbidities such as diabetes, high blood pressure, and metabolic disorders are. Dementia diseases in patients who suffer from diabetes are often treated inadequately, a new research paper reveals. It has long been supposed that patients with metabolic syndrome are more likely to suffer from cognitive impairment - and to a greater extent. Reasons are thought to include chronic inflammatory processes which can induce neuroinflammatory and neurodegenerative changes. Whether obese individuals without risk factors such as diabetes mellitus, metabolic disorders and the presence of albumin in the urine have an increased risk of cognitive impairment is still little researched. (news-medical.net 27.6.2017).)

(Anm: Consider the Evidence Before Prescribing Antidepressants Off-Label. (…) For only a few depression medications does strong evidence support use for nondepression indications. A recent study showed that about half of antidepressants prescribed by Quebec primary care clinicians were for off-label, nondepression indications, such as anxiety, pain, and insomnia (NEJM JW Gen Med Jul 1 2016 and JAMA 2016; 315:2230). Now, the same researchers analyzed this data set again to investigate the frequency of, and scientific evidence supporting, off-label antidepressant prescriptions. NEJM 2017 (March 23, 2017).)  

(Anm: Metabolic Syndrome Components Are Associated With Symptomatic Polyneuropathy Independent of Glycemic Status. Diabetes Care 2016 (Published online before print March 10, 2016).)

(Anm: Patients With Polyneuropathy Receive Long-Term Opioid Therapy, No Clear Benefit. CHICAGO -- May 23, 2017 -- Polyneuropathy is associated with an increased likelihood of long-term opioid therapy, but therapy does not appear to improve functional status, according to a study published online by JAMA Neurology. Polyneuropathy is a common painful condition, especially among older patients, which can result in functional impairment. (dgnews.docguide.com 23.5.2017).)

(Anm: Prepsychosis links with elevated metabolic syndrome. MADRID – Untreated people at high risk for developing psychosis also showed an increased prevalence of certain components of metabolic syndrome in data collected from 163 German study participants, a finding that gives new insight into the well-documented but poorly delineated link between schizophrenia and metabolic syndrome. (...) He also suggested prescribing antipsychotic medications that pose the lowest risk for causing further metabolic derangements in patients. (clinicalpsychiatrynews.com.com 2.4.2016).)

(Anm: Joachim Raese, MD. Metabolic syndrome is defined by the aggregation of hypertriglyceridemia, low high-density lipoprotein (HDL) levels, elevated fasting glucose, hypertension, and increased waist circumference. Metabolic syndrome confers an increased risk of developing diabetes and of dying from coronary artery disease. Cardiovascular disease is the leading cause of death among patients with schizophrenia, who have a life expectancy about 20 years shorter than the general population. (…) For a more detailed discussion, I suggest watching a YouTube video that we have prepared. (cmeinstitute.com 27.4.2016).)

(Anm: Video Lecture 8: Metabolic Syndrome Lectures 1 (By Dr. Joachim Raese) (youtube.com).)

(Anm: - Lege får 30 år til livstid for drap i sak i L.A. knyttet til pasienters overdoser. (Doctor gets 30 years to life for murders in L.A. case tied to patients' overdoses.) (…) En dommer dømte fredag en lege i Rowland Height til 30 år til livstid i fengsel for drapene på tre av sine pasienter som følge av dødelig overdose, en dom som satte sluttstrek i en "landmark"-sak som enkelte medisinske eksperter sier kan endre hvordan leger i hele landet håndterer forskrivningen av reseptbelagte legemidler. (latimes.com 5.2.2016).)

(Anm: Diskriminering, feilmedisineringer hos mennesker med utviklingshemming og utfordrende atferd (psykofarmaka; antidepressiva, antipsykotika, sovemedisiner) etc. (mintankesmie.no).)

(Anm: På tide å revurdere? (Time to rethink?) Legemiddelbehandlinger hos mennesker med utviklingshemming og utfordrende atferd (Drug treatments in people with intellectual disability and challenging behaviour disabilities) Editorials (Lederartikkel) BMJ 2014;349:g4323 (Published 04 July 2014).)

(Anm: - Slår sovepiller os ihjel? (- Studiet er det største af sin slags på globalt plan og har også undersøgt sammenhængen mellem brug af antidepressiver og antipsykotika og dødelighed. Også her fandt forskerne en overdødelighed.) (videnskab.dk 21.3.2016).)

(Anm: Ökad övervakning av off label-förskrivning - Med nya IT-verktyg har danskarna bland annat upptäckt lungfibros orsakad av off label-användning. (lakemedelsvarlden.se 6.2.2015).)

(Anm: Off-label prescriptions frequently cause adverse events. Off-label prescribing of drugs is common and very likely to cause adverse events, particularly when no strong scientific evidence supports the off-label use, according to a report published online Nov. 2 in JAMA Internal Medicine. (…) Moreover, the incidence of adverse events was 54% higher for off-label use unsupported by strong scientific evidence (21.7 per 10,000 person-months) than for off-label use supported by strong scientific evidence (13.2 per 10,000 person-months) (…) (clinicalpsychiatrynews.com 4.11.2015).)

(Anm: Association of Off-Label Drug Use and Adverse Drug Events in an Adult Population. (…) Conclusions and Relevance  Off-label use of prescription drugs is associated with ADEs. Caution should be exercised in prescribing drugs for off-label uses that lack strong scientific evidence. Future electronic health records should be designed to enable postmarket surveillance of treatment indications and treatment outcomes to monitor the safety of on- and off-label uses of drugs.JAMA Intern Med. 2015 (Published online November 02, 2015).)

- Ingen bevis støtter forskrivning av atypiske antipsykotika utenfor preparatomtale

No Evidence to Support Many Off-label Uses of Atypical Antipsychotics (Ingen bevis støtter forskrivning av atypiske antipsykotika utenfor preparatomtale)
newswise.com 18.1.2007
Newswise — Enkelte nyere antipsykotika godkjent for å behandle schizofreni og bipolar lidelse blir foreskrevet til millioner av amerikanere for depresjon, demens og andre psykiske lidelser uten sterke bevis for at denne type forskrivning utenfor preparatromtale (off-label) er effektiv, ifølge en ny analyse av HHS' Agency for Healthcare Research and Quality". (...) (— Some newer antipsychotic medications approved to treat schizophrenia and bipolar disorder are being prescribed to millions of Americans for depression, dementia, and other psychiatric disorders without strong evidence that such off-label uses are effective, according to a new analysis by HHS’ Agency for Healthcare Research and Quality.)

Rapporten offentliggjort i dag, Efficacy and Comparative Effectiveness of Off-Label Use of Atypical Antipsychotics (Effekt og sammenlignende effekt av forskrivning utenfor preparatromtale (off-label) av atypiske antipsykotika), er den nyeste analyse fra AHRQs sitt Effective Health Care program. Dette programmet representerer den første statlige innsats for å sammenligne alternative behandlinger for betydelige helsemessige forhold og gjøre funnene offentlig tilgjengelige. Programmet er ment å hjelpe pasienter, leger, sykepleiere og andre til å velge de mest effektive behandlinger. Informasjon om programmet, inkludert fullstendige rapporter, kan bli funnet på http://www.effectivehealthcare.ahrq.gov. (...) (The report released today, Efficacy and Comparative Effectiveness of Off-Label Use of Atypical Antipsychotics, is the newest analysis from AHRQ's Effective Health Care program. That program represents the first federal effort to compare alternative treatments for significant health conditions and make the findings public. The program is intended to help patients, doctors, nurses, and others choose the most effective treatments. Information on the program, including full reports, can be found at http://www.effectivehealthcare.ahrq.gov.)

(Anm: Medisinering av psykisk utviklingshemmede (Lørdagsrevyen 12.11.2011).)

(Anm: Tror psykose­medisin tok livet av Renate. Da søsteren til Anniken Hoel døde brått, sto familien uten svar. Til det viste seg at «plutselig død» var en mulig bivirkning av medisinene hun tok. (nrk.no 13.3.2017).)

(Anm: Overmedisinering av eldre (NRK Dagsrevyen) (…) Flere eldre dør av overmedisinering. (...) Vi er kommet dit at vi aksepterer lettere at pasienter dør av bivirkninger av medisiner enn av selve sykdommen. (nrk.no 10.2.2017).)

(Anm: Moren (85) ble syk av behandlingen på sykehjem: – Hadde ikke forventet at de skulle ødelegge et menneske med medisiner. Beboere på norske sykehjem bruker i gjennomsnitt syv medikamenter hver, viser tall fra Regjeringens demensplan 2020. Ofte er tallet mye høyere. (tv2.no 18.5.2017.)

(Anm: Han blei medisinert til døde (nrk.no 12.11.2011).)

(Anm: Havarikommisjoner (undersøkelseskommisjoner) (mintankesmie.no).)

(Anm: Bruk av annengenerasjons antipsykotiske legemidler øker parametre for metabolsk syndrom. (dgnews.docguide.com 17.3.2016).)

- Studien viser sammenhengen mellom metabolsk syndrom og risiko for kognitive sykdommer.

(Anm: Study shows link between metabolic syndrome and risk of cognitive disorders. A study presented at the European Academy of Neurology Congress in Amsterdam has shown that obesity alone is not a risk factor for cognitive disorders, but commonly associated co-morbidities such as diabetes, high blood pressure, and metabolic disorders are. Dementia diseases in patients who suffer from diabetes are often treated inadequately, a new research paper reveals. It has long been supposed that patients with metabolic syndrome are more likely to suffer from cognitive impairment - and to a greater extent. Reasons are thought to include chronic inflammatory processes which can induce neuroinflammatory and neurodegenerative changes. Whether obese individuals without risk factors such as diabetes mellitus, metabolic disorders and the presence of albumin in the urine have an increased risk of cognitive impairment is still little researched. (news-medical.net 27.6.2017).)

(Anm: Metabolic Syndrome Components Are Associated With Symptomatic Polyneuropathy Independent of Glycemic Status. Diabetes Care 2016 (Published online before print March 10, 2016).)

(Anm: Patients With Polyneuropathy Receive Long-Term Opioid Therapy, No Clear Benefit. CHICAGO -- May 23, 2017 -- Polyneuropathy is associated with an increased likelihood of long-term opioid therapy, but therapy does not appear to improve functional status, according to a study published online by JAMA Neurology. Polyneuropathy is a common painful condition, especially among older patients, which can result in functional impairment. (dgnews.docguide.com 23.5.2017).)

(Anm: Prepsychosis links with elevated metabolic syndrome. MADRID – Untreated people at high risk for developing psychosis also showed an increased prevalence of certain components of metabolic syndrome in data collected from 163 German study participants, a finding that gives new insight into the well-documented but poorly delineated link between schizophrenia and metabolic syndrome. (...) He also suggested prescribing antipsychotic medications that pose the lowest risk for causing further metabolic derangements in patients. (clinicalpsychiatrynews.com.com 2.4.2016).)

(Anm: Joachim Raese, MD. Metabolic syndrome is defined by the aggregation of hypertriglyceridemia, low high-density lipoprotein (HDL) levels, elevated fasting glucose, hypertension, and increased waist circumference. Metabolic syndrome confers an increased risk of developing diabetes and of dying from coronary artery disease. Cardiovascular disease is the leading cause of death among patients with schizophrenia, who have a life expectancy about 20 years shorter than the general population. (…) For a more detailed discussion, I suggest watching a YouTube video that we have prepared. (cmeinstitute.com 27.4.2016).)

(Anm: Video Lecture 8: Metabolic Syndrome Lectures 1 (By Dr. Joachim Raese) (youtube.com).)

(Anm: - Lege får 30 år til livstid for drap i sak i L.A. knyttet til pasienters overdoser. (Doctor gets 30 years to life for murders in L.A. case tied to patients' overdoses.) (…) En dommer dømte fredag en lege i Rowland Height til 30 år til livstid i fengsel for drapene på tre av sine pasienter som følge av dødelig overdose, en dom som satte sluttstrek i en "landmark"-sak som enkelte medisinske eksperter sier kan endre hvordan leger i hele landet håndterer forskrivningen av reseptbelagte legemidler. (latimes.com 5.2.2016).)

(Anm: Diskriminering, feilmedisineringer hos mennesker med utviklingshemming og utfordrende atferd (psykofarmaka; antidepressiva, antipsykotika, sovemedisiner) etc. (mintankesmie.no).)

(Anm: På tide å revurdere? (Time to rethink?) Legemiddelbehandlinger hos mennesker med utviklingshemming og utfordrende atferd (Drug treatments in people with intellectual disability and challenging behaviour disabilities) Editorials (Lederartikkel) BMJ 2014;349:g4323 (Published 04 July 2014).)

(Anm: - Slår sovepiller os ihjel? (- Studiet er det største af sin slags på globalt plan og har også undersøgt sammenhængen mellem brug af antidepressiver og antipsykotika og dødelighed. Også her fandt forskerne en overdødelighed.) (videnskab.dk 21.3.2016).)

(Anm: Clinician Summary – Aug. 1, 2012 Off-Label Use of Atypical Antipsychotics: An Update - Clinician Summary – Aug. 1, 2012 (effectivehealthcare.ahrq.gov).)

(Anm: Antipsykotika (psykofarmaka etc.) (mintankesmie.no).)

(Anm: Lægemiddelstyrelsen opfordrer læger til at være opmærksomme på disse alvorlige bivirkninger hos børn og unge i behandling med aripiprazol (Abilify) (…) Gennemgangen viser også, at børn med ASD (autisme) der behandles med aripiprazol, kan udvikle alvorlige psykiatriske bivirkninger såsom svære kroniske søvnproblemer, aggressiv adfærd og hallucinationer. (…) Hårtab, depression og psykose, Vægtøgning, Hypercholesterolemi, Hypercholesterolemi. (LÆGEMIDDELSTYRELSEN - NYT OM BIVIRKNINGER 2016;7(9).)

(Anm: «Psykiatrien i Norge har hatt for svak ledelse. På alle nivåer. I alle år». KRONIKK: Helseminister Bent Høie (H). BENT HØIE, Helseminister. (vg.no 23.11.2016).)

(Anm: - Kan vi stole på forskningen? (...) - Er det ikke så nøye med sannheten fordi det lønner seg økonomisk og er lettvint bare å tro på forenklingene, halvsannhetene og de opplagt bløffene? (...) - Trass i all forskning. Trass i alle milliarder av kroner som var blitt investert, trass i alle gode intensjoner. Men «sannheten om de psykiske sykdommers natur, ubalansen i hjernens kjemi» viste seg etter hvert ikke å være sann. (dagensmedisin.no 2.4.20

(Anm: Dyremodeller åbner døren til ny generation af antipsykotika. (- »Industrien har måttet erkende, at de ‘varer’, der var på hylderne, ikke var brugbare. (dagensmedicin.dk 31.3.2017).)

(Anm: Psykofarmaka dreper mange. (…) I DAGENS MEDISIN 12. februar hevder psykiaterne Rune Andreas Kroken og Erik Johnsen at det ikke er riktig at psykiatrisk behandling tar liv. De påstår til og med at man lever lenger dersom man får antipsykotika. Dette er helt utrolig.) (dagensmedisin.no 10.3.2017).)

(Anm: Få pasienter kjenner til klageordning. (…) Søkere fikk medhold i en firedel av sakene. For dem som klaget på legemiddelskader utløst av antipsykotika, fikk imidlertid kun 9,4% medhold. - Man kan spekulere i om pasienter som ikke er flinke nok til å snakke om sin sak, ikke når frem. (Tidsskr Nor Legeforen 22.1.2013).)

(Anm: Høie om psykiatrien: Har fått leve sitt eget liv. (...) Dette er veldig alvorlig, og bekrefter dessverre det inntrykket jeg har fått om tvangsbruken innen psykisk helse: at den går langt utover det som er hensikten og det juridiske grunnlaget - og at den går utover det som er god faglighet, sier Høie til VG. (vg.no 20.11.2016).)

(Anm: 50.000 nordmenn vil utvikle schizofreni i løpet av livet. - De som lider av denne psykoselidelsen har tanker om verden som ikke stemmer, sier ekspert. (…) Uklare symptomer i starten. Symptomer på Schizofreni utvikler seg over tid, og er i starten litt uklare. Ofte blir de mer fremtredende etter hvert. - Da vises blant annet sosial tilbaketrekning, man mister kontakt med virkeligheten, har vrangforestillinger, hallusinasjoner, tap av matlyst og tap av hygiene. Det er store individuelle variasjoner og mange opplever det som en berg- og dalbane, sier Tove Gundersen, som er generalsekretær i Rådet for psykisk helse. (kk.no 26.9.2016).)

(Anm: Katteparasitt kan gi schizofreni og tvangslidelser. Forskere har funnet en sammenheng mellom katteparasitten Toxoplasma gondii og utviklingen av forskjellige psykiske lidelser hos mennesker. (…) En parasitt fra katteavføring, T. gondii, kan sette fast seg i menneskehjernen og føre til schizofreni, manisk depressiv sinnslidelse, avhengighet og tvangstanker. (nrk.no 29.6.2015).)

(Anm: No, Your Cat Isn't a Threat to Your Mental Health. (…) But mental health worries aside, pregnant women should still be cautious about exposure to cat litter boxes, another researcher warned. "There is good evidence that T. gondii exposure during pregnancy can lead to serious birth defects and other health problems in children," said study senior author Dr. James Kirkbride. (medicinenet.com 21.2.2017).)

(Anm: Angstbehandling spres til utlandet. Her er nederlandske psykologer i Bergen for å lære om behandlingen som kan kurere tvangstanker på fire dager. Nå spres behandlingsopplegget til andre sykdommer og utover Norges grenser. (dagensmedisin.no 21.12.2016).)

(Anm: Schizofreni kopplas till TBE-smitta. Det kan finnas en koppling mellan virusinfektioner som TBE och neuropsykiatriska sjukdomar som schizofreni. Det har svenska forskare kommit fram till i en studie som presenterades på en konferens i San Diego på måndagen. (svd.se 6.11.2007).)

(Anm: Scientists find chemical pathway responsible for schizophrenia symptoms. Recent studies have suggested that kynurenic acid (KYNA) plays a key role in the pathophysiology of schizophrenia. People with schizophrenia have been shown to possess higher levels of KYNA than healthy individuals. KYNA helps to metabolize tryptophan - an essential amino acid that, in turn, helps the body to produce the "happiness" neurotransmitter serotonin, and the vitamin niacin. (medicalnewstoday.com 9.2.2017).)

(Anm: Psykose. Alle mennesker kan utvikle psykose. - Balansegangen mellom opplevd stress og ballast til å stå imot, er avgjørende, forteller psykiater. (…) - Stress er et sentralt tema. For eksempel har vi forskjellige måter å takle en belastende hendelse på jobb på. (…) - Man kan kalle det en forvirringstilstand, selv om heller ikke det er helt dekkende. (…) Symptomer ved psykose. Tidlige tegn kan være at man: (…) - Det er en kjempebelastning å ha en psykose. Mange blir redde og opplever ting de ikke forstår. Man vet at noen mennesker kan få tanker og impulser om å ta sitt eget liv, legger hun til. (lommelegen.no 13.6.2016).)

(Anm: Samtaleterapi styrker hjernens forbindelser for behandling av psykose. (Talk therapy strengthens brain connections to treat psychosis. Cognitive behavior therapy is used to help treat a number of mental health conditions, including anxiety, depression, and post-traumatic stress disorder. For the first time, researchers have shown how this type of therapy triggers brain changes to produce long-term benefits for patients with psycosis. Researchers have found evidence to suggest that talk therapy can alter the brain in a way that leads to long-term recovery from psychosis. Lead study author Dr. Liam Mason, of King's College London in the United Kingdom, and colleagues report their findings in the journal Translational Psychiatry.) (medicalnewstoday.com 22.1.2017).)

(Anm: Forskningen på schizofreni og psykose er i dyp krise | Paul Møller, dr. med. og spesialist i psykiatri. Hjernen kan måles, veies og avbildes eksakt og detaljert. Psyken er derimot subjektiv, flytende, flyktig og abstrakt, og derfor langt mer krevende å forske på. (aftenposten.no 26.1.2017).)

(Anm: Fem myter om schizofreni | Bjørn Rishovd Rund, professor, Psykologisk institutt, Universitetet i Oslo Fem myter om schizofreni. Begrepet schizofreni er sterkt belastet. Det skyldes til dels noen myter som er vanskelige å knekke. Bjørn Rishovd Rund professor, Psykologisk institutt, Universitetet i Oslo (aftenposten.no 5.2.2017).)

(Anm: Det vakreste mennesket jeg kjenner, har diagnosen schizofreni. Likevel kaller du ham gal | Karoline Kongshaug (aftenposten.no 29.6.2017).)

(Anm: Probiotics may help treat yeast infections, bowel problems in men with schizophrenia. The findings, published in the May 1 issue of Brain, Behavior, and Immunity, support growing evidence of close links between the mind and the gut. (…) The commercially available probiotic contained over 1 billion colony-forming units of Lactobacillus rhamnosus and Bifidobacterium animalis in each pill. PANSS scores were reassessed every two weeks, and the participants self-reported on the ease of their bowel movements weekly on a scale of 0 to 4. At the end of the study, the researchers collected another blood sample. Using the blood samples, the researchers measured antibody levels to yeast Saccharomyces cerevisiae, known as brewer's yeast, and Candida albicans, known to cause yeast infections, before and after the probiotic treatment. Both types of yeast are elevated in people with schizophrenia. (news-medical.net 5.4.2017).)

(Anm: Psychosis: Link to brain inflammation antibodies raises new treatment hope. For the first time, researchers reveal that some people presenting with a first episode of psychosis have specific antibodies in their blood. The antibodies are the same ones known to cause encephalitis or brain inflammation. The discovery raises the question of whether the removal of these antibodies could be an effective treatment for psychosis as it is for encephalitis. The researchers - led by Belinda R. Lennox, a professor in the department of psychiatry at the University of Oxford in the United Kingdom - report their findings in The Lancet Psychiatry. (…) Previous studies have already fueled discussion about the role antibodies targeting neural proteins may play in psychosis. For example, a study reported in 2015 of children experiencing their first episode of psychosis, also found links to an antibody response to NMDAR. (medicalnewstoday.com 9.12.2016).)

(Anm: Psykose som målestokk for tvungent psykisk helsevern. Sammendrag Abstract  Denne artikkelen handlar om vilkåra for tvungent psykisk helsevern. Det er særleg fokusert på ei drøfting omkring det såkalla hovudvilkåret etter lov om psykisk helsevern (phvl.) § 3-3 (1) nr. 3. I artikkelen vert det drøfta om dagens rettsregel og dei vurderingstema den set opp, gjer ei god avgrensing sett i høve til føremåla med tvungent psykisk helsevern. Det vert òg skissert ei betre løysing for tolking av vilkåret. Kritisk juss03 / 2016 (Volum 2) Side: 217-237DOI: 10.18261/issn.2387-4546-2016-03-03.)

(Anm: Psykose forbundet med lave nivåer av fysisk aktivitet. (Psychosis associated with low levels of physical activity. A large international study of more than 200,000 people in nearly 50 countries has revealed that people with psychosis engage in low levels of physical activity, and men with psychosis are over two times more likely to miss global activity targets compared to people without the illness.) (medicalnewstoday.com 26.8.2016).)

(Anm: Antipsykotika og fysisk attraktivitet (Antipsychotics and physical attractiveness) (...) Antipsykotika, som gruppe, fører til vektøkning og kan føre til munntørrhet og dårlig ånde, grå stær, hirsutisme (uvanleg sterk eller altfor utbreidd hårvekst (helst hos kvinner)), akne og stemmeendringer; de kan forstyrre symmetri av gangart og øke risikoen for tics og spasmer og inkontinens, og potensielt undergrave en persons attraktivitet. Clin Schizophr Relat Psychoses. 2011 Oct;5(3):142-146.)

(Anm: Medikamentutløst dystoni. (…) Videoen illustrerer ekstrapyramidale bivirkninger med dystoni i tunge og kjeveområdet. Tidsskr Nor Legeforen 2016; 136:1730-1730 (8.11.2016).)

(Anm: Association of anticholinergic burden with adverse effects in older people with intellectual disabilities: an observational cross-sectional study. Conclusions Older people with intellectual disabilities and with mental health conditions were exposed to high anticholinergic burden. This was associated with daytime dozing and constipation. The British Journal of Psychiatry Dec 2016, 209 (6) 504-510.)

(Anm: Bivirkninger av antipsykotika - Related Editorial (Relatert lederartikkel) (…) Bruken av antipsykotika innebærer en vanskelig avveining mellom nytte for å lindre psykotiske symptomer og noen ganger risikoen for problematiske bivirkninger som forkorter levetiden. (…) Alle antipsykotika er forbundet med en økt sannsynlighet for sedasjon, seksuell dysfunksjon, postural hypotensjon, hjertearytmi og plutselig hjertedød. (…) Antikolinerge effekter inkluderer forstoppelse, urinretensjon, tørr munn, uklart syn og, til tider, kognitiv svekkelse. Disse symptomene kan føre til andre problemer som tannforråtnelse, fall eller gastrointestinal obstruksjon. Am Fam Physician. 2010 Mar 1;81(5):617-622).)

(Anm: J&J’s Janssen dømt til å betale 70 millioner dollar i Risperdal-rettssak. (J&J's Janssen hit with $70 mln verdict in Risperdal trial) (…) Juryen i Philadelphia Court of Common Pleas fant at firmaet mislyktes å advare guttens helsepersonell om risikoen for gynecomastia, som er brystvekst hos menn eller gutter forårsaket av en hormonell ubalanse, og at de med vilje forfalsket, og ødela eller skjulte bevis i saken.) Janssen dømt til å betale 70 millioner dollar i Risperdal-rettssak. (finance.yahoo.com 1.7.2016).)

(Anm: J&J's Janssen hit with $70 million verdict in Risperdal trial. Johnson & Johnson and Janssen are facing more than 12,000 claims over Risperdal, according to Johnson & Johnson's most recent quarterly report. (…) In 2013, Johnson & Johnson and Janssen paid more than $2.2 billion to resolve civil and criminal investigations by the U.S. Department of Justice into its marketing of Risperdal and several other drugs. (reuters.com 1.7.2016).)

(Anm: Jury smacks J&J with $70M in damages in latest Risperdal breast case. Johnson & Johnson ($JNJ) is fighting more than 1,500 legal claims that its antipsychotic Risperdal triggered breast development in boys, and the company has landed on the wrong side of a jury verdict in several of them so far. (fiercepharma.com 5.7.2016).)

(Anm: Antipsykotika forårsaker ansiktsgrimasering og andre typer mulige varige hjerneskader (mintankesmie.no).)

(Anm: Derfor bliver man fed af antipsykotisk medicin. (- Derfor blir man feit av antipsykotika.) (videnskab.dk 7.1.2016).)

(Anm: Signaling from dysfunctional mitochondria induces a distinct type of senescence. (Signalering fra dysfunksjonelle mitokondrier induserer en distinkt type tiltagende alderdom.) Finding provides alternative explanation for the free-radical theory of aging and suggests new role for mitochondria in affecting physiology. (medicalnewstoday.com 11.12.2015).)

(Anm: Mitochondrial Dysfunction Meets Senescence. Trends Biochem Sci. 2016 Feb 10. pii: S0968-0004(16)00020-7. [Epub ahead of print].)

(Anm: NTNU-forskere er med i teamet: Har laget «smart» speil som kan avsløre hjerteinfarkt (vg.no 18.11.2015).)

(Anm: Speilet som ser et fremtidig hjerteinfarkt. (…) Det smarte speilet «Wize mirror» ser ut som et vanlig speil, men inneholder 3D-skannere, multispektrale kameraer og gass-sensorer for å vurdere helsen til den står foran det. Speilet gjør dette gjennom å undersøke personens ansikt, vurdere fettvev, blodgjennomstrømning, ansiktsuttrykk og ansiktsfarge. (gemini.no 18.11.2015).)

(Anm: How Smoking Wrecks Your Looks. See how lighting up can add years to your appearance, causing sagging skin, hair loss, and more. (webmd.com 19.11.2015).)

(Anm: What Does Your Face Say About Your Health? (webmd.com 20.3.2017).)

(Anm: Common antidepressant may change brain. (…) A commonly prescribed antidepressant may alter brain structures in depressed and non-depressed individuals in very different ways, according to new research at Wake Forest Baptist Medical Center. (...) MRI images taken at the end of the treatment phase revealed that in depressed subjects the drug significantly increased the volume of one region of the brain, the anterior cingulate cortex, while decreasing the volume of this same region and the hippocampus in non-depressed subjects. Both of these areas are highly interconnected with other areas of the brain; are critical in a wide array of functions including memory, learning, spatial navigation, will, motivation and emotion; and are implicated in major depressive disorder. (medicalnewstoday.com 7.9.2015).)

(Anm: Antipsychotic drugs linked to brain tissue loss in patients with schizophrenia. Antipsychotic medications are the most common treatment for individuals with schizophrenia, helping to relieve some of the debilitating symptoms caused by the disorder. But according to a new study, long-term use of these drugs may also negatively impact brain structure. Researchers say long-term use of antipsychotic medications - particularly first-generation antipsychotics - may lead to gray matter loss in the brain. First author Dr. Antonio Vita, professor of psychiatry at the University of Brescia in Italy, and colleagues publish their findings in the journal Biological Psychiatry. (medicalnewstoday.com 7.9.2015).)

(Anm: Gray Matter Abnormalities in the Inhibitory Circuitry of Young Binge Drinkers: A Voxel-Based Morphometry Study. (…) Binge drinking (BD) is defined as a pattern of high alcohol intake in a short time followed by periods of abstinence. Front. Psychol., 13 September 2017.)

(Anm: Antipsykotika kan krympe hjernevolumet (Antipsychotics May Shrink Brain Volume) (medpagetoday.com 8.2.2011).)

(Anm: Gray matter abnormality predicts neurodevelopmental problems in smaller premature babies (medicalnewstoday.com 8.4.2016).)

(Anm: Bruk av antipsykotika blandt fosterhjemsungdom med diagnostisert ADHD øker (Antipsychotic drug use among ADHD-diagnosed foster care youth is increasing) (...) Antipsykotika forskrives ofte utenfor indikasjon, slik som behandling av barn og unge med oppmerksomhetssvikt-hyperaktivitets-syndrom (ADHD). Resultatene fra en studie på bruk av "atypiske antipsykotika" blant ungdom med ADHD, sammenlignet aldersgrupper, valgbarhet innen Medicaid, og bruk innen fosteromsorg er presentert i det fagfellevurderte medisinske tidsskriftet Journal of Child and Adolescent Psychopharmacology, fra utgiverne Mary Ann Liebert, Inc. (medicalnewstoday.com 9.4.2014).)

- Forskrivning utenfor preparatomtale høyest for psykofarmaka

Off-label Atypical Antipsychotics (Forskrivning utenfor preparatomtale av atypiske antipsykotika)
JAMA. 2012;308(12):1198 (September 26, 2012)
Det er begrenset dokumentasjon som støtter forskrivning av atypiske antipsykotika utenfor preparatomtale, ifølge en gjennomgang av bevisene hos Agency for Healthcare Research and Quality (AHRQ). (There is limited evidence to support most off-label use of atypical antipsychotics, according to a review of the evidence by the Agency for Healthcare Research and Quality (AHRQ).)

Increasing off-label use of atypical antipsychotics and requests for information about such use led the AHRQ to review the data to date (http://tinyurl.com/9am42ag). Medications of this class of drugs are approved by the US Food and Drug Administration for the treatment of schizophrenia and bipolar disorder, and a few have also been approved for major depression and autism-related aggression. Yet they are often prescribed for other indications.

There is a small but growing evidence base for the use of certain atypical antipsychotic medications in the treatment of obsessive-compulsive disorder, combat-related posttraumatic stress disorder, and generalized anxiety disorder. The review found insufficient evidence to assess the use of such drugs for borderline personality disorder or Tourette syndrome in adults. Evidence did, however, suggest that atypical antipsychotics do not increase body weight in patients with anorexia, despite the association of these drugs with weight gain in other patients. (...)

(Anm: Legemiddelforskrivning (feilforskrivning, overmedisinering, deforskrivning (seponering) (mintankesmie.no).)

(Anm: Importance of Early Weight Changes to Predict Long-Term Weight Gain During Psychotropic Drug Treatment. Background: Psychotropic drugs can induce substantial weight gain, particularly during the first 6 months of treatment. (…) Results: Prevalences of metabolic syndrome and obesity were 22% and 17%, respectively, at baseline and 32% and 24% after 1 year. (…) Conclusion: Following prescription of weight gain–inducing psychotropic drugs, a 5% threshold for weight gain after 1 month should raise clinician concerns about weight-controlling strategies. (J Clin Psychiatry 2015;76(11):e1417–e1423).)

(Anm: Metabolic Syndrome Components Are Associated With Symptomatic Polyneuropathy Independent of Glycemic Status. Diabetes Care 2016 (March 10, 2016).)

(Anm: New cause of immune neuropathy discovered. Hope for a better diagnosis. "Our study backs the assumption from previous studies that patients who have antibodies against proteins of Nodes of Ranvier exhibit characteristic features," says Kathrin Doppler. This means: The disease develops rapidly, causes severe paralysis and responds poorly to standard therapy with corticosteroids or immunoglobulins but excellently to Rituximab treatment. The Würzburg neurologists found that strong neuralgia is another typical symptom in patients with Caspr antibodies. Patients with antibodies against the two other proteins, Neurofascin-155 and Contactin-1, in contrast typically exhibit a distinct tremor in targeted movements. (medicalnewstoday.com 9.8.2016).)

(Anm: Auto-antibodies to contactin-associated protein 1 (Caspr) in two patients with painful inflammatory neuropathy. Brain. 2016 Jul 29. pii: aww189. [Epub ahead of print].)

(Anm: Prepsychosis links with elevated metabolic syndrome. MADRID – Untreated people at high risk for developing psychosis also showed an increased prevalence of certain components of metabolic syndrome in data collected from 163 German study participants, a finding that gives new insight into the well-documented but poorly delineated link between schizophrenia and metabolic syndrome. (...) He also suggested prescribing antipsychotic medications that pose the lowest risk for causing further metabolic derangements in patients. (clinicalpsychiatrynews.com.com 2.4.2016).)

(Anm: Joachim Raese, MD. Metabolic syndrome is defined by the aggregation of hypertriglyceridemia, low high-density lipoprotein (HDL) levels, elevated fasting glucose, hypertension, and increased waist circumference. Metabolic syndrome confers an increased risk of developing diabetes and of dying from coronary artery disease. Cardiovascular disease is the leading cause of death among patients with schizophrenia, who have a life expectancy about 20 years shorter than the general population. (…) For a more detailed discussion, I suggest watching a YouTube video that we have prepared. (cmeinstitute.com 27.4.2016).)

(Anm: Video Lecture 8: Metabolic Syndrome Lectures 1 (By Dr. Joachim Raese) (youtube.com).)

(Anm: Women with type 2 diabetes at greater cardiovascular risk than men. While it is well established that individuals with diabetes are at higher risk for cardiovascular disease, a new scientific statement from the American Heart Association claims this risk may be significantly greater for women with the condition. Published in the journal Circulation, the statement also says women with type 2 diabetes may need to take more action than men to lower their risk for heart attack and stroke. (medicalnewstoday.com 8.12.2015).)

(Anm: Type 2 diabetes: blood pressure drugs may be harmful for some patients. For some patients with type 2 diabetes, treatment with intense blood-lowering medication may do more harm than good. This is according to a new study published in The BMJ. (medicalnewstoday.com 26.2.2016).)

(Anm: Sex Differences in the Cardiovascular Consequences of Diabetes Mellitus: A Scientific Statement From the American Heart Association. Circulation. 2015; 132(25): 2424-47.)

- Styrelse skærper overvågning off label-brug af medicin

Styrelse skærper overvågning off label-brug af medicin
dagenspharma.dk 2.2.2015
Et nyt IT-system i 2012 har rustet Sundhedsstyrelsen til at afsløre en stribe tilfælde af farlig off label-brug af medicin. Systemet gør det for første gang muligt at regulere brugen og øge sikkerheden ved brug af lægemidler uden for indikation.

Lovgivningen om øget lægemiddelovervågning af off label-brug, som blev indført i 2012, har givet pote. Det konkluderer Sundhedsstyrelsen i en ny rapport ’overvågning af sikkerheden ved off label-brug af medicin i Danmark’. Af rapporten fremgår det, at Sundhedsstyrelsen især har kunnet afsløre hidtil ukendt off label-brug ved hjælp af ’signalgenereringsværktøjet’ – et nyt it-system, som […]

- Tusindvis af børn får medicin, der kun er godkendt til voksne

Tusindvis af børn får medicin, der kun er godkendt til voksne
frdb.dk 17.3.2015
Medicin - I 2013 blev der udskrevet lægemidler til over 600.000 børn og unge. Nogle midler, som vacciner, er testet og godkendt til børn, mens mange typer allergimedicin, p-piller og hudlægemidler udskrives off-label.

Medicin bruges off-label, når en læge bruger medicin til et formål, det ikke er godkendt til. Flere studier har vist, at off-label-brug af medicin til børn er meget udbredt, fordi medicin sjældent testes til børn.

- Helt konkret betyder det, at helt små børn på grund af en ’umoden’ lever- og nyrefunktion skal have mindre doser, end deres størrelse indikerer. Omvendt har lidt større børn en fantastisk kapacitet til at omsætte lægemidler, så der vil være en risiko for at underdosere, siger Helle Holst til metroxpress.

En dansk forskningsartikel fra 2011 viste, at en femtedel af alle bivirkninger rapporteret i børn over en tiårs periode var associeret med brug af medicin off-label, og 60 procent af bivirkningerne var alvorlige. (…)

- Åpenhet om kliniske forsøk – Motgift mot svakere off-label promotering?

Clinical Trial Transparency — Antidote to Weaker Off-Label-Promotion Rules? (Åpenhet om kliniske forsøk – Motgift mot svakere off-label promotering?)
N Engl J Med 2014; 371:1-3 (July 3, 2014)
Dette året synes å være en gunstig periode for de jevnlige slag om formidlingen av biomedisinsk forskning. Enkelte firmaer som ber om større frihet til å markedsføre sine produkter har gått ut mot de nylige retningslinjer fra den amerikanske legemiddelkontrollen Food and Drug Administration (FDA) om markedsføring av legemidler og utstyr for off-label-bruk, og hevder at de krenker First Amendment. Samtidig er industrien delt i kravet om økt åpenhet om kliniske resultater. Men idet FDAs reguleringsmyndighet er svekket av utfordringer mht. First Amendment er behovet for åpenhet om kliniske forsøk mer presserende. (…) (This year promises to be an auspicious period for some long-running battles over the dissemination of biomedical research. Some companies seeking more freedom to promote their products have bristled at recent guidance documents from the Food and Drug Administration (FDA) regarding promotion of drugs and devices for off-label uses, claiming that they violate the First Amendment. Simultaneously, industry is divided over calls for increased transparency of clinical trial results. But as the FDA's regulatory authority is weakened by First Amendment challenges, the need for clinical trial transparency becomes more urgent.)

(Anm: Fri tilgang til forskningsresultater? (forskningsdata) (mintankesmie.no).)

(Anm: The hidden side of clinical trials | Sile Lane | TEDxMadrid (youtube.com).)

(Anm: Forvaltningsmakt og kunnskapspolitikk. Sammendrag. Helse- og omsorgsdepartementet benekter at de ønsker å styre forskninga i underliggende etater, og ser ingen problemer med at forskninga ligger under forvaltninga. Rus & Samfunn 05 / 2016 (Volum 9) Side: 33-35.)

(Anm: Frie forskere eller maktens lakeier? Abstrakt. Det går et skisma gjennom den samfunnsvitenskapelige rusforskningen. Ved første øyekast er det vanskelig å forstå hvorfor. Rus & Samfunn 05 / 2016 (Volum 9) Side: 36-40.)

(Anm: Nesten halvparten av alle studier som er gjennomført av store sponsorer i det siste tiåret er upublisert (Nearly half of all trials run by major sponsors in past decade are unpublished.) BMJ 2016;355:i5955 (Published 04 November 2016).)

(Anm: Who's not sharing their trial results? (trialstracker.ebmdatalab.net).)

(Anm: Transparency for patients: How much is too much? (pharmafile.com 11.10.2016).)

(Anm: Parlamentsmedlemmer hører at kliniske forsøk er byråkratiske, uklare, og forvirrende for forskere og pasienter. (…) "Det har vært en rekke kjente tilfeller hvor godkjente legemidler er basert på ufullstendig informasjon — og hvor den informasjonen som senere er stilt til rådighet har vist at legemidlet er ineffektivt eller faktisk skadelig.  (Clinical trials are bureaucratic, opaque, and offputting to researchers and patients, MPs hear.) BMJ 2013;346:f1711 (14 March 2013).)

(Anm: Court rules that FDA cannot restrict off-label marketing. BMJ 2015;351:h4367. (Published 11 August 2015).)

(Anm: Amarin og FDA udskyder afgørelse om "off label" igjen. Irske Amarin og FDA har endnu engang bedt retten om udskydelse i en sag om Amarins ”off label” brug af selskabets fiskeoliepille. (…) Kvalitetsjournalistik kræver investeringer. Ifølge mediet har de to parter indikeret, at de er tæt på at nå et forlig i en sag, der handler om Amarins rettigheder til at promovere såkaldt off label-brug af Vascepa, der betyder i indikationer, hvor den ikke er blevet godkendt af myndighederne. Alligevel har man nu for tredje gang bedt en domstol i New York om en mindre udsættelse. Denne gang har parterne bedt om udsættelse indtil 18. marts. (medwatch.dk 22.2.2016).)

- Vi ønsker ikke off label-bruk, sier overlege Steinar Madsen i Legemiddelverket

Høyt spill med pasienter
farmatid.no 22.11.2010 (Publisert i NFT nr. 11/2010, side10-16)
Bruken av legemidler utenfor godkjent indikasjon i Norge er omfattende, uoversiktlig og full av dilemma. — Vi ønsker ikke off label-bruk, sier overlege Steinar Madsen i Legemiddelverket.

I finanskrisetider og med en stadig aldrende befolkning ser også helsemyndigheter etter måter å spare penger på. Blant annet ved å gi pasienter legemidler utenfor godkjent indikasjon. Norske leger og helseforetak er villige til å ta sjanser på pasienters vegne, og det for en budsjettpost, legemidler, som kun utgjør vel ti prosent av det totale helsebudsjettet. Bruken av såkalte off label- og off licence-legemidler i Norge har pågått i årevis og i betydelig omfang, ifølge leger Norsk Farmaceutisk Tidsskrift har snakket med. Pasientrisikoen er høy. Rapportering skjer unntaksvis. Praksisen er løs, uoversiktlig og full av dilemma. (...)

(Anm: Gro R. Wesenberg, direktør, Statens legemiddelverk og Hans Petter Aarseth, divisjonsdirektør, Helsedirektoratet. Leserbrev: Off label-bruk av legemidler (farmatid.no 24.1.2011).)

(Anm: Pasientsikkerhet (rettssikkerhet) (mintankesmie.no).)

(Anm: Court rules that FDA cannot restrict off-label marketing. BMJ 2015;351:h4367. (Published 11 August 2015).)

(Anm: Dom kan stække FDA. En amerikansk domstol har afgjort, at myndighederne ikke har ret til at blande sig i, hvordan medicinalfirmaet Amarin markedsfører dets fiskeolie. Domsafgørelsen kan være med til at indskrænke FDA’s råderum. (dagenspharma.dk 10.8.2015).)

- Ansvar og oppfølging ved bruk av legemidler utenfor godkjent indikasjon

Å tøyle et problembarn
farmatid.no 22.11.2010
Legemidler som benyttes utenfor godkjent indikasjon skaper hodebry. På den ene siden kan bruken av såkalt off label-medisin være grensesprengende i oppdagelsen av nye bruksområder, på den annen side det rene lotteri med fatal utgang. At økonomi spiller en sentral rolle, er en ytterligere kompliserende faktor. Det er ikke til å undres over at mange har et elsk/hat-forhold til problembarnet.

Off label-forskrivning er lovlig, men det forutsetter et spesielt ansvar med tanke på innsikt, forsvarlighet og informasjonsplikt. Legen skal med andre ord være svært bevisst i sitt valg av ikke-godkjente legemidler. Vanskeligheter oppstår idet denne forskrivningspraksisen blir en sovepute, det vil si at alternativer aldri vurderes. Da bør varselklokkene kime.

For off label-bruk er et vågespill, det er udiskutabelt. Den store haken er mangelfull dokumentasjon. Mest alvorlig er likevel pasientrisikoen. Å benytte ikke-godkjente legemidler kan neppe ses på som annet enn gambling med pasienter. (...)

- Hvordan kan eller bør den norske helsetjenesten håndtere off-label bruk av legemidler?

Ansvar og oppfølging ved bruk av legemidler utenfor godkjent indikasjon
kvalitetogprioritering.no 11.4.2011 (Nasjonalt råd for kvalitet og prioritering i helsetjenesten)
Bruk av legemidler utenfor godkjent indikasjon, ”off-label” bruk, omfatter forskrivning av registrerte legemidler utenfor godkjent bruksområde. Nasjonalt råd for kvalitet og prioritering i helsetjenesten har tidligere behandlet en sak som berører denne problemstillingen: ”Innføring av ny og kostbar teknologi - Lucentis vs. Avastin”. Hvordan kan eller bør den norske helsetjenesten håndtere off-label bruk av legemidler? (...)

I diskusjonen som fulgte ble det understreket at foretakene fortsatt har behov for en avklaring i forhold til sitt ansvar ved bruk av legemidler utenfor godkjent indikasjon. I forlengelsen av dette ble det også opplyst at Helsedirektoratet nå har besvart henvendelsen fra LMI, som rådet videresendte til Helsedirektoratet i februar 2010. Svarbrevet fra Helsedirektoratet er stilet til Helsetilsynet i Sør-Trøndelag. Årsaken til det var at Helsedirektoratet hadde mottatt flere henvendelser om dette temaet på samme tid, og hadde valgt å svare Helsetilsynet i fylket med kopi til øvrige som hadde henvendt seg. Nasjonalt råd var uteglemt. (...)

- FDAs tilsyn med legemiddelfirmaers reklame for bruk utenfor preparaomtale er dårlig, ifølge "vaktbikkje"

Læger bruger Novo-medicin uden godkendelse
business.dk 24.6.2011
Selv om Novoseven er blødermedicin og kun godkendt til dette formål, bruges præparatet også i Danmark til at standse blødninger hos ikke-blødere – f.eks. patienter med voldsomme skader efter en trafikulykke.

Læger fortsætter med at bruge blødermedicinen Novoseven til ikke godkendte formål – selv om Novo Nordisk forlængst har opgivet at dokumentere effekten, og på trods af at uafhængige undersøgelser tyder på alvorlige bivirkninger. Det skæppede sidste år 1,2 milliarder kr. i Novo Nordisks kasse.

Læger verden over tyr fortsat til Novo Nordisks blødermedicin Novoseven som sidste udvej, når de står med traumepatienter med alvorlige blødninger eller kvinder, der er ved at forbløde efter en fødsel. Sidste år hentede Novo Nordisk omkring 1,2 milliarder kr. hjem på salg af Novoseven til ikke godkendte formål, mens beløbet i 2008 var omkring én milliard kr.

Det sker selv om den amerikanske Food and Drug Administration (FDA, der administrerer USAs lovgivning om fødevarer og lægemidler, red.) i 2006 advarede mod bivirkningerne ved at bruge Novoseven til ikke godkendte formål, og selv om Novo Nordisk i 2008 standsede alle forsøg med Novoseven til traumebehandling. (...)

(Anm: Former Pfizer employee loses another bid to press illegal marketing lawsuit. A federal appeals court last week refused to revive a lawsuit in which a former Pfizer employee alleged the company promoted off-label use of its Lipitor cholesterol pill. In doing so, however, the court also raised a question about the extent to which drug makers may be held responsible for causing federal health programs, such as Medicare and Medicaid, to overpay for a medicine. (statnews.com 24.5.2016).)

Widespread off-label drug prescription raises safety concerns (Utstrakt forskrivning utenfor preparatomtale gir grunnlag for sikkerhetsbekymringer)
ottawacitizen.com 1.1.2009
(...) Dudley had no idea that the drug she was taking for nerve pain, gabapentin, had been approved in Canada only for epilepsy, and not for pain. Nor could she know that six years later - this past month - the U.S. Food and Drug Administration would announce it will require the makers of gabapentin and other anti-epileptics to warn that their use increases the risk of suicidal thoughts and behaviour.

The drugs are among the most heavily prescribed for "off-label" uses, meaning for conditions for which they have never been approved.

Thousands of times a day in Canada, patients are prescribed drugs off-label. The practice is burgeoning, it is legal and most of it occurs with little to no scientific backing.

Of the 423 million prescriptions filled by drugstores across Canada last year, an estimated one quarter - 89 million prescriptions - were written off-label. (...)

FDA oversight of drug company promotion of off-label use is poor, US watchdog says (FDAs tilsyn med legemiddelfirmaers reklame for bruk utenfor preparaomtale er dårlig, ifølge "vaktbikkje".)
BMJ 2008;337:a1163 (5 August)
The US Food and Drug Administration does a poor job of monitoring drug companies’ promotion of unapproved or "off-label" uses of their drugs, says a report by the US Government Accountability Office, the investigative arm of Congress.

Charles Grassley, an Iowa senator who is the senior Republican member of the Senate Committee on Finance, asked the accountability office to review the FDA’s effectiveness in monitoring drug companies’ efforts to promote off-label uses. He said he was concerned about the possible effects of such promotion on doctors’ prescribing practices and on patients’ safety.

Although doctors may prescribe drugs off label for indications that have not been approved by the FDA, drug companies are forbidden from promoting such unapproved uses. (...)

FDA Poorly Equipped To Enforce Off-Label Prescription Drug Marketing Rules, GAO Report Finds
kaisernetwork.org 28.7.2008
FDA takes an average of seven months to issue warnings to pharmaceutical companies that market medications for off-label uses, and those companies take an average of four months to address the violations, according to a draft report compiled by the Government Accountability Office, the AP/Minneapolis Star Tribune reports. The report found that FDA has no employees specifically assigned to monitor whether pharmaceutical companies market medications for off-label uses. (...)

Report: Drug companies that promote unapproved uses face little risk of getting caught
startribune.com 27.7.2008
WASHINGTON - When a state trooper pulls over a speeding motorist, the officer usually writes out a ticket on the spot.

When federal regulators catch a drug company peddling prescription medications for an unapproved use, it takes them an average of seven months to issue a warning, according to a draft report by congressional investigators. It typically takes four more months for the company to fix the problem. During that time, a lot prescriptions can be written.

The report from the Government Accountability Office delves into a gray area of medical practice and federal oversight: the use of medications to treat conditions other than the ones the drugs were approved for, a practice known as "off-label" prescribing. (...)

FDA Guidance on Off-Label Promotion and the State of the Literature From Sponsors
JAMA 2008;299(16):1949-1951
Although the US Food and Drug Administration (FDA) reviews and approves drugs for specific indications, the approval does not usually limit the use of those drugs in clinical practice. Indeed, prescribing for indications not reviewed by the FDA ("off-label") is common. In a recent study of 160 frequently prescribed drugs,1 off-label use represented 21% of drug mentions, and 73% of these off-label uses had little or no scientific support. Off-label use has long been controversial because large numbers of patients may receive drugs that have had only limited testing for efficacy and safety, and some off-label uses may eventually be shown to have an unfavorable risk-benefit profile. High-profile examples include the use of the combination of fenfluramine and phentermine by millions of persons for weight loss and the widespread use of hormone therapy by postmenopausal women to prevent coronary artery disease. (...)

Drug Company Coalition To Push for Looser Rules on Off-Label Marketing
kaisernetwork.org 18.4.2008
Representatives of pharmaceutical companies are expressing support for loosening rules regarding drug companies' ability to market medications for off-label uses, the Wall Street Journal reports (Mundy, Wall Street Journal, 4/18). According to the Journal, the drug industry has recently become concerned over a "potential regulatory backlash" stemming from recent issues with the marketing of Vioxx and Vytorin, growing criticism from the presidential candidates regarding drug pricing and ongoing investigations by three congressional committees into drug-industry marketing practices. (...)

Critics Say FDA’s Off-Label Guidance Allows Marketing Disguised as Science (Kritikere sier at FDAs veiledning for forskrivning utenfor preparatomtale tillater markedsføring forkledt som vitenskap)
JAMA. 2008;299(15):1759-1761
Proposed guidelines by the US Food and Drug Administration (FDA) addressing drug and device manufacturers' dissemination of journal article reprints that discuss off-label use of these products have come under fire.

Critics say the proposed guidance, as currently written, will allow companies to selectively use as a marketing tool peer-reviewed journal articles that support off-label use of their products. They also argue the guidelines could possibly harm public health by allowing manufacturers a back door for putting products into the health care setting for unapproved uses without having to conduct rigorous clinical studies to gain FDA approval.

The draft guidance, Good Reprint Practices, was issued February 15 with the FDA accepting comments through April 21 (http://www.fda.gov/oc/op/goodreprint.html). The FDA said the draft guidance represents its current thinking on the topic and may be modified based on the comments it receives. (...)

When there's little proof a prescription drug will work (Når der er lite bevis for at legemiddelforskrivning vil virke)
latimes.com 15.5.2006
Legemidler utenfor preparatomtale er blitt mer populært selv om de ofte mangler vitenskapelig støtte, viser en ny studie. ('Off-label' medicines are becoming more popular even though they often lack scientific support, a new study shows.)

Millioner av amerikanere blir hvert år forskrevet legemidler, som ikke er godkjent for deres spesielle medisinske tilstand, en praksis som er lovlig og logisk i mange tilfeller. Men en ny studie har vist at drøyt 20 % av alle forskrivninger er anordnet for slik ikke-godkjent bruk og at de fleste av disse — trekvart — er ikke godt undebygget av vitenskapelige studier. (Millions of Americans each year are prescribed drugs that are not approved for their specific medical condition, a practice that is legal and logical in many cases. But a new study has found that fully 20% of all prescriptions are written for such nonapproved uses and that most of these — three-quarters — are not well-supported by scientific studies.)

Den utstrakte bruk av legemidler "utenfor preparatomtale" kan true pasientens sikkerhet samtidig som den unngår oppmerksomhet fra statlige kontrollorganer, antyder noen eksperter. (...) (This widespread use of medications "off-label" could threaten patients' safety while escaping the attention of federal regulators, some experts suggest.)

Studien, publisert sist uke i Archives of Internal Medicine, ble 3 500 tilfeldig utvalgte leger utspurt om alle sine pasientbehandlinger i løpet av to dager i strekk i 2001, og alle de legemidler de måtte ha forskrevet. Forskerne innhentet informasjon på de 100 mest vanlig forskrevne legemidler så vel som ytterligere 60 tilfeldig utvalgte legemidler. (...) (The study, published last week in the Archives of Internal Medicine, polled 3,500 randomly selected doctors on all of their patient interactions over two consecutive days in 2001, including any drugs they may have prescribed. Researchers then retrieved information on the 100 most commonly prescribed drugs as well as 60 more drugs that were randomly selected.)

Blant andre ting fant forskerne at hjertemedisiner, antikonvulsiva og astmalegemidler var mest sannsynlig forskrevet utenfor preparatomtale. Psykiatriske legemidler og allergilegemidler var de mest sannsynlige typer legemidler brukt utenfor preparatomtale med liten vitenskapelig støtte. I virkeligheten manglet vitenskapelig støtte for 96 % av de psykiatriske legemidler forskrevet utenfor preparatomtale. (Among other things, the scientists found that cardiac medications, anticonvulsants and asthma medications were the most likely to be prescribed off-label. Psychiatric drugs and allergy medications were the most likely types of drugs to be used off-label with little scientific support. In fact, scientific support was lacking for 96% of the psychiatric drugs prescribed off-label.)

Dr. Randall S. Stafford, førsteforfatter av studien og assosiert professor i medisin ved Stanford Prevention Research Center, sa at resultatene er bekymrende. Selv om legemidler er grundig gjennomgått av Food and Drug Administration før de tillates på markedet, "står ikke FDA inne for sikkerheten for alle de forskjellige måter som legemidler er brukt," sa han. (...) (Dr. Randall S. Stafford, lead author of the study and an associate professor of medicine at the Stanford Prevention Research Center, said the findings were troubling. Even though drugs are thoroughly reviewed by the Food and Drug Administration before they're allowed to go to market, "the FDA does not vouch for the safety and efficacy of all the various ways that drugs are used," he says.)

(Anm: Off-label Prescribing Among Office-Based Physicians. Arch Intern Med. 2006;166:1021-1026.)

Off-label antidepressant use in children and adolescents compared with young adults: extent and level of evidence
Pharmacoepidemiol Drug Saf. 2012 Jul 4. doi: 10.1002/pds.3312. [Epub ahead of print]
PURPOSE: To estimate the degree of, and level of evidence supporting, off-label antidepressant (AD) prescribing for children and adolescents compared with young adults. (...)

RESULTS: Over the study period, 290 816 subjects met eligibility criteria: 17% 5-12 years old, 40% 13-18 years old, and 43% 19-24 years old. Sertraline was the most commonly prescribed index AD (19-23%). Psychiatrists more often prescribed the AD for children (31%) and adolescents (35%) versus young adults (17%). Only 28% of all subjects had a diagnosis consistent with an FDA-approved indication within 30 days pre-index and post-index AD. Children less than 13 years old were less likely to have had an FDA-approved indication (5-10%). Most off-label prescribing had inconclusive to no evidence supporting efficacy. The lack of evidence was especially pronounced for younger children. Trends were consistent over the study period. Increasing the time period for potential indications pre-index and post-index AD did not result in significantly reduced off-label rates.

CONCLUSIONS: Pediatric off-label AD prescribing occurs frequently without a strong evidence base, highlighting a need to generate additional evidence to ensure safe and effective use. (...)

Drug, Patient, and Physician Characteristics Associated With Off-label Prescribing in Primary Care (Legemidler, pasienter og kjennetegn knyttet til forskrivning utenfor preparatomtale i primærhelsetjenesten)
Arch Intern Med. 2012 (Published online April 16)
Bakgrunn Off-label-forskrivning kan føre til uheldige legemiddelhendelser. Lite er kjent om omfanget og utfordringene mht. dokumentasjon av behandlingsindikasjon. (Background Off-label prescribing may lead to adverse drug events. Little is known about its prevalence and determinants resulting from challenges in documenting treatment indication.)

Methods We used the Medical Office of the XXI Century electronic health record network in Quebec, Canada, where documentation of treatment indication is mandatory. One hundred thirteen primary care physicians wrote 253 347 electronic prescriptions for 50 823 patients from January 2005 through December 2009. Each drug indication was classified as on-label or off-label according to the Health Canada drug database. We identified off-label uses lacking strong scientific evidence. Alternating logistic regression was used to estimate the association between off-label use and drug, patient, and physician characteristics.

Results The prevalence of off-label use was 11.0%; of the off-label prescriptions, 79.0% lacked strong scientific evidence. Off-label use was highest for central nervous system drugs (26.3%), including anticonvulsants (66.6%), antipsychotics (43.8%), and antidepressants (33.4%). Drugs with 3 or 4 approved indications were associated with less off-label use compared with drugs with 1 or 2 approved indications (6.7% vs 15.7%; adjusted odds ratio [AOR], 0.44; 95% CI, 0.41-0.48). Drugs approved after 1995 were prescribed off-label less often than were drugs approved before 1981 (8.0% vs 17.0%; AOR, 0.46; 95% CI, 0.42-0.50). Patients with a Charlson Comorbidity Index of 1 or higher had lower off-label use than did patients with an index of 0 (9.6% vs 11.7%; AOR, 0.94; 95% CI, 0.91-0.97). Physicians with evidence-based orientation were less likely to prescribe off-label (AOR, 0.93; 95% CI, 0.88-0.99), a 7% reduction per 5 points in the evidence section of the Evidence-Practicality-Conformity Scale.

Conclusions Off-label prescribing is common and varies by drug, patient, and physician characteristics. Electronic prescribing should document treatment indication to monitor off-label use. (...)

What Does Off-label Prescribing Really Mean?
Arch Intern Med. 2012 (Published online April 16)
The issue of off-label prescribing is a loaded subject. When one scratches the surface, one realizes the myriad limitations of such a construct related to the process of labeling, the monitoring of appropriate prescribing, the inadequacy of evidence to match the complexities of care, and the missed opportunities of leveraging our information systems to better optimize medication use for the care of patients. (...)

Off-Label Sales of SSRIs Leads To More Litigation (Salg av SSRI-preparater utenfor preparatomtale fører til flere søksmål)
by Evelyn Pringle
opednews.com 22.2.2007
Off-label prescribing of prescription drugs overall is widespread in the US, but nowhere is it more prevalent than with the antidepressant drugs known as selective serotonin reuptake inhibitors. A study in the June 2005, Journal of Clinical Psychiatry, found that 75% of the prescriptions written for SSRIs were for treatments not approved by the FDA.

The study's lead author, Dr Hua Chen, an assistant professor at the University of Houston, said the findings reveal a significant gap in the US drug safety system and off-label prescribing regularly exposes consumers to drugs that are untested for their condition. (...)

(Anm: Off-label use of antidepressant, anticonvulsant and antipsychotic medications among Georgia medicaid enrollees in 2001. J Clin Psychiatry. 2006 Jun;67(6):972-82.)

- Forskriver antidepressiva uten diagnose

Forskriver antidepressiva uten diagnose
dagensmedisin.no 12.1.2012
Leger på sykehjem forskriver antidepressiva uten utredning og diagnose, og de stoler på sykepleiernes observasjoner.

Antidepressiva er vanligvis den eneste behandlingen som tilbys beboere ved sykehjem, og legene utreder og diagnostiserer sjelden for depresjon.

Dette fremgår av en norsk kvalitativ studie som nylig er publisert. (...)

(Anm: Treatment decisions on antidepressants in nursing homes: a qualitative study. Scand J Prim Health Care. 2011 Dec;29(4):252-6.)

- Pfizer versus Kaiser: forsikringsselskp vil ha sin dag i retten

Off-label Marketing
Pfizer versus Kaiser: insurers want their day in court (Pfizer versus Kaiser: forsikringsselskp vil ha sin dag i retten)
BMJ 2013;346:f3738 (12 June 2013)
Legemiddelfirmaer har betalt ut milliarder i bøter for ulovlig markedsføring, men en fersk rettslig kjennelse kan nå også oppmuntre forsikringsselskaper til å søke kompensasjon, Ed Silverman undersøker (Drug companies have paid out billions in fines for illegal marketing, but a recent court ruling may now give insurance firms encouragement to seek their pound of flesh as well, Ed Silverman investigates)

In a move that is certain to put the pharmaceutical industry on the defensive, a federal appeals court panel recently issued a pair of rulings against Pfizer that could encourage insurers and health plans to file a surge of lawsuits—if they can prove they paid unnecessarily for illegally marketed medicines.

In the first instance, the US First Circuit Court of Appeals upheld a lower court ruling that the world’s largest drug maker should pay $142m (£91m; €107m) to the Kaiser Foundation Health Plan, which claimed damages for covering the epilepsy drug gabapentin (Neurontin) for off-label uses, including bipolar disorder, migraines, and neuropathic pain.

In the other ruling, the appeals court overturned a different lower court ruling and allowed Aetna, one of the largest US insurers, and a health plan run by Harden Manufacturing to revive their lawsuits, which claimed that Pfizer engaged in racketeering and induced physicians to prescribe gabapentin for the same unapproved uses. (...)

- Abbott Laboratories betaler 1,6 milliarder dollar for å promotere valproate (Depakote) utenfor preparatomtale

Abbott pays $1.6bn for promoting off label use of valproic acid (Abbott Laboratories betaler 1,6 milliarder dollar for å promotere valproate (Depakote) utenfor preparatomtale)
BMJ 2012;344:e3343 (11 May)
The drug company Abbott Laboratories has agreed to pay $1.6bn (£0.9bn; €1.2bn) in penalties for improper promotion of the drug Depakote (valproic acid) in the US. The settlement is the second largest by a drug manufacturer and ends a four year investigation by federal and state officials.

The company acknowledged training a workforce to promote off label use of the drug to nursing homes to control agitation and aggression in older schizophrenia patients and in patients with dementia. The judgment says that Abbott also made illegal payments to doctors and pharmacists to encourage them to promote or prescribe valproic acid outside its licensed indications.

“Not only did Abbott engage in off label promotion, but it targeted elderly dementia patients and downplayed the risks apparent from its own clinical trials,” said Tony West, acting associate Attorney General at a news conference in Washington, DC on 7 May.

Abbott closed a trial of Depakote in patients with dementia in 1999 because of increased incidents of adverse events. (...)

(Anm: Former Pfizer employee loses another bid to press illegal marketing lawsuit. A federal appeals court last week refused to revive a lawsuit in which a former Pfizer employee alleged the company promoted off-label use of its Lipitor cholesterol pill. In doing so, however, the court also raised a question about the extent to which drug makers may be held responsible for causing federal health programs, such as Medicare and Medicaid, to overpay for a medicine. (statnews.com 24.5.2016).)

Abbott Laboratories agrees to $1.6 billion settlement over marketing of Depakote
washingtonpost.com 8.5.2012
Global pharmaceutical giant Abbott Laboratories has agreed to pay federal and state governments $1.6 billion in criminal and civil fines for illegally promoting unapproved uses of its drug Depakote, including to sedate elderly patients in nursing homes, officials announced Monday.

The settlement, which includes an agreement to plead guilty to a criminal misdemeanor, is the second-largest in a string of multimillion-dollar payouts in recent years resulting from stepped-up enforcement by the Justice Department and state investigators against drugmakers that “misbrand” their products. (...)

(Anm: Depakote (Valproate, Orfiril etc.) (dailymed.nlm.nih.gov).)

US judge fines Johnson & Johnson $1.1bn for misleading marketing of risperidone (Amerikansk dommer ilegger Johnson & Johnson 1,1 milliarder i bot for villedende markedsføring av risperidone)
BMJ 2012;344:e2772 (16 April)
Judge Tim Fox of the Arkansas Circuit Court fined the Johnson & Johnson subsidiary Janssen Pharmaceuticals $1.1bn (£0.7bn; €0.84bn) for promotional information about the antipsychotic drug risperidone that misled the state into spending Medicaid funds for the drug. He also fined the company $11m for violating the state’s law on deceptive practices. Medicaid is a joint federal and state health insurance scheme for people on low incomes. (...)

A jury decided that Johnson & Johnson had defrauded the Medicaid programme. Fox fined the company for 238 000 violations of the state’s Medicaid fraud laws over nearly four years since 2002. He set a fine of $5000 for each violation. (...)

(Anm: Risperdal (risperidone) (mintankesmie.no).)

J.&J. Fined $1.2 Billion in Drug Case
nytimes.com 12.4.2012
A judge in Arkansas ordered Johnson & Johnson and a subsidiary to pay more than $1.2 billion in fines on Wednesday, a day after a jury found that the companies had minimized or concealed the dangers associated with an antipsychotic drug.

Risperdal is approved to treat schizophrenia, bipolar disorder and behavior problems.

The fine, which experts said ranked among the largest on record for a state fraud case involving a drug company, is the most recent in a string of legal losses for Johnson & Johnson related to its marketing of the drug, Risperdal. (...)

(Anm: Risperdal (risperidone) (mintankesmie.no).)

Drug Maker Will Pay Fine for Promoting Off-Label Use
nytimes.com 30.8.2006
The Schering-Plough Corporation agreed on Tuesday to pay $435 million and plead guilty to conspiracy to settle a federal investigation into marketing of its drugs for unapproved uses and overcharging Medicaid for certain drugs.

Schering-Plough said it would pay $255 million to resolve civil aspects of the previously disclosed investigation. A subsidiary, the Schering Sales Corporation, will pay a criminal fine of $180 million and plead guilty to one count of conspiracy to make false statements to the government. The agreement is subject to court approval.

Schering-Plough said the settlement resolved an investigation by the Justice Department and the United States attorney’s office in Boston that began before a new management team took over at the company in April 2003. (...)

Merck betalar miljardbelopp för Vioxx
lakemedelsvarlden.se 23.11.2011
Läkemedelsföretaget Merck har valt att betala 950 miljoner dollar för att man marknadsförde det nu indragna smärtläkemedlet Vioxx som behandling för en icke godkänd indikation. (...)

- Det amerikanske justisdepartementet skriver i sin kunngjøring at GlaxoSmithKline skjulte studier som hadde negative funn

GlaxoSmithKline is fined record $3bn in US (GlaxoSmithKline er ilagt rekordbot på 3 milliarder dollar i USA)
BMJ 2012;345:e4568 (3 July)
GlaxoSmithKline har inngått avtale om å erkjenne skyld og betale 3 milliarder dollar (£ 2 milliarder, € 2,4 mrd) i straff for ulovlig markedsføring av reseptbelagte legemidler, unnlatelse av å rapportere sikkerhetsdata og falsk prisrapportering. (GlaxoSmithKline has agreed to plead guilty and pay $3bn (£2bn; €2.4bn) in penalties for unlawful promotion of prescription drugs, failure to report safety data, and false price reporting.)

Det er også inngått en 123 siders avtale om bedriftens integritet med det amerikanske justisdepartementet som regulerer firmaets aktiviteter de neste fem årene.1 (...) (It also signed a 123 page corporate integrity agreement with the US Department of Justice that regulates its activity for the next five years.1)

GSKs avtale omfatter flere av dets ledende legemidler. De markedsførte ulovlig antidepressivaet Seroxat (paroxetine / fornorsket paroksetin) for behandling av pasienter under 18 år, selv om Food and Drug Administration (legemiddelkontrollen) aldri godkjent legemiddel for denne aldersgruppen. Firmaet har også utarbeidet "villedende" tidsskriftartikler som hevder Seroxat hadde effekt for denne befolkningsgruppen når "studien ikke viste effekt,« Det amerikanske justisdepartementet sa i sin kunngjøring at de skjulte studier som hadde negative funn.3 (GSK’s agreement covers several of the its leading drugs. It illegally promoted the antidepressant paroxetine for treating patients under the age of 18, even though the Food and Drug Administration never approved the drug for that age group. The company also created “misleading” journal articles claiming efficacy of paroxetine in that population, when in fact “the study failed to demonstrate efficacy,” the justice department said in its statement, and it hid trials that had negative findings.3)

GSK markedsførte ulovlig bupropion for vekttap, seksuell dysfunksjon, substansavhengighet, og ADHD (oppmerksomhetssvikt-hyperaktivitets-syndromet) og annen bruk utenfor preparatomtale. De brukte også "falske rådgivende styrer, og tilsynelatende uavhengig medisinsk etterutdanning, (CME) programmer," og store bestikkelser i forbindelse med reiser for å fremme uautorisert bruk av legemidler. (...) (GSK illegally promoted bupropion for weight loss, sexual dysfunction, substance addictions, and attention-deficit/hyperactivity disorder and other off-label uses. It also used “sham advisory boards, and supposedly independent continuing medical education (CME) programs,” and lavish travel inducements to promote unauthorised uses of the drug.)

(Anm: Antidepressiva (nytteverdi) (mintankesmie.no).)

(Anm: Ny forskning: Lykkepiller gør mere skade end gavn. Folk med depression får intet ud af at tage antidepressivet SSRI, bedre kendt som lykkepiller, viser nyt dansk studie. (jyllands-posten.dk 13.2.2017).)

- Konklusjon: Dekonstruksjon av rettsdokumenter avslørte at protokollspesifikke resultater ikke viste statistisk signifikant forskjell mellom citalopram og placebo. Den publiserte artikkelen konkluderte imidlertid med at citalopram var trygt og betydelig mer effektivt enn placebo for barn og ungdom, med mulige bivirkninger mht. pasientsikkerhet.

(Anm: The citalopram CIT-MD-18 pediatric depression trial: Deconstruction of medical ghostwriting, data mischaracterisation and academic malfeasance. OBJECTIVE: Deconstruction of a ghostwritten report of a randomized, double-blind, placebo-controlled efficacy and safety trial of citalopram in depressed children and adolescents conducted in the United States. (…) CONCLUSION: Deconstruction of court documents revealed that protocol-specified outcome measures showed no statistically significant difference between citalopram and placebo. However, the published article concluded that citalopram was safe and significantly more efficacious than placebo for children and adolescents, with possible adverse effects on patient safety. Int J Risk Saf Med. 2016 Mar 16;28(1):33-43.)

(Anm: Cipralex (Lexapro) (escitalopram) - Cipramil (Celexa) (cipramil) (citalopram) - H. Lundbeck A/S (mintankesmie.no).)

(Anm: Forskere finner link mellom bruk av antidepressiva, medfødte misdannelser eller dødfødsler. (Researchers Find Link Between Antidepressant Use, Congenital Anomalies or Stillbirths) (…) "Mens denne ekstra risikoen kan virke liten er resultatene etter mitt syn så alvorlig som de kan være." (“While this extra risk may seem small, in my view, the outcomes are as serious as they can be.”) (dgnews.docguide.com 5.12.2016).)

(Anm: Eksponering av foster for antidepressiva kan endre Corpus Callosums mikrostruktur: Presentert ved PAS / ASPN. (…) Fordi "den neonate (nyfødtes) corpus callosum mikrostruktur er assosiert med utero (livmor) SSRI-eksponering og prenatal (før fødsel) mødredepresjon, er tidlige modningsprosesser i denne regionen følsomme for endret 5-hydroksytryptamin (5-HT) signalering under tiden i utero (livmor)," bemerket Campbell. "Disse resultatene - sammen med forstyrret hvit substans’ mikrostruktur i genu hos premature spedbarn - tyder dette på at utviklingen av [corpus callosum] kan være følsom for tidlige uheldige påvirkninger. (Fetal Exposure to Antidepressants May Alter Corpus Callosum Microstructure.) (dgnews.docguide.com 10.5.2017).)

(Anm: Unormal sæd med SSRI antidepressiva. Flere studier har funnet endrede sædparametere etter eksponering for SSRI-antidepressiva. Selv om SSRIs rolle er usikker, er det berettiget å ta hensyn til de observerte effektene på sædkvalitet og informere eksponerte pasienter. (Semen abnormalities with SSRI antidepressants. Several studies have found altered semen parameters after exposure to SSRI antidepressants. Although the role of SSRIs is uncertain, it is justified to take into account the observed effects on sperm quality and to inform exposed patients.) Prescrire Int 2015; 24 (156): 16-17.)

(Anm: Gravide kvinner som tar antidepressiva er mer sannsynlig å få barn med autisme, ifølge studie. Pregnant women who take antidepressants more likely to have a child with autism, study finds. Research data published in the BMJ reveal that antidepressant use during pregnancy increases the risk of autism in children, as reported The Independent Thursday. (firstwordpharma.com 20.7.2017).)

(Anm: - Nye data viser økt risiko for misdannelser når antidepressiva brukes under graviditet. (…) En studie publisert i British Medical Journal (BMJ) avslører at antidepressiva forskrevet til gravide kan øke sjansen for å få en baby med misdannelser.) (New Data Show Heightened Risk of Birth Defects When Antidepressants Are Used During Pregnancy.) (dgnews.docguide.com 19.1.2017).)

(Anm: - Utviklingen av et potensielt livstruende serotonergt syndrom eller nevroleptisk malignt syndrom (NMS)-lignende reaksjoner er rapportert for SNRI-er og SSRI-er alene, inkludert Celexa-behandling, men spesielt ved samtidig bruk av serotonerge legemidler (inklusive triptaner) og legemidler som svekker metabolisme av serotonin (inklusive MAO-hemmere), eller med antipsykotika eller andre dopaminantagonister (fda.gov 6.3.2009).)

(Anm: Antidepressant use during pregnancy and the risk of major congenital malformations in a cohort of depressed pregnant women: an updated analysis of the Quebec Pregnancy Cohort. (…) Conclusions Antidepressants with effects on serotonin reuptake during embryogenesis increased the risk of some organ-specific malformations in a cohort of pregnant women with depression. BMJ Open 2017;7:e013372.)

(Anm: Bruk av antipsykotika er assosiert med en 60 % økt risiko for dødelighet hos pasienter med Alzheimers sykdom. (…) Bruk av to eller flere antipsykotika samtidig ble knyttet til nesten doblet dødsrisiko (200 %) enn ved monoterapi.) (Antipsychotic Drug Use Increases Risk of Mortality Among Patients With Alzheimer’s Disease. JOENSUU, Finland -- December 12, 2016 -- Antipsychotic drug use is associated with a 60% increased risk of mortality among patients with Alzheimer's disease, according to a study published in the Journal of Alzheimer’s Disease. The risk was highest at the beginning of drug use and remained increased in long-term use. Use of 2 or more antipsychotic drugs concomitantly was associated with almost 2 times higher risk of mortality than monotherapy.) (dgnews.docguide.com 12.12.2016).)

(Anm: Antipsykotika dobler dødsrisiko allerede etter 180 dagers bruk. Greater Mortality Risk With Antipsychotics in Parkinson's (Større dødsrisiko med antipsykotika ved Parkinsons) (medicalnewstoday.com 21.6.2015).)

(Anm: (...) For ytterligere å illustrere problemet kan nevnes at antipsykotika forårsaker parkinsonisme (5), og en studie fant at mennesker med Parkinsons sykdom og psykose hadde fire ganger større sannsynlighet for å dø etter tre til seks måneders behandling enn de som ikke fikk antipsykotika. (6) De var også mer utsatt for kognitiv svikt, forverring av parkinsonsymptomer, hjerneslag, infeksjoner og fall. RE: Psykisk syke lever kortere. Tidsskr Nor Legeforen 10.11.2015.)

(Anm: Legemidler som kan gi delirium hos eldre. Delirium ses særlig hos eldre ved akutte sykdommer og skader eller som følge av toksisk eller farmakologisk påvirkning. Eldre personer har mange sykdommer og bruken av legemidler er høy. Mange legemidler, og særlig de med antikolinerg eller dopaminerg effekt, kan gi delirium. Kjennskap til legemidler og kombinasjoner av legemidler som kan gi delirium, er viktig for å kunne forebygge og behandle tilstanden. Tidsskr Nor Legeforen 2005; 125:2366-7 (8.9.2005).)

(Anm: Delirium in hospitalized patients: Risks and benefits of antipsychotics. ABSTRACT Consensus panel guidelines advocate for the judicious use of antipsychotic drugs to manage delirium in hospitalized patients when nonpharmacologic measures fail and the patient is in significant distress from symptoms, poses a safety risk to self or others, or is impeding essential aspects of his or her medical care. Here, we review the use of haloperidol, olanzapine, quetiapine, risperidone, and aripiprazole for this purpose. Cleveland Clinic Journal of Medicine. 2017 August;84(8):616-622.)

(Anm: Post injektionssyndrom. (…) De fleste af disse patienter udviklede symptomer på sedation (fra mild sedation til koma) og/eller delirium (herunder forvirring, desorientering, ophidselse/ uro, angst og anden kognitiv svækkelse). Andre symptomer inkluderede ekstrapyramidale symptomer, dysartri, ataksi, aggression, svimmelhed, svaghed, hypertension eller krampe.) (sundhedsstyrelsen.dk 29.6.2014).)

(Anm: Mødre til børn med misdannelser har øget dødelighed. (…) Bivirkninger har ført til to dødsfald. Den største del af bivirkningerne (42 procent) af de 429 blev indberettet for såkaldte psykostimulerende lægemidler - eksempelvis til behandling af ADHD - efterfulgt af 31 procent for antidepressiver og 24 procent for antipsykotiske lægemidler. (videnskab.dk 20.12.2016).)

(Anm: Antikolinerge effekter av vanlige legemidler knyttet til økt dødelighet hos mennesker over 65. De kombinerte antikolinerge effektene av mange vanlige legemidler øker risikoen for kognitiv svekkelse og død hos personer over 65 år, ifølge resultater fra en storskala studie på den langsiktige helseeffekten av legemidler.(Anticholinergic effects of common drugs are associated with increased mortality in over 65s. The combined anticholinergic effects of many common drugs increase the risk of cognitive impairment and death in people aged over 65, a large scale study of the long term effect of drugs on health has found.) BMJ 2011; 342:d4037 (28 June).)

(Anm: Men experience greater cognitive impairment and increased risk of death following hip surgery. In a study of hip fracture patients, men displayed greater levels of cognitive impairment within the first 22 days of fracture than women, and cognitive limitations increased the risk of dying within six months in both men and women. "While men make up only about 25 percent of all hip fractures, the number of men who fracture their hip is increasing and we know men are more likely to die than women after a hip fracture," said Dr. Ann Gruber-Baldini, lead author of the Journal of the American Geriatrics Society study. (medicalnewstoday.com 10.2.2017).)

(Anm: Det autonome nervesystemet. Det autonome nervesystemets hovedoppgave er å bidra til likevekt i kroppens basale funksjoner. Det vil blant annet si kroppstemperatur, blodtrykk, åndedrett og fordøyelse. (nhi.no 4.3.2015).)

(Anm: Ulike selektive serotonin reopptakshemmeres (SSRI-er) cytotoksisitet mot kreftceller. (Cytotoxicity of different selective serotonin reuptake inhibitors (SSRIs) against cancer cells.) (…) Vi har funnet at paroxetine (paroksetin; Seroxat; Paxil etc.) har cytotoksisk aktivitet mot tumorceller. J Exp Ther Oncol. 2006;6(1):23-9.)

(Anm: Could antidepressants stop prostate cancer from spreading? In almost all cases where prostate cancer spreads to other areas of the body, the disease spreads to the bone first. In a new study, researchers reveal the discovery of an enzyme that helps prostate cancer cells to invade bone. Furthermore, certain antidepressant medications may have the potential to block this enzyme. Study co-author Jason Wu, of Washington State University-Spokane, and colleagues recently reported their findings in the journal Cancer Cell. (medicalnewstoday.com 13.3.2017).)

(Anm: Classic cytotoxic drugs: a narrow path for regulatory approval. Several classic cytotoxic drugs have shown encouraging activity in the treatment of metastatic breast cancer.1–3 However, only a few have received an overwhelming welcome from regulatory authorities and succeeded in obtaining widespread regulatory approval for routine use. For example eribulin was approved for treatment of metastatic breast cancer in several countries including Japan, USA, and Europe, based on data that showed longer overall survival in patients treated with eribulin compared with patients treated with physician's choice of treatment. In contrast ixabcpilone with capecitabine gained approval from the US Food and Drug Agency based on data showing longer progression-free survival compared with capccitabine alone, but did not obtain rcgulatory authorisation in Europc because it is associated with a high incidence of nevropathy.5 Lancet Oncol. 2017 Feb 10. pii: S1470-2045(17)30089-X. [Epub ahead of print].)

(Anm: Ødelagt cellulær "klokke" linket til hjerneskade (Broken Cellular 'Clock' Linked to Brain Damage) (sciencedaily.com 25.11.2013).)

(Anm: Signaling Pathways Linked to Serotonin-Induced Superoxide Anion Production: A Physiological Role for Mitochondria in Pulmonary Arteries. Abstract. Serotonin (5-HT) is a potent vasoconstrictor agonist and contributes to several vascular diseases including systemic or pulmonary hypertension and atherosclerosis. Although superoxide anion ([Formula: see text]) is commonly associated to cellular damages due to [Formula: see text] overproduction, we previously demonstrated that, in physiological conditions, [Formula: see text] also participates to the 5-HT contraction in intrapulmonary arteries (IPA). Front Physiol. 2017 Feb 9;8:76. eCollection 2017.)

(Anm: Bruk av antidepressiva ble assosiert med et betydelig eldre utseende og forskere fant også ut at vekten spilte en viktig faktor. I de sett med tvillinger som var yngre enn 40 år ble tyngre tvillinger oppfattet som eldre. (…) I tillegg mistenker forskerne at den vedvarende avslapping av ansiktsmuskler som antidepressiva forårsaker kan forklare årsaken til at ansiktet faller sammen (henger). (mintankesmie.no).)

(Anm: Minislag (ministroke: transient ischemic attack (TIA)) linket til lavere forventet levetid. (- Minislag kan forårsake demens.) (- Enkelte psykofarmaka kan øke risiko for minislag / demens.) (mintankesmie.no).)

(Anm: Stumme infarkt rammer oftere folk med høy smertetoleranse. Stumme hjerteinfarkt gir ikke de klassiske brystsmertene som ved vanlige infarkt. - Denne pasientgruppen tar enten ikke kontakt med lege, eller de har ikke fått riktig diagnose, sier lege og forsker Andrea Milde Øhrn. (…) Det er vanlig å tenke sterke brystsmerter og akutt behandling når det er snakk om hjerteinfarkt. Det mange kanskje ikke vet, er at man kan ha hatt et hjerteinfarkt uten å vite det. Dette kalles et stumt infarkt, et hjerteinfarkt med få eller ingen symptomer. - Et stumt hjerteinfarkt er et hjerteinfarkt som ikke er erkjent. (nhi.no 3.2.2017).)

(Anm: Sannsynlig karotidyni forårsaket av fluoxetine (Prozac; SSRI-er). (Probable fluoxetine-induced carotidynia.)  Karotidyni er en fokal nakkesmerte (bestemt, avgrenset område), som involverer anatomiske områder til den berørte arteria carotis, og stråler ofte ut i den ipsilateral side (samme side) av ansiktet eller øret. På grunnlag av medisinsk historie og alder har karotidyni konvensjonelt vært klassifisert i klassisk (ikke-migrenøs), migrenøs, og vaskulære varianter. The Lancet 2009;374(9695):1061-1062 (26 September).)

(Anm: Nakkesmerter sætter forskerne skakmat. Kroniske nakkesmerter koster samfundet milliarder og er en af de hyppigste årsager til, at danskere melder sig syge fra job. Forskerne er i vildrede: Ingen behandling er effektiv. (videnskab.dk 22.12.2016).)

(Anm: Antidepressiva linket til hjerterisiko: tvillingstudie. (Antidepressants linked to heart risk: twins study) - Middelaldrende menn som bruker antidepressiva er mer sannsynlig å ha en innsnevring av blodårer, noe som øker risikoen for hjerteinfarkt og slag, enn de som ikke bruker legemidlene, ifølge en studie presentert på lørdag. (Reuters) - Middle-age men who use antidepressants are more likely to have a narrowing of blood vessels, increasing the risk of heart attacks and strokes, than those who do not use the medications, according to a study presented on Saturday.) (reuters.com 2.4.2011).)

(Anm: - Pfizers Zyvoxid (Zyvox) og antidepressiva kan være en dødelig kombinasjon. (- Det antas at når linezolid gis til pasienter, som behandles med serotonerge psykofarmaka, kan forhøyede nivåer av serotonin bygge seg opp i hjernen og forårsake toksisitet (giftighet). Dette er referert til som Serotonin syndrom - tegn og symptomer inkluderer mentale endringer (forvirring, hyperaktivitet, minneproblemer), muskelrykninger, overdreven svetting, skjelving eller risting, diaré, problemer med koordinasjon og / eller feber.) (fda.gov 21.10.2011).)

(Anm: Hva er det forskrivere og pasienter ikke vet om bivirkninger av antidepressiva? (What do prescribers and patients not know about the side effects of antidepressant drugs?) (medicalnewstoday.com 15.9.2016).)

(Anm: Forskere: Alvorlige bivirkninger, når antidepressiver droppes. Angst, depression og selvmordstanker er nogle af de bivirkninger, som tit forekommer, når man holder op med at tage antidepressiv medicin. Bivirkningerne kan i nogle tilfælde være langvarige og kroniske, viser et nyt studie. (videnskab.dk 16.3.2015).)

(Anm: Bruk av visse smertestillende midler (og antidepressiva (+ 31 %)) forbundet med økt risiko for drap (Use of certain painkillers linked with increased risk of homicide) Enkelte legemidler som påvirker sentralnervesystemet - som smertestillende og beroligende benzodiazepiner - er assosiert med økt risiko for å begå et drap, finner en ny studie publisert i tidsskriftet World Psychiatry. (medicalnewstoday.com 1.6.2015).)

(Anm: Psykiatriske patienter ender i private botilbud. Drab og vold har de seneste år fyldt debatten om de danske bosteder for patienter med psykiske problemer. (…) Psykiatriske patienter ender i private botilbud. (…) Mens Folketinget kæmper for en løsning på problemet med vold på offentlige bosteder, vælger flere kommuner at sende tunge patienter til private tilbud. (politiken.dk 18.3.2017.)

(Anm: Aggresjon knyttet til økt risiko for substansmisbruk. Aggression disorder linked to greater risk of substance abuse. (…) In the study, published in the Journal of Clinical Psychiatry, Emil Coccaro, MD, and colleagues analyzed data from more than 9,200 subjects in the National Comorbidity Survey, a national survey of mental health in the United States. They found that as the severity of aggressive behavior increased, so did levels of daily and weekly substance use. The findings suggest that a history of frequent, aggressive behavior is a risk factor for later substance abuse, and effective treatment of aggression could delay or even prevent substance abuse in young people. (medicalnewstoday.com 2.3.2017).)

(Anm: Halvparten av norske drap begått av rusede. (…) I 125 av drapene – eller 54 prosent – er det beskrevet i dommen at gjerningspersonen var påvirket av rusmidler under drapet. (nrk.no 13.12.2016).)

- En pasient på UNN døde av blodforgiftning som følge av et legemiddel mot psykiske lidelser, opplyser Statens helsetilsyn.

(Anm: En pasient på UNN døde av blodforgiftning som følge av et legemiddel mot psykiske lidelser, opplyser Statens helsetilsyn. (- Pasienten døde etter kort tid, og dødsårsaken var nøytropen sepsis (blodforgiftning), heter det i tilsynets rapport. (nrk.no 12.10.2016).)

(Anm: Systemic inflammatory response syndrome (SIRS) is an inflammatory state affecting the whole body, frequently a response of the immune system to infection. (en.wikipedia.org).)

(Anm: Sepsis. Definisjon: SIRS + påvist/mistenkt infeksjon (f. eks. positiv blodkultur). SIRS- kriteriene er: - Feber > 38 ºC eller hypotermi < 36 ºC - Puls > 90/minutt - Respirasjonsfrekvens > 20/minutt eller hypokapni med pCO2 < 4,3 kPa i blodgass - Leukocytose ≥ 12 × 109/l eller leukopeni < 4 × 109/l eller > 10 % umodne leukocytter. (helsebiblioteket.no - Metodebok for indremedisinere, 2012).)

(Anm: Rollen til mitokondriell dysfunksjon (mitokondriedysfunksjon) ved sepsis (blodforgiftning)-indusert multiorgansvikt. (The role of mitochondrial dysfunction in sepsis-induced multi-organ failure). (Virulence. 2013 Nov 1;5(1).)

- Diagnostisering av sepsis. Sepsis, også kjent som blodforgiftning, er kroppens hyperaktive respons på en infeksjon som kan føre til betennelse, vevskader, organsvikt etc.

(Anm: Diagnosing Sepsis. Sepsis, also known as blood poisoning, is the body’s hyperactive response to an infection that can lead to inflammation, tissue damage, organ failure etc. It is a very dangerous state in which the immune system stops fighting with the invading agents  and turns to itself. Around one-third of patients who are affected with sepsis die every year. (news-medical.net 7.9.2017).)

- Å anerkjenne sepsis som en global helseprioritet - En WHO- resolusjon.

(Anm: Å anerkjenne sepsis som en global helseprioritet - En WHO- resolusjon. Recognizing Sepsis as a Global Health Priority — A WHO Resolution. “Some very important clinical issues, some of them affecting life and death, stay largely in a backwater which is inhabited by academics and professionals and enthusiasts, dealt with very well at the clinical and scientific level but not visible to the public, political leaders, leaders of healthcare systems... The public and political space is the space in which [sepsis] needs to be in order for things to change.” NEJM (June 28, 2017).)

(Anm: Sepsis – den dödliga sjukdomen som glöms bort. Trots att infektionssjukdomen sepsis förekommer oftare än de vanligaste formerna av cancer och att upp emot hälften som drabbas av den allvarligaste formen dör, så har många knappt hört talas om sjukdomen. Sepsis som är den medicinska termen på blodförgiftning, drabbar omkring 40 000 svenskar varje år. (netdoktor.se 7.6.2017).)

- Hurtigtest finner tegn på sepsis i en enkelt dråpe blod.

(Anm: Hurtigtest finner tegn på sepsis i en enkelt dråpe blod. (- Sepsis, en potensielt livstruende komplikasjon av en infeksjon, har den høyeste byrde mht. død og medisinske utgifter på sykehus over hele verden.) (- Quick test finds signs of sepsis in a single drop of blood. (…) Sepsis, a potentially life-threatening complication of an infection, has the highest burden of death and medical expenses in hospitals worldwide. (medicalnewstoday.com 5.7.2017).)

(Anm: Nye sepsiskriterier kan føre til forsinket behandling. (…) Sepsis er en svært alvorlig tilstand med høy morbiditet og mortalitet (2). Den totale insidensen er ukjent, men man regner med at sepsis er en av de viktigste årsakene til alvorlig, akutt sykdom på verdensbasis (1). (…) Sepsis har inntil nylig vært definert som mistenkt infeksjon med samtidig tilstedeværelse av to eller flere SIRS-kriterier (1). Endringer i hjertefrekvens, kroppstemperatur, respirasjonsfrekvens og leukocytter er kroppens tegn på inflammasjon, og de indikerer ikke nødvendigvis en livstruende, dysregulert vertsrespons på infeksjon. Tidsskr Nor Legeforen 2017; :609-10 (20.4.2017).)

(Anm: LEGENE FORSTO IKKE AT HAN VAR DØDSSYK: Stian (19) døde etter 18 timer på sykehus uten legetilsyn. (…) Helsetilsynet konkluderer med at sykehusets behandling var uforsvarlig. (…) Fikk ikke beskjed. (…) Fastlegen sendte med dem papirer som foreldrene leverte på Akuttmottaket ved Ahus, der sto det; «Diagnose: Obs sepsis».  (tv2.no 29.4.2017).)

(Anm: Svikt i behandlingen av akutt syk ung mann i akuttmottaket – brudd på helselovgivningen. (…) Pasienten ble lagt på observasjonsposten (Akutt 24) ved akuttmottaket frem til neste morgen. I løpet av tiden på observasjonsposten ble han ikke tilsett av lege. På morgenen var han betydelig verre og han fikk tegn på fullt utviklet blodforgiftning. Behandling med antibiotika ble iverksatt, men han døde kort tid etter som følge av meningokokksepsis og hjerneødem. (helsetilsynet.no 2.5.2017).)

(Anm: Sepsis; grunnleggende kliniske observasjoner. Sepsis= En systemisk inflammatorisk respons (SIRS) pga. en infeksjon Tre alvorlighetsgrader: 1) Sepsis (to eller flere symptomer på SIRS som følge av infeksjon) 2) Alvorlig sepsis (sepsis med akutt organdysfunksjon, hypoperfusjon eller hypotensjon) 3) Septisk sjokk (hypotensjon til tross for adekvat væsketerapi, samt forekomst av perfusjonsforstyrrelser og organdysfunksjon) (hnt.no 5.11.2013).)

- Alle bryt lova i behandling av blodforgifting. Pasientar med alvorleg blodforgifting (sepsis) blir undersøkt av lege for seint.

(Anm: Alle bryt lova i behandling av blodforgifting. Pasientar med alvorleg blodforgifting blir undersøkt av lege for seint. Helsetilsynet fann brot ved 24 akuttmottak over heile landet. – Svært alvorleg. – Dette er svært alvorleg, for det dreier seg om ein alvorleg infeksjonssjukdom som i verste fall kan medføra død dersom behandlinga ikkje blir igangsett til riktig tid, seier avdelingsdirektør i Helsetilsynet, Ragnar Hermstad. OVER EIN TIME: Pasientar som kjem inn med teikn på alvorleg infeksjonssjukdom som blodforgifting skal ifølge nasjonale retningslinjer få anitibiotikabehandling innan maks ein time. Alle dei 24 akuttmottaka hadde svikt på dette området. (nrk.no 16.6.2017).)

(Anm: Lege sier improvisert «kur» for sepsis har hatt bemerkelsesverdige resultater. (…) Spesialist i intensivbehandling Paul Marik sier at enkel behandling med infusjon av vitamin C og steroider har bemerkelsesverdig effekt på pasienter med potensielt dødelig tilstand. (independent.co.uk 24.3.2017).)

(Anm: Bivirkninger underrapporteres i videnskabelige tidsskrifter. (...) Mellem 43 og 100 procent af de bivirkninger, der, ifølge det ikke-publicerede materiale, er fundet ved de testede lægemidler, er ikke lagt frem i de videnskabelige artikler, viser Yoon Loke og kollegernes gennemgang. (videnskab.dk 5.10.2016).)

(Anm: Dødsfall på grunn av nøytropen sepsis (blodforgiftning) etter behandling med legemiddelet klozapin – uforsvarlig oppfølging – mangelfull samhandling og informasjon. (…)  Manglende informasjon fra spesialisthelsetjenesten og mangelfull samhandling mellom kommunehelsetjenesten, fastlegen, pasienten og pårørende bidro til hendelsen. Helseforetaket skal gjennomgå hendelsen for å redusere risikoen ved lignende tilfeller. (helsetilsynet.no 12.10.2016).)

(Anm: Eksplosjon av antidepressiva til unge jenter. De ønsker psykologhjelp. I stedet blir de fôret med piller fra fastlegen. Unge jenter har aldri brukt mer antidepressiver. (vg.no 10.9.2016).)

(Anm: Flere barn og unge akuttinnlegges for psykisk sykdom. I fjor utgjorde andelen øyeblikkelig hjelp innleggelser 61 prosent av alle innleggelser. Det er en økning fra 47 prosent i 2012. (dagensmedisin.no 19.9.2016).)

(Anm: Eksplosjon av antidepressiva til unge jenter: Lykkepillegenerasjonen. «Lykkepillen» gjorde Sandra så dårlig at hun ble innlagt på psykiatrisk avdeling. På ti år har bruken av antidepressiver blant unge jenter økt med 83 prosent. Mange får pillene uten en gang å ha snakket med psykolog.  (vg.no 10.9.2016).)

(Anm: Helseminister Bent Høie reagerer på «lykkepille»-praksis: – Veldig urovekkende. ** Kraftig økning i antidepressiva til unge jenter. Helseminister Bent Høie reagerer på den sterke økningen i lykkepillebruk blant unge jenter. Han mener manglende ressurser og fastlegers holdninger er årsaker. Lørdag dokumenterte VG Helg og VG+ konsekvensene av den økende lykkepille-bruken blant unge jenter. (vg.no 10.9.2016).)

(Anm: LO advarer mot trygdebombe. En stadig større del av nordmenn i arbeidsfør alder er uten jobb. LO mener dette er en potensiell trygdebombe. (…) Det trengs 180.000 nye jobber for å få yrkesdeltakelsen opp på samme nivå som i 2008, viser en rapport fra samfunnsøkonomene i LO. I 2008 var 70 prosent av befolkningen mellom 15 og 74 år i jobb. Nå er yrkesdeltakelsen nede i 67,3 prosent., og det er nedgang i alle fylker. (hegnar.no 6.10.2016).)

(Anm: Rekordmange søger akut psykisk hjælp. (- Mens kun 12.099 danskere i 1995 besøgte de psykiatriske akutmodtagelser og skadestuer, er det steget til hele 33.333 i 2015, viser opgørelse fra Sundhedsdatastyrelsen og Danske Regioner, der for kort tid siden blev sendt til Folketinget. (politiken.dk 9.7.2016).)

(Anm: Har vi blitt psykisk sykere? (- Vi vet også at stadig flere får uførepensjon på grunn av psykiske lidelser og at sykefraværet på grunn av psykiske plager og lidelser har økt. Vi tror alle disse forholdene bidrar til vår oppfatning om at stadig flere får en psykisk lidelse eller plage.) (Folkehelseinstituttet fhi.no 10.10.2013).)

(Anm: Høyt fravær på grunn av ME. Minst 270 elever var borte fra skolen i fjor fordi de hadde ME. (aftenposten.no 6.2.2017).)

(Anm: Psykisk ohälsa fortsätter att öka. Antalet svenskar som sjukskrivs på grund av psykisk ohälsa ökar kontinuerligt sedan 2010. Den vanligaste diagnosen är stressrelaterad psykisk ohälsa som till mångt och mycket är arbetsrelaterad. Då evidensbaserad behandling saknas står förebyggande arbete i fokus. (netdoktor.se 14.9.2016).)

(Anm: Psykiatriske skadestuer kan ikke klare presset. Psykiske lidelser hører til nogle af de største sygdomsbyrder, som hvert år koster samfundet et svimlende milliardbeløb i tabt arbejdsfortjeneste og sociale ydelser. (politiken.dk 11.7.2016).)

(Anm: - 9 ting som skjer i hjernen og kroppen på MDMA (Ecstasy). (- 9 Things That Happen in the Brain and Body on MDMA.) (- Derfor, når substansen avsluttes, sitter mennesker igjen med mindre serotonin enn vanlig, noe som kan føre til følelser av depresjon, irritabilitet og tretthet.) (- Siden MDMA frigir så mye serotonin, ødelegger kroppen deretter mer serotonin enn vanlig, ifølge AsapSCIENCE.) (thescienceexplorer.com 24.6.2016).)

- GlaxoSmithKline erklærer seg skyldig og betaler 18 milliarder kroner for ulovlig markesføring

GlaxoSmithKline settles fraud case for $3 billion (GlaxoSmithKline forliker svindelsak for 3 milliarder dollar)
reuters.com 2.7.2012
(Reuters) - GlaxoSmithKline Plc has agreed to plead guilty to criminal charges and pay $3 billion to settle the largest case of healthcare fraud in U.S. history, according to court filings and prosecutors.

The settlement includes $1 billion in criminal fines and $2 billion in civil fines in connection with the sale of the drug company's Paxil, Wellbutrin and Avandia products.

Deputy U.S. Attorney General James Cole said on Monday that the settlement "is unprecedented in both size and scope."
As part of the settlement, GlaxoSmithKline agreed to strict oversight of its sales force by the U.S. government to prevent the use of kickbacks or other prohibited practices. (...)

(Anm: Seroxat (Paxil) (paroxetine; paroksetin) (SSRI) (mintankesmie.no).)

(Anm: Avandia (rosiglitazone) - informasjon versus kunnskap og visdom - hvem visste hva? (mintankesmie.no).)

(Anm: Novartis agrees to pay $390m in US kickback case. Novartis AG, the Swiss drug company, has agreed to pay $390m (£255m; €352m) to settle a lawsuit in which the US government claimed that the company had paid kickbacks to specialty pharmacies to boost sales of its drugs. The lawsuit filed by the US Department of Justice had initially sought $3.35bn in fines and damages, charging that the kickback scheme had led the pharmacies to submit false claims for tens of millions of dollars to Medicare and Medicaid programs. BMJ 2015;351:h5784 (Published 28 October 2015).)

Legemiddelgigant får milliardbot i USA
aftenposten.no 2.7.2012
Legemiddelfirmaet GlaxoSmithKline er bøtelagt for svindel etter feilmerking av antidepressiva. Forliket er det største av sitt slag innen det amerikanske helsevesenet.

GSK ble bøtelagt for å ha feilmerket de antidepressive medikamentene Paxil og Wellbutrin. Bruken av legemidlene, blant annet til behandling av barn og unge, var ikke godkjent av amerikanske myndigheter.

Legemiddelfirmaet erklærte seg skyldig og innrømmet i tillegg å ha holdt tilbake informasjon og kommet med uberettigede påstander om sikkerheten ved bruk av diabetesmedisinen Avandia.

GSK fikk tre bøter på til sammen tre milliarder dollar, nesten 18 milliarder kroner.

- I altfor lang tid har vi hørt at farmasøytisk industri anser disse forlikene som forretningskostnader, sier konstituert visejustisminister Stuart Delery og priser det høye forliket.

Styreleder i GSK, Andrew Witty, sier i en uttalelse at firmaet nå har fundamentalt forandret sine fremgangsmåter innen markedsføring og salg.
Firmaet står blant annet også bak svineinfluensavaksinen Pandemrix. (...)

(Anm: Seroxat (Paxil) (paroxetine; paroksetin) (SSRI) (mintankesmie.no).)

(Anm: Avandia (rosiglitazone) - informasjon versus kunnskap og visdom - hvem visste hva? (mintankesmie.no).)

GSK pleads guilty and pays $3 billion for illegal promotion (GSK erklærer seg skyldig og betaler 3 milliarder dollar for ulovlig markesføring)
pharmatimes.com 3.7.2012
In the largest healthcare fraud settlement in US history, GlaxoSmithKline has confirmed it will pay $3 billion in fines for unlawful promotion of the antidepressant drugs Paxil and Wellbutrin and for failing to report safety data about its controversial diabetes drug Avandia. (...)

Factbox: Large drug industry settlements with U.S. government
reuters.com 2.7.2012
(Reuters) - British drugmaker GlaxoSmithKline said on Monday it agreed to pay $3 billion in U.S. fines for illegally promoting its antidepressant drugs Paxil and Wellbutrin for unapproved uses, and for failing to report safety data about its diabetes drug Avandia. The settlement represents the largest ever in the drug industry, topping the $2.3 billion in fines paid by Pfizer on similar charges in 2009.

Here are some of the largest prosecutions of the last 10 years:

* Pfizer Inc in 2009 pleaded guilty to a U.S. criminal charge relating to promotion of its now-withdrawn Bextra pain medicine and agreed to pay a record $2.3 billion to settle allegations it improperly marketed 13 drugs.
* Eli Lilly and Co in January 2009 said it would pay $1.42 billion to settle probes into selling its Zyprexa schizophrenia drug for unapproved uses, a practice known as "off-label" marketing. Lilly agreed to plead guilty to a federal misdemeanor.
* Merck & Co in February 2008 reached an agreement to pay more than $650 million to resolve allegations that it failed to pay Medicaid and other government healthcare programs owed rebates for cholesterol drug Zocor and pain reliever Vioxx. The company also settled charges that it paid kickbacks to healthcare providers so they would prescribe its drugs.
* Bristol-Myers Squibb agreed in September 2007 to pay more than $510 million to settle charges of illegal marketing and pricing for its products. That included allegations that the company paid and offered gifts to doctors and healthcare providers to entice them to buy their drugs and also promoted certain medicines for uses that were not approved by the Food and Drug Administration.
* Cephalon agreed in September 2008 to pay $425 million to settle allegations that it marketed three drugs for uses that were not approved. (...)

(Anm: Seroxat (Paxil) (paroxetine; paroksetin) (SSRI) (mintankesmie.no).)

(Anm: Avandia (rosiglitazone) - informasjon versus kunnskap og visdom - hvem visste hva? (mintankesmie.no).)

Glaxo in $3 Billion Settlement
online.wsj.com 2.7.2012
Drug maker GlaxoSmithKline PLC agreed to plead guilty to criminal charges of illegally marketing drugs and withholding safety data from U.S. regulators, and to pay $3 billion to the government in what the Justice Department called the largest health-care fraud settlement in U.S. history.

Under the deal, which requires court approval, Glaxo will plead guilty to criminal charges involving three drugs—the antidepressants Paxil and Wellbutrin and the diabetes drug Avandia. The settlement includes $1 billion in criminal fines and $2 billion to resolve civil liabilities owed to the federal government and the states, the Justice Department said. Glaxo had announced ...

Drug maker GlaxoSmithKline PLC agreed to plead guilty to criminal charges of illegally marketing drugs and withholding safety data from U.S. regulators, and to pay $3 billion to the government in what the Justice Department called the largest health-care fraud settlement in U.S. history.
Under the deal, which requires court approval, Glaxo will plead guilty to criminal charges involving three drugs—the antidepressants Paxil and Wellbutrin and the diabetes drug Avandia. The settlement includes $1 billion in criminal fines and $2 billion to resolve civil liabilities owed to the federal government and the states, the Justice Department said. Glaxo had announced (...)

(Anm: Seroxat (Paxil) (paroxetine; paroksetin) (SSRI) (mintankesmie.no).)

(Anm: Avandia (rosiglitazone) - informasjon versus kunnskap og visdom - hvem visste hva? (mintankesmie.no).)

- Forest betaler 313 millioner dollar for å forlike granskning av forskrivvning utenfor preparatomtale

Forest pays $313 million to settle off-label promotion probe (Forest betaler 313 millioner dollar for å forlike granskning av forskrivvning utenfor preparatomtale)
pharmatimes.com 16.9.2010
The company has finalised an agreement-in-principle to resolve all aspects of the investigations led by the Department of Justice and the Attorney's Office for Massachusetts that began in January 2004. The probe related to Forest's marketing of the antidepressants Celexa (citalopram) and Lexapro (escitalopram) and an unapproved formulation of the thyroid treatment Levothroid (levothyroxine).

Forest is paying out $313 million plus interest and is pleading guilty to a single felony charge relating to misstatements by certain employees to US Food and Drug Administration inspectors during a November 2003 plant inspection. It also agreed to plead guilty to two violations of the Food, Drug and Cosmetic Act involving off-label promotion.

The company has also entered into a corporate integrity agreement with the Office of Inspector General of the US Department of Health and Human Services. It requires Forest to maintain its current compliance programme and to undertake "a set of defined corporate integrity obligations for a period of five years". (...)

- Profitt uten grenser

Profitt uten grenser
MINILEDER
Tidsskr Nor Legeforen 2012; 132:1053 (15.5.2012)
«A promise for life - turning science into caring» er legemiddelselskapet Abbotts motto. Et sted på veien må dette løftet være blitt glemt. Mandag 7. mai kunngjorde selskapet at de vil betale en bot på 1,6 milliarder dollar, altså nesten 10 milliarder kroner, i forbindelse med ulovlig markedsføring av Depakote, et antiepileptikum. Legemidlet er markedsført og solgt langt utenfor de indikasjoner det er godkjent for, bl.a. til gamle, til demente og til autistiske barn. Dette har ikke skjedd i vanvare, men som følge av en bevisst salgsstrategi over flere år.

Abbott er ikke alene. I fjor måtte GlaxoSmithKline betale 3 milliarder dollar i bøter og erstatninger for misvisende markedsføring av bl.a. Avandia, og Merck (MSD) godtok en bot på nesten 1 milliard dollar for villedende markedsføring av Vioxx. Denne summen kom i tillegg til de nesten 5 milliarder dollar selskapet tidligere har betalt ut i erstatninger. Pfizer måtte betale 2,3 milliarder dollar i 2009. Men vil bøtene hjelpe? De utgjør bare en brøkdel av selskapenes profitt på legemidlene. (...)

- Again and again, the lure of increased sales overcomes the threat of potential penalties (Igjen og igjen overvinner fristelsen om økt salg trusselen om potensielle straffer)

The limits of free speech
nature.com 19.12.2012 (Nature | Editorial)
Uregulert legemiddelmarkedsføring kveler vitenskap og skader pasienter. Å antyde noe annet er en fornærmelse mot friheten - ikke en beskyttelse av den. (Unregulated drug marketing stifles science and harms patients. To suggest otherwise is an affront to liberty — not a protection of it.)

On 12 December, American drug giant Pfizer agreed to pay the US government more than US$55 million in fines. Wyeth, a pharmaceutical company now owned by Pfizer, had overstated the benefits of its proton-pump inhibitor Protonix (pantoprazole), despite repeated warnings from the US Food and Drug Administration (FDA).

A government prosecutor said that the exaggerations were intentional and planned: “Wyeth tried to cheat the system by obtaining a limited FDA approval for Protonix, fully intending to promote this drug for additional, unapproved uses.”

Samlet har legemiddelfirmaene betalt milliarder av dollar for tilsvarende overtredelser. Igjen og igjen overvinner fristelsen om økt salg trusselen om mulige straff. (...) (Collectively, drug companies have paid billions of dollars for similar offences. Again and again, the lure of increased sales overcomes the threat of potential penalties.)

- Leger ofte uvitende om status på legemidlers godkjennelse

Doctors Often Unaware of Drugs' Approval Status (Leger ofte uvitende om status på legemidlers godkjennelse)
Medpagetoday.com 21.8.2009
Physicians frequently prescribe medications for off-label uses, mistakenly believing there's FDA approval for those indications, according to a survey of clinicians.
More than 40% of respondents believed one or more drugs had FDA approval for indications that have uncertain or no supporting evidence, said G. Caleb Alexander, MD, of the University of Chicago, and colleagues.

Overall, the survey participants knew the FDA approval-status for about half of 14 drug-indication pairs, such as gabapentin (Neurontin) for diabetic neuropathy (off label, some supporting evidence), they reported online in Pharmacoepidemiology and Drug Safety. (...)

(Anm: U.S. physician knowledge of the FDA-approved indications and evidence base for commonly prescribed drugs: results of a national survey. Pharmacoepidemiol Drug Saf 2009; DOI: 10.1002/pds.1825.)

Okunskap bakom förskrivning
lakemedelsvarlden.se 24.8.2009
Kunskapen om FDA:s indikationer för läkemedel tycks vara bristfällig bland amerikanska allmänläkare och psykiatriker. Den behöver i alla fall förbättras anser forskare som undersökt läkarnas kunskaper i ämnet.

OFF-LABEL Att läkare förskriver en behandling som läkemedlet inte godkänts för är vare sig olagligt eller ovanligt, men skälet till varför är ibland oklart.
Enligt en amerikansk studie som omfattar drygt 1000 allmänläkare och psykiatriker tycks ett svar på varför det är så vara att läkarna tror att läkemedlet är godkänt för den behandling man förskrivit det för. Okunskap alltså. (...)

- Flere barn går på ikke-godkjent sovemedisin (– Urovekkende, sier norsk psykiater.)

Flere barn går på ikke-godkjent sovemedisin
nrk.no 4.5.2015
Bruk av hormonet melatonin som sovemedisin for barn og unge øker, men medisinen er ikke godkjent til dette. Det er lite forskning på langsiktige bivirkninger. – Urovekkende, sier norsk psykiater. (…)

Barn helt ned i fireårsalderen tar slike piller i flere år, selv om medisinene bare er godkjent for folk over 55 i perioder på 13 uker, viser en ny studie. (…)

Dyrestudier har vist at melatonin-stoffer kan virke inn på kjønnsutvikling og fruktbarhet hos ulike pattedyr. Forsøkene viste at melatonin kan føre til forsinket pubertet hos noen dyrearter. (…)

Men leger har fortsatt lov til å skrive ut resepter til barn og unge.

– Dette er en helt nødvendig sikkerhetsventil, sier Steinar Madsen om legenes rett til å skrive ut ikke-godkjente medisiner. Han er medisinsk fagdirektør i Statens Legemiddelverk.

Noen ganger ser legene det som nødvendig å skrive ut et legemiddel, selv om det ikke er godkjent for den bestemte bruken. Grunnen til at et legemiddel ikke er godkjent for visse befolkningsgrupper, kan noen ganger være at det er etisk vanskelig å teste ut, ifølge helsebiblioteket. En slik gruppe er barn. (…)

(Anm: Potential safety issues in the use of the hormone melatonin in paediatrics.J Paediatr Child Health. 2015 Feb 3. [Epub ahead of print].)

- 13 000 barn får søvnhormonet Melatonin. I overkant av 17.000 barn og unge har resept på piller som skal gjøre dem søvnige.

(Anm: 13 000 barn får søvnhormonet Melatonin. I overkant av 17.000 barn og unge har resept på piller som skal gjøre dem søvnige. Da Caroline Yin (18) hadde slitt med søvnløshet i et halvt år, fikk hun den reseptbelagte innsovingsmedisinen Melatonin. En «quick fix», mener søvnforsker Børge Sivertsen.  (vg.no 29.6.2017).)

(Anm: Mange norske barn går på ikke-godkjent sovemedisin i flere år. Bruk av hormonet melatonin som sovemedisin for barn og unge øker, men medisinen er ikke godkjent til dette. Det er lite forskning på langsiktige bivirkninger.  – Urovekkende, sier norsk psykiater. (forskning.no 4.5.2015).)

- Behandler ADHD med sovemedisin som ikke er godkjent

Behandler ADHD med sovemedisin som ikke er godkjent
nrk.no 27.2.2012
Sovemidler som inneholder melatonin blir ofte benyttet under behandling av barn med ADHD.

Antall ungdommer som får sovemidler på resept har doblet seg siden 2005. Store deler av medisinene brukes til behandling av barn og unge med ADHD.

– Dette er kanskje ikke helt bra. Dette er en behandling utenom det som er godkjent av legemiddelverket, sier avdelingsoverlege Steinar Madsen i avdeling for legemiddelinformasjon hos Statens legemiddelverk.

Bruken av sovemidler blant barn og unge i alderen 10–19 år har mer enn doblet seg siden 2005. (...)

(Anm: Evaluation of sleep, puberty and mental health in children with long-term melatonin treatment for chronic idiopathic childhood sleep onset insomnia. Psychopharmacology (Berl). 2011 Jul;216(1):111-20. Epub 2011 Feb 22.)

Diverse artikler

Antipsychotic Prescriptions in Iraq and Afghanistan Veterans With Posttraumatic Stress Disorder in Department of Veterans Affairs Healthcare, 2007–2012
J Clin Psychiatry 2015
Objective: Antipsychotic medications have been increasingly prescribed for off-label uses, including treatment of posttraumatic stress disorder (PTSD). Given limited knowledge about their use in returning Iraq and Afghanistan veterans with PTSD, we explored rates of antipsychotic use in this population and correlations with sociodemographic, military service, and psychiatric factors.

Method: Iraq and Afghanistan veterans with a PTSD diagnosis based on ICD-9-CM codes enrolled in Veterans Administration care between January 1, 2007, and September 30, 2011, were followed through September 30, 2012. Patients with a comorbid diagnosis of schizophrenia or bipolar disorder were excluded. Poisson regression models evaluated factors associated with prescriptions for antipsychotic versus other psychiatric medications (primary outcome).

Results: The mean age of our study population was 29.3 years, and 9.4% were women. Of 186,460 veterans with PTSD diagnoses examined, 19.9% received no psychiatric medications, and the remainder received psychiatric medications that excluded (61.2%) or included (18.9%) antipsychotics. In adjusted models, several factors were independently associated with antipsychotic use, including male sex (adjusted relative risk = 1.25; 95% CI, 1.20–1.30) and enlisted rank (1.44; 95% CI, 1.35–1.53). Increased likelihood of antipsychotic prescribing was associated with suicidal ideation (4.77; 95% CI, 4.59–4.95) and comorbid psychiatric diagnoses including personality disorder (4.27; 95% CI, 4.09–4.46), drug use disorder (3.56; 95% CI, 3.43–3.69), and alcohol use disorder (2.75; 95% CI, 2.65–2.84).

Conclusions: A substantial minority of Iraq and Afghanistan veterans diagnosed with PTSD received antipsychotics. Male veterans, those of enlisted rank, and those with suicidal ideation and psychiatric comorbidities were more likely to receive antipsychotics than other types of psychiatric medications. Providers should be cautious about antipsychotic use, given their known metabolic risks and questionable benefits for PTSD. (…)

Fortsatta skadestånd för Novartis
lakemedelsvarlden.se 2.6.2014
I Italien vill hälsoministeriet ha skadestånd för utebliven off label-förskrivning

För några månader sedan bötfällde konkurrensmyndigheten i Italien Roche och Novartis för otillåtet samarbete i syfte att skydda försäljningen av ögonläkemedlet Lucentis.

Nu vill även landets hälsovårdsdepartement ha ett skadestånd på 1,6 miljarder euro av de två företagen för att de haft ett övergripande avtal om att begränsa konkurrensen, rapporterar nyhetsbyrån Bloomberg. 
Det italienska hälsoministeriet säger att det begärda skadeståndet bygger på en uppskattning av vad Lucentis kostat landets sjukvårdssystem jämfört med om läkare förskrivit det billigare Avastin off label. (…)

U.S. high court leaves intact $142 million verdict against Pfizer
reuters.com 9.12.2013
(Reuters) - The U.S. Supreme Court on Monday left intact a $142 million jury verdict against Pfizer Inc over the company's marketing of the epilepsy drug Neurontin.

In 2010, a jury in Massachusetts found that due to Pfizer's marketing of the drug for off-label uses, Kaiser Foundation Health Plan Inc, one of the nation's largest health maintenance organizations, and affiliates were damaged because they paid for prescriptions relating to conditions Neurontin did not effectively treat.

The Supreme Court's refusal to hear Pfizer's appeal means similar claims brought against the company by insurer Aetna Inc and Harden Manufacturing Corp can also go forward. (...)

Novo Nordisk går med i lobbyfront i USA
medwatch.dk 15.10.2013
MEDICINAL & BIOTEK: Novo Nordisk vil sammen med andre medicinkæmper have lettere adgang til at informere om medicinens ikke-godkendte virkning. (...)

USA skærper advarsel på Novos store håb
business.dk 16.5.2013
De amerikanske myndigheder skriver nu for første gang, at der er observeret alvorlige tilfælde af betændelse i bugspytkirtlen hos patienter, som har fået Victoza. Men det er bare noget, de siger for at holde deres egen og industriens ryg fri, siger Novo-chef.

Novo Nordisks milliardsælgende diabetesmiddel Victoza har fået opdateret sin indlægsseddel i USA med informationer om, at der er observeret alvorlige tilfælde af betændelse i bugspytkirtlen hos patienter, som har fået Victoza.

Under sektionen "advarsler og forholdsregler" har de amerikanske myndigheder tilføjet følgende: "Baseret på spontane postmarketing rapporter, er akut pancreatitis (betændelse i bugspytkirtlen, red.), herunder fatal og ikke-fatal blødende eller vævsødelæggende pancreatitis, blevet observeret hos patienter behandlet med Victoza." (...)

I øjeblikket diskuteres det intensivt, om Victoza og de øvrige lægemidler rent faktisk er årsag til, at flere patienter end normalt får betændelse eller kræft i bugspytkirtlen. Det sker på baggrund af flere amerikanske studier og analyser, som antyder en sammenhæng; undersøgelser der dog ikke har involveret Victoza. Samtidig har amerikanske patienter indledt en række erstatningssager mod blandt andre Novo Nordisk, fordi de mener, at de har fået kræft i bugspytkirtlen efter at være behandlet med Victoza eller et af de andre lægemidler i klassen.

Novo Nordisk afviser pure enhver sammenhæng, lige som selskabet ikke mener, at der er noget af komme efter i retssagerne. Det sker med henvisning til, at selskabet ikke har set signaler på en sammenhæng i de mere end 1,2 millioner patient års behandling, som selskabet indtil nu har behandlet. (...)

(Anm: Victoza-sager om produktansvar afvises i USA. Medicinal & Biotek:   Novo Nordisk og en række andre medicinalselskaber har formået at få en stribe produktansvarssager afvist i USA. En dommer ved en føderal domstol har ifølge National Law Journal mandag afvist i alt 750 sager, der handlede om erstatning for kræft i bugspytkirtlen i forbindelse med brug af inkretinbaserede diabetesmidler, heriblandt Novos diabetesmedicin Victoza. (…) Men det skal siges, at sagsøgerne har en appelmulighed, så vi må lige se, om de vil benytte sig af den," siger kommunikationschef i Novo Nordisk Mike Rulis til Ritzau Finans. (medwatch.dk 13.11.2015).)

Små gnavere sætter kæp i Novo-hjulet
business.dk 3.4.2009
Der er gået mus og rotter i Novo Nordisks store satsning, Victoza. Øget forekomst af den sjældne c-cellekræft i skjoldbrugskirtlen hos mus og rotter i de dyreforsøg, som Novo Nordisk har foretaget med Victoza, ser ud til at sætte grus i Novos ellers velsmurte maskineri. (...)

Risiko for kræft
Betænkelighederne går først og fremmest på, om langtidsbrug af Victoza kan føre til kræft i skjoldbrugskirtlen. Ved dyreforsøg med mus og rotter har Novo Nordisks forskere nemlig fundet en øget forekomst af blandt andet såkaldt c-celle skjoldbrugskirtelkræft hos rotter og mus af såvel han- som hunkøn. Mens det ikke er så usædvanligt at finde denne type celleforandringer hos rotter, er det meget sjældent hos mus. (...)

Differences in Reporting of Analyses in Internal Company Documents Versus Published Trial Reports: Comparisons in Industry-Sponsored Trials in Off-Label Uses of Gabapentin
PLoS Med 2013;10(1):e1001378
Background Details about the type of analysis (e.g., intent to treat [ITT]) and definitions (i.e., criteria for including participants in the analysis) are necessary for interpreting a clinical trial's findings. Our objective was to compare the description of types of analyses and criteria for including participants in the publication (i.e., what was reported) with descriptions in the corresponding internal company documents (i.e., what was planned and what was done). Trials were for off-label uses of gabapentin sponsored by Pfizer and Parke-Davis, and documents were obtained through litigation. (...)

FDA Regulation of Off-label Drug Promotion Under Attack (FDA-regulering for promotering av legemidler off-label (forskrivning utenfor preparatomtale) angripes)
JAMA. 2013;309(5):445-446 (February 6, 2013)
References
In 2005, Alfred Caronia worked as a sales representative for the drugmaker Orphan Medical promoting the central nervous system depressant sodium oxybate (Xyrem),1 which had been approved by the US Food and Drug Administration (FDA) to treat narcolepsy. With the company's knowledge and approval,2 Caronia promoted the drug to physicians for numerous unapproved (“off-label”) indications—including insomnia and fibromyalgia—and claimed the drug was safe in elderly and pediatric patients, despite warnings on the label that safety was not established in those populations.

The Department of Justice investigated Caronia and Orphan Medical for violating the Food, Drug, and Cosmetic Act (FDCA). The manufacturer pleaded guilty, but Caronia did not. At trial, the government claimed that his representations to physicians effectively misbranded sodium oxybate because it was not FDA approved for the purposes he promoted. Caronia was convicted by a jury in 2008 and sentenced to probation, community service, and a $25 fine.

Caronia appealed the conviction, arguing that he had been prosecuted for his speech, breaching his First Amendment rights. The government responded that it had merely used his speech as evidence of his intent to misbrand the drug—that is, Caronia's statements showed he intended the drug to be used for purposes not described on the label. (...)

(Anm: Fibromyalgi: Fibromyalgi rammer over 100.000 norske kvinner. - En del tror sykdommen bare er tøys. Også blant leger er det en del som flirer av den, forteller professor. (…)   Når leger blir bedt om å rangere hvilke sykdommer det er mest prestisje å jobbe med, så havner alltid fibromyalgi nederst, forteller hun. Professor Egil Andreas Fors ved Institutt for samfunnsmedisin og allmennmedisinsk forskningsenhet ved NTNU er blant Norges fremste eksperter på sykdommen. Han bekrefter holdningene Slydal beskriver. (…) Sykdommen kjennetegnes gjerne ved at man har kroniske muskelsmerter, andre symptomer kan være utmattelse, hodepine, stivhet i kroppen, svimmelhet, kvalme, indre frost, depresjoner, angst og søvnproblemer. (kk.no 8.3.2016).)

(Anm: Lettere at diagnosticere fibromyalgi. På University of Colorado har forskere opdaget en speciel hjernesignatur, der med 93 pct. sikkerhed kan fastslå, hvorvidt en person lider af fibromyalgi eller ej. (pharmadanmark.anp.se 27.10.2016).)

Drug Marketing (Markedsføring av legemidler)
Off-label marketing: free speech or illegal promotion? (Off-label-markedsføring: ytringsfrihet eller ulovlig markedsføring?)
BMJ 2013;346:f320 (22 January)
The recent overturning of a conviction of a former sales representative for promoting off-label prescribing could mark a watershed for drug marketing in the US, Ed Silverman reports

When Alfred Caronia worked a decade ago as a sales representative for Orphan Medical—now part of Jazz Pharmaceuticals—he marketed sodium oxybate for cataplexy but also promoted the drug for other unapproved uses. In 2008 he was convicted of introducing a misbranded drug into interstate commerce for talking up unapproved uses. However, his conviction was overturned by a US appeals court panel last month after he successfully argued that his First Amendment rights were violated because the federal government failed to prove his remarks were false or misleading, potentially opening the doors for increased off-label marketing.
Off-label marketing is hardly new, of course. Physicians in the US are free to prescribe medications for uses not approved in product labeling, but the federal government has successfully reached settlements with dozens of drug makers for violating the Food, Drug and Cosmetic Act, which prevents them marketing a drug for unapproved uses. Recently, though, there has been some push back.

Several drug makers have filed lawsuits against the US Food and Drug Administration to argue that the agency is stifling commercial speech. Par Pharmaceutical, for instance, contended that its right to convey “truthful” information to physicians is protected by the First Amendment yet is thwarted by FDA regulation. The lawsuit is pending. (...)

How much freedom is healthy? (Hvor mye frihet er sunt?)
US editor’s choice
BMJ 2013;346:f514 (25 January)
The notion of personal liberty, particularly from government, is all pervasive in US culture. Currently, it is largely manifesting itself through the debate on gun control after the tragic events in Sandy Hook last month (www.nytimes.com/interactive/2012/12/14/nyregion/The-shooting-at-the-Sandy-Hook-Elementary.html).

Six months ago it featured high on the health agenda as the Supreme Court ruled on whether the individual mandate was a constitutionally allowable part of the Affordable Care Act (BMJ 2012;344:e2626; doi:10.1136/bmj.e2626).

And this week the theme was central to President Obama’s forthright inaugural address. In particular, in a speech in which individual freedom was very much to the fore, the president spoke about the tension this can have with central government: “Being true to our founding documents does not require us to agree on every contour of life. It does not mean we all define liberty in exactly the same way or follow the same precise path to happiness.

“Progress does not compel us to settle centuries’ long debates about the role of government for all time, but it does require us to act in our time” (www.washingtonpost.com/politics/president-obamas-second-inaugural-address-transcript/2013/01/21/f148d234-63d6-11e2-85f5-a8a9228e55e7_story.html). (...)

Off-label prescribing is common and indeed beneficial for some patients. Many physicians do it, and it is perfectly legal. Off-label marketing, however, is not, and the fines meted out to drug companies for this behavior have run into tens of billions of dollars over the years.

But a ruling last month could change all this. In 2008 a sales representative was convicted of introducing a misbranded drug into interstate commerce for talking up unapproved uses. His conviction was overturned by a US appeals court panel last month after he successfully argued that his First Amendment rights were violated because the federal government failed to prove his remarks were false or misleading.

The implications of this ruling for sales reps, industry, doctors, the Food and Drug Administration, and others are yet to be fully realized, but Ed Silverman’s feature takes the first footsteps into what could be a very different future as governance gives way to individual liberty (www.bmj.com/content/346/bmj.f320). (...)

Off-Label Marketing and the First Amendment
N Engl J Med 2013; 368:103-105 (January 10, 2013)
On December 3, 2012, a three-judge panel of a U.S. appeals court took a controversial leap toward what some fear will be license by the courts to invalidate a host of state and federal regulations, including some applicable to health care. In recent years, the Supreme Court has broadened the reach of the First Amendment, defining “protected speech” in such a way as to curtail or eliminate certain familiar governmental restraints. (See table for an overview of cases related to commercial speech and the pharmaceutical industry.) At issue in the December 3 opinion — which is doubtless headed for further appeal — were the Food and Drug Administration (FDA) regulations applicable to marketing of prescription pharmaceuticals for off-label uses. Overturning the conviction of a sales representative who was found to have engaged in off-label promotion of a prescription drug, a three-judge panel of the U.S. Court of Appeals for the Second Circuit (New York) held in United States v. Caronia that “the government cannot prosecute pharmaceutical manufacturers and their representatives under the [Food, Drug, and Cosmetic Act] for speech promoting the lawful, off-label use of an FDA-approved drug.”1 (...)

Pfizer to pay $55 million in drug misbranding case
pharmatimes.com 12.12.2012
By The Associated Press

The Justice Department says Pfizer Inc. will pay $55 million to resolve allegations that Wyeth LLC promoted the drug Protonix for uses that were not approved by the Food and Drug Administration. Pfizer acquired Wyeth in October 2009.

Wyeth obtained FDA approval to promote Protonix only for short-term treatment of erosive esophagitis. The condition is associated with gastro-esophageal reflux disease. Wyeth allegedly promoted Protonix for all forms of GERD from February 2000 to June 2001.

GERD is a condition in which food or liquid leak backwards from the stomach into the esophagus. (...)

- Eosinofil øsofagitt: oppdatering av behandling og kontroverser.

(Anm: Eosinophilic esophagitis: update on management and controversies. Abstract Eosinophilic esophagitis is a chronic allergen driven immune mediated disease that is increasingly recognized as a leading cause of dysphagia and foregut symptoms in children and adults. Much knowledge has been gained in recent years on the genetic and environmental risk factors for this disease, the associated inflammatory milieu, and the long term complications from esophageal remodeling. In this review we will highlight recent progress made in research into this disease, focusing on adults. (…) Incidence and prevalence The incidence and prevalence of eosinophilic esophagitis have risen over the past two decades.168910 In a report from Olmstead County, Minnesota, USA, no cases were documented before 1990, and the incidence rose from 0.35 cases/100 000 people to 9.5 cases/100 000 people over a 15 year period.6 Increased incidence has also been reported in Switzerland,5 the Netherlands,11 and Denmark.12 The reasons for this increase are poorly understood, and increased recognition is probably not the only cause.56 (…) Gut microbiome The human microbiome has been the subject of intense research interest in recent years; however, there is still a paucity of data on the microbiome of the esophagus. (…) Clinical presentation Adults and children with eosinophilic esophagitis have different clinical presentations.84858687 Children commonly present with difficulty feeding, vomiting, abdominal pain, or failure to thrive, whereas adults typically have symptoms of dysphagia, heartburn, chest pain, and food impactions.208488 This difference is thought to be, at least in part, related to gradual esophageal tissue remodeling arising from unabated inflammation.89909192 An inflammatory phenotype—endoscopic features including white exudates, linear furrows, and edema—is thought to eventually evolve as a result of longstanding inflammation into a fibrostenotic phenotype, with fibrotic features on endoscopy such as rings, strictures, and a narrow caliber esophagus.899394 BMJ 2017;359:j4482 (Published 13 November 2017).)

(Anm: Allergisk betennelse i spiserøret - eosinofil øsofagitt. Allergisk betennelse i spiserøret gir plager som ligner på syreplager, men symptomene forsvinner ikke med syrehemmende behandling (nhi.no 15.11.2017).)

Free speech rights outweigh restrictions on promoting drugs off label, court rules (Ytringsfrihetsrettigheter oppveier restriksjoner på å promotere legemidler off label, ifølge domstol)
BMJ 2012;345:e8324 (6 December 2012)
A federal appeals court in New York has ruled that regulations prohibiting the off-label promotion of prescription drugs are a violation of constitutionally protected free speech.1 The decision in the United States v Caronia case is likely to be appealed.

The drug at the center of the case is sodium oxybate (marketed in the US as Xyrem), which carries two label indications to treat conditions associated with narcolepsy. Data are insufficient to extend the label indication to children and elderly people, and it carries a “black box” warning of side effects.

A drug sales representative, Alfred Caronia, argued that regulations of the Food and Drug Administration limiting promotional activity only to the label indication of an approved drug were a violation of his rights to free speech under the First Amendment. He worked for Orphan Medical, the company that marketed sodium oxybate in the US, since acquired by Jazz Pharmaceuticals, and said that he should be allowed to promote off-label use as well. (...)

(Anm: Forskrivning utenfor preparatomtale ("off label") (utenfor indikasjon). (mintankesmie.no).)

Do Drug Reps Have Free-Speech Rights to Share Shoddy Studies? (Har legemiddelkonsulenter ytringsfrihet mht. å dele informasjon om juksestudier?)
slate.com 4.12.2012
I GSK-forliket deltok firmaet angivelig i forberedelsene, publisering og promotering i et tidsskrift som villedende hevdet at legemidlet Seroxat (Paxil) var effektivt til behandling av depresjon hos mindreårige. (In the GSK settlement, the company allegedly participated in preparing, publishing and promoting a journal article that misleadingly asserted its drug Paxil was effective in treating depression in minors.)

Legemiddelindustrien har påført den amerikanske regjeringen et dobbelt nederlag. US Court of Appeals i New York har avgjort at en legemiddelkonsulent har rett til å bruke sin ytringsfrihet til å promotere et narkolepsilegemiddel som effektivt mot søvnløshet, kronisk tretthet og andre tilstander som Food and Drug Administration ikke hadde godkjent. Dersom Høyesterett opprettholder denne beslutningen vil firmaene betale færre multi-milliard-dollar bøter og unyttige utgifter med økte helseutgifter. (Pharma has landed a double blow against the American government. The U.S. Court of Appeals in New York has ruled that a drug salesman was exercising his right to free speech by pitching a narcolepsy drug as effective against insomnia, chronic fatigue and other conditions the Food and Drug Administration had not approved. If the Supreme Court upholds this decision, companies will pay fewer multi-billion dollar fines and useless healthcare spending will increase.)

Tilsynsmyndighetene hevdet at promoteringen viste at selgerne ulovlig solgte et legemiddel. Men retten sa de hadde ytringsfrihet mht. å gi leger en sannferdig informasjon slik at de lovlig kunne foreskrive legemidlet. Tilsynsmyndighetene krenket denne retten ifølge dommerne ved å sperre for deres off-label anbefalinger. (Regulators argued that the pitch showed the salesman was illegally selling a misbranded drug. But the court said he had a free-speech right to give doctors truthful information so they could legally prescribe the medicine. The regulator violated that right, the judges ruled, by barring his off-label recommendations.)

Beslutningen gjelder kun i tre stater, men FDA vil trolig anke. Det vil kunne ta saken til Høyesterett og føre til at denne seieren for legemiddelindustrien setter nasjonal presedens. GlaxoSmithKline, for eksempel, måtte ut med 3 milliarder dollar i juli for å forlike tre tiltaler, to av dem for off-label-markedsføring av antidepressiva og andre legemidler. I de siste fire årene har Pfizer, Johnson & Johnson, Abbottand Eli Lilly hver betalt, eller i forhandlinger om å betale, forliket over 1 milliard dollar. (...) (The decision applies only in three states, but the FDA is likely to appeal. That could put the case before the Supreme Court and make this victory for the pharmaceutical industry a national precedent. GlaxoSmithKline, for instance, shelled out $3 billion in July to settle three indictments, two of which were off-label marketing of antidepressants and other drugs. In the past four years Pfizer, Johnson & Johnson, Abbottand Eli Lilly have each paid, or are negotiating to pay, settlements over $1 billion.)

Doctors, drug reps, and free speech
By: S. Y. Tan, MD, JD  Clinical Psychiatry News
Clinicalpsychiatrynews.com.com 10.2.2017
Question: The First Amendment guarantees the right of free speech, but the U.S. Supreme Court has held that under a strict scrutiny standard, the government may regulate: A. Obscenity. B. Fighting words. C. Professional speech. D. A and B. E. A, B, and C.

Answer: D. The First Amendment forbids the government from “abridging the freedom of speech,” which extends to certain nonverbal conduct, such as flag burning. At the same time, the U.S. Supreme Court has also ruled that certain categories of speech such as obscenity and fighting words can be regulated under a strict scrutiny standard. However, it remains unsettled whether and to what extent professional speech – such as in the context of the doctor-patient relationship – may be curtailed. (…)

(Anm: Er det en reproduserbarhetskrise i vitenskapelig forskning? (Is there a reproducibility crisis in science?) (…) Nyere studier, som undersøkte en rekke publiserte legemiddelstudier, klarte å gjenskape resultatene for mindre enn 25 % av dem - og tilsvarende resultater er blitt funnet i andre vitenskapelige disipliner. Hvordan bekjemper vi denne krisen for vitenskapelig ikke-reproduserbarhet? (ed.ted.com).)

(Anm: Spinn i randomiserte kontrollerte studier (RCT) på angstlegemidler (antidepressiva) med et positivt opprinnelig resultat: en sammenligning av bekymringer uttrykt av den amerikanske legemiddelkontrollen FDA og den publiserte litteratur. (Spin in RCTs of anxiety medication with a positive primary outcome: a comparison of concerns expressed by the US FDA and in the published literature.) BMJ Open. 2017 Mar 29;7(3):e012886.)

GlaxoSmithKline guilty of promoting blood drug for unlicensed use (GlaxoSmithKline skyldig i å fremme blod-legemiddel for ulisensiert bruk)
guardian.co.uk 7.11.2012
GSK sales representative found guilty of promoting Revolade for unlicensed use in serious breach of industry code of practice

GlaxoSmithKline was found not guilty of the more serious charge of reducing confidence in the pharmaceutical industry. Photograph: Alan Shoemake/Getty Images

A GlaxoSmithKline sales representative has been found guilty of promoting a medicine for an unlicensed use, just months after the drugmaker was fined a record $3bn for mis-selling drugs in the US.

GSK chief Sir Andrew Witty had vowed a company-wide overhaul would prevent a repeat of the mis-selling of the Paxil antidepressant for unlicensed use on children and other illegal practices.

But in another blow to the drug giant, a GSK employee has blown the whistle on a sales rep's promotion of the use of the Revolade blood disorder drug for myeloid fibrosis, a bone marrow disease for which it has no licence. The employee said a company salesperson had promoted the drug to an NHS consultant in an email. (...)

Fastholder tilstrekkelig off label-info
dagensit.no 1.11.2012
Statens legemiddelverk fastholder at de gir tilstrekkelig informasjon om utstrakt bruk av legemiddel utenfor godkjent indikasjon, såkalt off label-bruk.
Legemiddelindustrien, Legemiddelverket og legene har debattert heftig om utbredt off label-bruk.

Blant annet har adm. direktør Karita Bekkemellem i Legemiddelindustrien beskyldt Statens legemiddelverk for ikke å informere godt nok om mulig risiko ved å bruke Avastin for øyesykdommen våt AMD (aldersrelatert makuladegenerasjon).

Legemiddelet har ikke godkjent indikasjon for øyesykdommen, men brukes i stor utstrekning. Det finnes imidlertid et legemiddel med godkjent indikasjon, Lucentis. (...)

Ifølge medisinsk fagdirektør Steinar Madsen i Statens legemiddelverk mener Legemiddelverket at de gir tilstrekkelig informasjon om utstrakt bruk utenfor godkjent indikasjon. (...)

– I hvilken grad burde firmaet som har legemiddelet som brukes utenfor godkjent indikasjon informere om eventuell mulig risiko ved slik bruk?

– Dette er også et tema som har vært mye diskutert. Firmaene er bundet av at de ikke kan drive markedsføring utenom godkjent preparatomtale. Hvis en lege ringer til et legemiddelselskap og spør om fakta, har firmaet selvfølgelig anledning til å svare. Men det er en vanskelig avgrensningsproblematikk hvis det skulle åpnes for at et legemiddelfirma skal kunne informere om bruk utenom godkjent indikasjon - det blir lett markedsføring. Hovedprinsippet om at et firma ikke kan drive markedsføring utenom godkjent preparatomtale, mener vi er et viktig prinsipp. I dette tilfellet er det innført advarsler i preparatomtalen, og da kan firmaet bruke dette i sin markedsføring. (...)

Mener pasienter ikke informeres
dagensit.no 23.10.2012
Legemiddelselskapet Novartis mener norske pasienter ikke får god nok informasjon om utstrakt off label-bruk ved øyesykdom.

På Dagens Medisins nettside har adm. direktør Karita Bekkemellem Legemiddelindustrien, gått hardt ut mot Legemiddelverket og sykehusleger, som hun mener setter økonomiske hensyn foran pasientsikkerheten når de forskriver Avastin ved øyesykdommen aldersrelatert makuladegenerasjon (våt AMD).

OUS-leger tilbakeviser påstander om uforsvarlig behandling.

Avastin brukes utenfor godkjent preparatomtale, såkalt off label-bruk. Lucentis, som er godkjent for våt AMD, er langt mer kostbart og brukes i mindre grad. (...)

Skremme eller informere?
Karita Bekkemellem er leder av Legemiddelindustrien (LMI). Hun representerte Arbeiderpartiet fem perioder på Stortinget, og var statsråd i to regjeringer (2000-01 og 2005-07). Bekkemellem har vært leder av Aps kvinnebevegelse.
dagensmedisin.no 18.10.2012
Får norske pasienter informasjon om at de – i motsetning til pasienter i en rekke andre land – får medisin som ikke er godkjent for bruk for deres sykdom?

Mitt innlegg i Dagens Medisin om at norske sykehus bruker kreftmedisinen Avastin mot øyesykdommen våt AMD, har avstedkommet en kraftig reaksjon fra leger som mener denne praksisen er trygg og at jeg skremmer pasientene ved å påpeke økt risiko for bivirkninger.

Les også: OUS-leger tilbakeviser uforsvarlig behandling

Ordbruken er sterk, det hevdes at jeg forsøker å lure myndigheter og pasienter, og at jeg baserer meg på faktafeil. (...)

OUS-leger tilbakeviser uforsvarlig behandling
dagensmedisin.no 16.10.2012
Leger ved Oslo universitetssykehus avviser påstander fra Legemiddelindustrien om at behandling av pasienter med øyesykdom ikke er forsvarlig.

I et blogginnlegg på Dagens Medisin 11. oktober går leder av Legemiddelindustrien, Karita Bekkemellem, hardt ut mot Statens legemiddelverk og mener at Legemiddelverket setter økonomisk gevinst foran pasientsikkerhet når det gjelder behandling av øyesykdommen aldersrelatert makuladegenerasjon (våt AMD).

Stridens kjerne er behandling med to ulike legemidler: Avastin som ikke har godkjent indikasjon ved våt AMD, og Lucentis, som er godkjent for denne sykdommen.

I et debattinnlegg her på Dagens Medisin går nå leger ved Oslo universitetssykehus (OUS) hardt ut mot Bekkemellem og hevder av lederen av Legemiddelindustrien kommer med faktafeil og skremselspropaganda overfor pasientene. (...)

Skremsler og faktafeil fra LMI-direktøren
Olav Røise, professor og klinikkleder KKN ved Oslo Universitetssykehus (OUS), Ketil Eriksen, avdelingsleder ved Øyeavdelingen OUS, Ragnheidur Bragadottir, seksjonsoverlege ved netthinneseksjonen, Øyeavdelingen OUS, Karina Berg, vitenskapelig koordinator for LUCAS-studien
dagensmedisin.no 16.10.2012
Det er å håpe at myndigheter og pasienter ser Karita Bekkemellems forsøk på å lure oss. Det beste ville være om hun beklager innspillet slik at tilliten til LMI ikke settes på prøve.

I SIN BLOGG i Dagens Medisin på nett den 11. oktober henviser direktør Karita Bekkemellem i Legemiddelindustrien (LMI) til at Legemiddelverket i flere land i Europa advarer mot bruk av Avastin. Hun anklager det norske Legemiddelverket for å bidra til at pasienter som bruker Avastin, utsettes for stor risiko.

Legemiddelverket i Norge har, basert på de pågående studiene som sammenligner både effekt og bivirkninger ved de to medikamentene, avstått fra å komme med samme advarsel fordi dataene vi har i dag, klart viser at preparatene er likeverdige. (...)

Pasientsikkerhet er viktigere enn økonomisk gevinst
dagensmedisin.no 11.10.2012
Karita Bekkemellem er leder av Legemiddelindustrien (LMI). Hun representerte Arbeiderpartiet fem perioder på Stortinget, og var statsråd i to regjeringer (2000-01 og 2005-07). Bekkemellem har vært leder av Aps kvinnebevegelse.
Stadig flere land advarer mot bruk av medisiner på sykdommer de ikke er godkjent for. I Norge overser man risikoen for å spare penger.

Våt aldersrelatert makuladegenerasjon (våt AMD), eller forkalkning på netthinnen, er en øyesykdom som særlig rammer personer over 70 år. I dag finnes det en medisin – Lucentis – mot denne sykdommen. Imidlertid har norske sykehus valgt å bruke kreftmedisinen Avastin mot våt AMD uten at den er godkjent til slik bruk. (...)

Oklart ansvar för off label
lakemedelsvarlden.se 16.10.2012
Om verksamhetschefen beslutar om att ett inte godkänt läkemedel ska användas generellt, vem bär då ansvaret om en komplikation inträffar? Diskussionen om Avastin kontra Lucentis gör frågan aktuell.

När verksamhetschefen vid ögonkliniken i Lund aviserade att man i besparingssyfte skulle börja använda Avastin istället för Lucentis vid behandling av våt maculadegeneration vände sig en ögonläkare på kliniken till Socialstyrelsen för att få veta vem som har ansvaret om patienten får en komplikation vid injektionen.

– Det här är en mycket komplex fråga, säger Mathias Wallin jurist på enheten för regler och tillstånd.

I svaret skriver han att off label egentligen bara ska användas i undantag. Men om en vårdgivare tänker använda det på ett generellt plan så ”torde man” ha ett ansvar för att tidigt försäkra sig om att användandet är förenligt med god vård och för att ordinationerna följs upp.

Men även om det kommer ett beslut uppifrån måste en legitimerad yrkesutövare agera i överensstämmelse med vetenskapen och kunskapsläget när det gäller behandlingsformer, skriver Mathias Wallin i sitt svar.

– Det här är ett illustrativt exempel på en brännande frågeställning, säger Bengt Ljungberg vetenskaplig rådgivare på Läkemedelsverket. (...)

Marketing of antipsychotic drugs targeted doctors of Medicaid patients, report says (Markedsføring av antipsykotiske legemidler rettet mot leger til Medicaid-pasienter, ifølge rapport)
BMJ 2012;345:e6633 (2 October 2012)
Psychiatrists serving the 205 000 low income people covered by the Medicaid program in Washington, DC, disproportionately benefited from gifts and payments from pharmaceutical companies, compared with other local physicians, a study shows.

In addition, children covered by Medicaid, a principal focus of the program, were twice as likely as all Americans to be prescribed antipsychotic drugs. About one child in 10 was prescribed that class of drugs.

Those two associations were gleaned from an analysis of marketing data that pharmaceutical companies reported to the government of the District of Columbia under the AccessRx Act, which was passed in 2004. The George Washington University School of Public Health and Health Services conducted the analysis under a contract from the city, and has published it on the district’s website.1

The law requires companies to report expenditures greater than $25 (£15.5; €19.3) for meals, speaking, and consulting fees, and so on. Spending on research, congressional lobbying, and drug samples are excluded. The law covers all health professionals, not just doctors, and all institutional settings.

Pharmaceutical marketing costs totalled $85.4 million in 2010, when the city’s population was barely over 600 000. Direct payments were made to 172 physicians, totalling $1.9 million, Susan Wood, senior author of the paper, told the BMJ.

About a quarter of that amount, nearly $500 000, went to only 26 psychiatrists. Psychiatrists with patients covered by Medicaid received a greater share of the largesse than those who do not treat Medicaid patients.

“We found a disturbing number of people dependent upon Medicaid who are being prescribed antipsychotic medication,” Wood said. “It shows there is a real effort on the part of manufacturers to disproportionately market antipsychotic drugs to clinicians” who are serving a Medicaid population.

Problematic side effects associated with second generation antipsychotic drugs—those most likely to still be on patent and hence promoted—include sedation, weight gain, diabetes, and metabolic syndrome. A risk-benefit assessment that might be acceptable for serious conditions for which the drug was approved might not be acceptable for off-label use for less serious conditions. (...)

(Anm: Impacts of Pharmaceutical Marketing on Healthcare Services in the District of Columbia: Focus on Use of Antipsychotics in Children. 2012. (doh.dc.gov 20.9.2012).)

Departementet vedgår svakheter
dagensmedisin.no 21.6.2012
Helse- og omsorgsdepartementet (HOD) innrømmer at ulike finansieringsordninger kan bidra til forskrivingsvridning.

- De ulike finansieringsordningene kan i visse tilfeller føre til en risiko for uønsket forskrivingsvridning og forskyving av kostnader, sier statssekretær Ragnhild Mathisen i HOD til Dagens Medisin.

Hun legger til at disse utfordringene var bakgrunnen for at det i 2006 ble gjennomført en endring i finansieringsansvaret for visse legemidler. Da fikk helseforetakene ansvaret for å finansiere legemidler som brukes utenfor institusjon, eksempelvis TNF-hemmere. (…)

Europe patient group demands action on off-label safety
pharmatimes.com 11.5.2012
As the debate over off-label use is reignited following the publication of data on Roche's cancer blockbuster Avastin as a treatment for wet age-related macular degeneration, the European Alliance for Access to Safe Medicines is calling for urgent action to clarify when drugs can be used outside their approved status.

The patient group's concerns follow the publication a week ago of data from the two-year CATT study funded by the US government which revealed that Avastin (bevacizumab) and Roche/Novartis' eye drug Lucentis (ranibizumab) are equivalent in treating wet AMD, though the former is not approved for that indication. That was followed by a second, UK-based study, called IVAN, which also found that the drugs were comparably effective and claimed that the National Health Service could save more than £84 million per year if Avastin was used instead of Lucentis.

However, the EAASM notes comments from the chief executive of the UK's Macular Disease Society, Helen Jackman who welcomed the studies but noted that "they cannot provide definitive safety information and the overall question of the safety of Avastin is, unfortunately, not answered to everyone's satisfaction by these trials". She adds that the use of Avastin "will remain a matter of judgement for clinicians, with some satisfied with the evidence and others not". (...)

Studie viser stor off-label brug af lægemidler
euroinvestor.dk 23.4.2012
Et canadisk studie viser nu, at såkaldt "off-label" brug, hvor lægemidler udskrives til behandling af andre sygdomme, end de er godkendt til, er ret så udbredt fænomen. Et studie fra den canadiske provins Quebec viser, ifølge Reuters, at 11 pct. af recepterne kunne klassificeres som off-label.

Studiet bygger på 250.000 recepter udskrevet i perioden 2005-2010 til lige over 50.000 patienter af 113 praktiserende læger.

Medicinalselskaberne må ifølge loven ikke markedsføre medicin til områder, det ikke er godkendt til. Lægerne bliver dog ofte opmærksomme på mulighederne i forbindelse med studier af medicinen til anden anvendelse. Eksempelvis bruges Novos diabetes 2-middel, Victoza, ifølge analytikere allerede off-label til fedmebehandling. Novo er i færd med de afsluttende kliniske fase 3-studier af Victoza til behandling af fedme og håber at kunne lancere Victoza som vægttabsmedicin i 2014. (...)

Study finds high rates of off-label prescribing
reuters.com 19.4.2012
(Reuters Health) - More than 10 percent of prescriptions in one Canadian province were for drugs not approved to treat the patient's condition, a new study finds. And many times, there was little evidence the drugs would work.

A medication is being used "off label" if a doctor prescribes it to treat a condition other than the one(s) Health Canada, the U.S. Food and Drug Administration or similar national regulatory agencies approved it for based on tests of safety and efficacy.

Dr. Tewodros Eguale, who led the new study, said doctors typically prescribe medications off-label when their patients fail to respond to other popular approved drugs or when they have a rare condition with few available treatments.

Eguale, from McGill University in Montreal, and his colleagues used data on every prescription written by Quebec physicians participating in an electronic health record network. The network is unusual in that it requires a doctor to state what the prescribed drug is intended to treat.

Between 2005 and 2010, 113 primary care doctors wrote more than 250,000 prescriptions for just over 50,000 patients.

Eleven percent of those prescriptions were considered off-label by the standards of the Health Canada drug database. (...)

(Anm: Drug, Patient, and Physician Characteristics Associated With Off-label Prescribing in Primary Care. Arch Intern Med. 2012 (Published online April 16).)

Psychotropic prescribing in Catalonia: results from an epidemiological study
Family Practice (2012) 29 (2): 154-162 (April)
(...) Background. Mental disorders (MDs) are mainly treated in primary care (PC), where psychotropic drug (PSD) prescribing is highly prevalent. Prescription of PSD is associated with clinical and non-clinical factors.

Purpose. To describe the patterns of PSD prescribing over a 12-month period and to determine the factors associated with this in a PC population.

Methods. Cross-sectional study. Data were collected on 3815 patients, via patient interview, on sociodemographics and MDs [Diagnostic and Statistical Manual of Mental Disorders (DSM-IV criteria)]. Computerized records provided data on PSD prescribing. Multilevel logistic regressions assessed the factors that influence prescribing.

Results. Thirty-four per cent of PC patients were prescribed PSDs >12 months, with anxiolytics being the most commonly prescribed (22%). Fifty-three per cent of patients with any MD in this 12-month period were prescribed PSDs; however, 25% of patients without any of these disorders were also prescribed these medications. Higher rates of prescribing were associated with female gender, older age, presence of MD, being a househusband/housewife, consulting about psychological problems, increasing number of consultations and higher self-perceived disability. PSDs were less likely to be prescribed to patients born outside Spain and those consulting about physical conditions. PSD prescribing was higher in patients previously married and antipsychotic prescribing was higher in patients never married. No statistically significant associations were found between PSD prescription and education.

Conclusions. PSD prescribing rates are high in Catalonia and are associated with a number of clinical and non-clinical factors. A significant proportion of patients are receiving these drugs in the absence of MD. These findings need to be considered when prescribing in PC. (...)

Speeding up access to new drugs (Raskere tilgang til nye legemidler)
BMJ 2012;344:e999 (17 February)
Plans to cut the time it takes to get innovative treatments into clinical practice are finally to be put out to consultation next month. Nigel Hawkes provides a reminder of the key points

The prime minister promised at the end of last year to give some patients quicker access to new drugs. Was this just an empty aspiration?

No. A lot of thought has been given to a faster access scheme since David Cooksey recommended it in his review of UK health research funding in December 2006. A working group from industry and government produced a plan by November 2009. It sat on a shelf until resurrected two years later.

How would it work?
Medicines that have completed phase III trials (or in exceptional circumstances phase II) and that will treat or prevent life threatening, chronic, or seriously debilitating conditions that lack adequate existing treatments would qualify. Manufacturers would have to apply, and a decision would be promised in 75 days.

How would that be any quicker than licensing, if phase III trials have already been completed?
It usually takes a year or more to get licensing approval after a successful phase III trial. The new process is expected to get these medicines to patients a year earlier than otherwise would be the case.

But doesn’t it mean that proper risk assessment will be skimped?
There’s a danger of that. The burden of risk will be shifted towards the doctor and the patient and away from the manufacturer. Good information will be vital; patients will need to be fully informed and give active consent. Legally, the position will be the same as that for any unlicensed medicine, and the working group believes—but cannot guarantee—that primary care trusts or clinical commissioning groups will not be liable should anything go wrong. And it says that if the decision by a doctor to treat a patient was reasonable in all the circumstances and all relevant information was provided, a successful claim for negligence is unlikely.

If unlicensed medicines can be marketed and sold, what’s the point of licensing?
The medicines under this scheme would be exceptional and few in number, perhaps only one or two a year. The NHS already uses unlicensed or off-label medicines in some cases, on the authority of the prescribing doctor (for example, bevacizumab for age related macular degeneration). Patients consulted by the working group were confident that they were competent to make a proper assessment of the risks. Doctors were not so sure. (...)

Evidence and desperation in off-label prescribing: recombinant factor VIIa
BMJ 2012;344:d7926 (16 January)
Wendy Lipworth and colleagues explore why clinicians prescribe recombinant factor VIIa off-label for major haemorrhage, despite a lack of supporting evidence—and why this matters

Off label prescribing—that is, prescribing a medicine for an indication not listed in the product information, or for a patient outside the approved age range—is common, but controversial. On the one hand, it can promote clinical innovation and provide options for patients for whom no other alternatives are available. On the other hand, it can be harmful, because safety data are often lacking; it impedes the generation of good quality evidence, and it comes at a considerable cost to patients, governments, and other payers.1 2 (...)

Høyt spill med pasienter
farmatid.no 22.11.2010
Bruken av legemidler utenfor godkjent indikasjon i Norge er omfattende, uoversiktlig og full av dilemma. — Vi ønsker ikke off label-bruk, sier overlege Steinar Madsen i Legemiddelverket.

I finanskrisetider og med en stadig aldrende befolkning ser også helsemyndigheter etter måter å spare penger på. Blant annet ved å gi pasienter legemidler utenfor godkjent indikasjon. Norske leger og helseforetak er villige til å ta sjanser på pasienters vegne, og det for en budsjettpost, legemidler, som kun utgjør vel ti prosent av det totale helsebudsjettet. Bruken av såkalte off label- og off licence-legemidler i Norge har pågått i årevis og i betydelig omfang, ifølge leger Norsk Farmaceutisk Tidsskrift har snakket med. Pasientrisikoen er høy. Rapportering skjer unntaksvis. Praksisen er løs, uoversiktlig og full av dilemma. (...)

Å tøyle et problembarn
farmatid.no 22.11.2010
Legemidler som benyttes utenfor godkjent indikasjon skaper hodebry. På den ene siden kan bruken av såkalt off label-medisin være grensesprengende i oppdagelsen av nye bruksområder, på den annen side det rene lotteri med fatal utgang. At økonomi spiller en sentral rolle, er en ytterligere kompliserende faktor. Det er ikke til å undres over at mange har et elsk/hat-forhold til problembarnet. (...)

Ansvar og oppfølging ved bruk av legemidler utenfor godkjent indikasjon
kvalitetogprioritering.no 11.4.2011
Bruk av legemidler utenfor godkjent indikasjon, ”off-label” bruk, omfatter forskrivning av registrerte legemidler utenfor godkjent bruksområde. Nasjonalt råd for kvalitet og prioritering i helsetjenesten har tidligere behandlet en sak som berører denne problemstillingen: ”Innføring av ny og kostbar teknologi - Lucentis vs. Avastin”. Hvordan kan eller bør den norske helsetjenesten håndtere off-label bruk av legemidler? (...)

Author Insights: Off-Label Use of Antipsychotics Helpful for Only a Few Conditions (Forfatters innsikt: Forskrivning av atypiske antipsykotika utenfor preparatomtale hjelper bare mot noen få tilstander)
JAMA 2011 (September 27)
While off-label use of atypical antipsychotics has skyrocketed in recent years, such treatment is beneficial for only a handful of conditions, an analysis published today in JAMA found.

The US Food and Drug Administration has approved the use of atypical antipsychotic medications to treat adult patients with schizophrenia and bipolar disorder. Certain antipsychotics have also been approved for treating a subset of patients with depression. However, US physicians are also allowed to use drugs “off label” to treat other conditions. A doubling of such off-label use of atypical antipsychotics is a driving force behind an increase in medication visits related to these drugs, from 6.2 million visits in 1995 to 14.3 million in 2008.

These trends have raised concerns among some clinicians because this class of drugs is associated with serious adverse events that include substantial weight gain, movement disorders, and even death. (...)

(Anm: Importance of Early Weight Changes to Predict Long-Term Weight Gain During Psychotropic Drug Treatment. Background: Psychotropic drugs can induce substantial weight gain, particularly during the first 6 months of treatment. (…) Results: Prevalences of metabolic syndrome and obesity were 22% and 17%, respectively, at baseline and 32% and 24% after 1 year. (…) Conclusion: Following prescription of weight gain–inducing psychotropic drugs, a 5% threshold for weight gain after 1 month should raise clinician concerns about weight-controlling strategies. (J Clin Psychiatry 2015;76(11):e1417–e1423).)

(Anm: Metabolic Syndrome Components Are Associated With Symptomatic Polyneuropathy Independent of Glycemic Status. Diabetes Care 2016 (March 10, 2016).)

(Anm: New cause of immune neuropathy discovered. Hope for a better diagnosis. "Our study backs the assumption from previous studies that patients who have antibodies against proteins of Nodes of Ranvier exhibit characteristic features," says Kathrin Doppler. This means: The disease develops rapidly, causes severe paralysis and responds poorly to standard therapy with corticosteroids or immunoglobulins but excellently to Rituximab treatment. The Würzburg neurologists found that strong neuralgia is another typical symptom in patients with Caspr antibodies. Patients with antibodies against the two other proteins, Neurofascin-155 and Contactin-1, in contrast typically exhibit a distinct tremor in targeted movements. (medicalnewstoday.com 9.8.2016).)

(Anm: Auto-antibodies to contactin-associated protein 1 (Caspr) in two patients with painful inflammatory neuropathy. Brain. 2016 Jul 29. pii: aww189. [Epub ahead of print].)

(Anm: Prepsychosis links with elevated metabolic syndrome. MADRID – Untreated people at high risk for developing psychosis also showed an increased prevalence of certain components of metabolic syndrome in data collected from 163 German study participants, a finding that gives new insight into the well-documented but poorly delineated link between schizophrenia and metabolic syndrome. (...) He also suggested prescribing antipsychotic medications that pose the lowest risk for causing further metabolic derangements in patients. (clinicalpsychiatrynews.com.com 2.4.2016).)

(Anm: Joachim Raese, MD. Metabolic syndrome is defined by the aggregation of hypertriglyceridemia, low high-density lipoprotein (HDL) levels, elevated fasting glucose, hypertension, and increased waist circumference. Metabolic syndrome confers an increased risk of developing diabetes and of dying from coronary artery disease. Cardiovascular disease is the leading cause of death among patients with schizophrenia, who have a life expectancy about 20 years shorter than the general population. (…) For a more detailed discussion, I suggest watching a YouTube video that we have prepared. (cmeinstitute.com 27.4.2016).)

(Anm: Video Lecture 8: Metabolic Syndrome Lectures 1 (By Dr. Joachim Raese) (youtube.com).)

(Anm: Women with type 2 diabetes at greater cardiovascular risk than men. While it is well established that individuals with diabetes are at higher risk for cardiovascular disease, a new scientific statement from the American Heart Association claims this risk may be significantly greater for women with the condition. Published in the journal Circulation, the statement also says women with type 2 diabetes may need to take more action than men to lower their risk for heart attack and stroke. (medicalnewstoday.com 8.12.2015).)

(Anm: Type 2 diabetes: blood pressure drugs may be harmful for some patients. For some patients with type 2 diabetes, treatment with intense blood-lowering medication may do more harm than good. This is according to a new study published in The BMJ. (medicalnewstoday.com 26.2.2016).)

(Anm: Sex Differences in the Cardiovascular Consequences of Diabetes Mellitus: A Scientific Statement From the American Heart Association. Circulation. 2015; 132(25): 2424-47.)

(Anm: Efficacy and Comparative Effectiveness of Atypical Antipsychotic Medications for Off-Label Uses in Adults. JAMA. 2011;306(12):1359-1369 (September 28).)

Novo Nordisk anklaget for bestikkelse
bt.dk 25.9.2011
Læge står frem: Fik hotelophold, restaurantbesøg og penge

Militærlæge Ian Black fortæller om bestikkelse fra Novo Nordisk.

Novo Nordisk er anklaget for at have bestukket læger i det amerikanske militær til at bruge et medicin mod blødninger. Men medicinen har ikke en dokumenteret virkning.

Nu står en af lægerne frem i 21 Søndag på DR 1. Den amerikanske militærlæge Ian Black brugte medicinen til sårede amerikanske soldater, men han fandt ud af, at det ikke virkede. Militærlægen oplevede alvorlige bivirkninger, når han brugte det på amerikanske soldater.

- Jeg oplevede hjerteanfald, slagtilfælde og mærkelige blodpropper i indvoldene, fortæller Ian Black i 21 Søndag på DR 1.

Ifølge DR’s indslag i aftes viste en undersøgelse i 2005, at næsten 10 pct. af de, der blev behandlet med NovoSeven, fik blodpropper. Dermed blev Ian Blacks observationer bekræftet.

Alvorlige bivirkninger
Den påstand bakkes op af Steffen Thirstrup, som er leder af Lægemiddelstyrelsen i Danmark. Ifølge Lægemiddelstyrelsen er der ingen dokumentation for virkningen af medicinen.

- Lægemidlet bliver brugt til patienter, der ikke har gavn af det. De har på bundlinjen kun risiko for blodpropper, siger han til 21 Søndag. Lægemiddelstyrelsen kritiserer Novo Nordisk for at have tjent millioner kroner på medicinen, uden at der er blevet lavet kliniske studier, der viser, om den virker.

- Der er tale om medicin med de alvorligste bivirkninger, nemlig at man kan få blodpropper og dø af det, siger Steffen Thirstrup.

Efter indslaget fortalte Kim Bildsøe Lassen, at Novo Nordisk havde solgt for 1,2 mia. kr off-label, altså til formål, der ikke er godkendt.

Sag mod Novo Nordisk
Da Ian Black opdagede bivirkningerne gik han til myndighederne, og det amerikanske justitsministerium lagde sag an mod Novo Nordisk.

Militærlægen var kronvidne og whistleblower i sagen. Det var altså ham, der fortalte ministeriet om de alvorlige følger af NovoSeven, og om at Novo Nordisk havde bestukket ham og andre læger.

- Jeg blev tilbudt ubegrænsede penge til uddannelse, gode middage på dyre restauranter og firestjernede hotelophold, siger Ian Black.

Men sagen kom aldrig i retten, og i stedet invilligede Novo Nordisk i at betale 25 mio. dollars - ca. 130 mio. kr - i et forlig. Ian Black mener, at det forlig har været en god forretning for Novo Nordisk.

- 25 mio. dollars er mange penge, men sammenlignet med de mange mio., de har tjent, så er det ikke ret meget, siger han til 21 Søndag. (...)

Flera blinda i USA efter behandling med Avastin
lakemedelsvarlden.se 2.9.2011
Flera personer i USA har blivit blinda och andra har drabbats av svåra infektioner efter att ha behandlats med Avastin, som används mot våt makuladegeneration.

Minst tolv personer i Miami-området i USA har fått allvarliga ögoninfektioner på grund av streptokocker efter att ha behandlats med Avastin, skriver Reuters. Alla patienter hade dålig syn före behandlingen, men många förlorade synen helt efteråt. Tidningen New York Times uppger att fem personer blivit blinda i Los Angeles efter Avastin-injektioner.

FDA har härlett smittan till ett apotek i Florida. Man avråder inte från injektioner, men uppmanar behandlare att vara uppmärksamma på smittorisken.

Avastin (bevacizumab) är ett cancerläkemedel, men eftersom det är mycket billigare än till exempel Lucentis (ranibizumab) används det för att behandla åldersrelaterad makuladegeneration. Lucentis kommer i engångsförpackningar medan Avastindosen måste fördelas. Det är vid omfördelningen av doser som läkemedlet kontaminerats. (...)

Off-label Avastin use linked to eye infections (Forskrivning av Avastin utenfor preparatomtale linket til øyeinfeksjoner)
pharmatimes.com 1.9.2011
The US Food and Drug Administration is looking into cases of serious eye infections in patients who have been treated with Avastin, Roche's blockbuster which is often prescribed off-label to treat wet age-related macular degeneration.

The agency is alerting healthcare professionals that repackaged intravitreal injections of Avastin (bevacizumab) "have caused a cluster of serious eye infections" in Miami, and investigators traced the tainted injections to a single pharmacy. The latter then distributed the Avastin to multiple eye clinics.

To date, FDA is aware of at least 12 patients in at least three of these clinics who had Streptococcus endophthalmitis eye infection. While all of them "had visual deficits prior to their injections with Avastin, some of these patients lost all remaining vision in that eye due to the endophthalmitis", the agency said. There have also been reports of four patients in Tennessee who were injected with Avastin that was supposedly contaminated by bacteria. (...)

Novo Nordisk anklages for at smøre militærlæger
business.dk 23.8.2011
Den amerikanske hær begyndte i 2004 at bruge NovoSeven som standardbehandling til sårede amerikanske soldater i Irak.

Millionforlig i sag, hvor Novo Nordisk mistænkes for at give limousinetransport og dyre middage til militærlæger, hvidvaskning af bestikkelse til lægerne og ulovlig betaling for forsøg med sårede soldater i Irak og Afghanistan.

Det er ikke småting, Novo Nordisk beskyldes for at stå bag, når man læser søgsmålet om ulovlig markedsføring af blødermedicinen NovoSeven, som det amerikanske justitsministerium sammen med 24 delstater og to såkaldte whistleblowers afleverede for snart to år siden.

Søgsmålet, som først nu er kommet til offentlighedens kendskab, resulterede i juni i år i, at Novo Nordisk indgik et 130 millioner kroner stort forlig, uden at den danske medicinalkoncern erkender skyld. Novo Nordisks ledelse fastholder, at selskabet ikke har gjort noget forkert.

Søgsmålet tegner billedet af en virksomhed, hvis sælgere har været villige til at gå langt for at leve op til de store krav, som blev stillet til dem fra virksomhedens side. I anklageskriftet konstateres det, at Novo Nordisk på systematisk vis forsøgte at få udbredt brugen af NovoSeven til behandling af traumepatienter, selv om midlet ikke var godkendt til formålet. (...)

Bad Side-Effects Ahead For Pharma?
blogs.forbes.com 30.6.2011
In 2006, according to The New York Review of Books, four-year-old Rebecca Riley died of the effects of two prescription drugs—Clonidine and Depakote.

These medications, along with Seroquel, were prescribed for Rebecca after she was diagnosed, at the age of two, with attention deficit hyperactivity disorder (ADHD) and bipolar disorder. The three drugs are not approved by the Food and Drug Administration (FDA) for treatment of ADHD or long-term treatment of bipolar disorder, nor are they approved for children as young as Rebecca.

The New York Review of Books’ recent two-part article (1) by Marcia Angell on the treatment of mental illness with psychoactive drugs (those that affect the mental state) addresses an issue that may one day prove very important to investors in pharmaceutical stocks. (All statistics and quotations herein are drawn from Dr. Angell’s article.)

It is not illegal for a doctor to prescribe a drug off-label, that is, for a non-FDA-approved use, but a drug marketer cannot lawfully encourage a doctor to do so. The profits in psychoactive drugs, however, make it tempting to flout the law. In the past four years, AstraZeneca (AZN), Pfizer (PFE), Eli Lilly (LLY), Bristol-Myers Squibb (BMY) and Forest Labs (FRX) have all settled federal charges of marketing psychoactive drugs off-label, at a cost running into hundreds of millions.

Seeing that pharmaceutical marketing executives are evidently undeterred by the law, Dr. Angell, a senior lecturer in social medicine at Harvard Medical School and former editor in chief of The New England Journal of Medicine, advocates a prohibition on prescribing psychoactive drugs off-label.

A ban would cut into a major growth area for pharmaceutical companies. (...)

Crossing the Line: The Trial of GlaxoSmithKline Lawyer Lauren Stevens
law.com 23.6.2011
When the U.S. Department of Justice charged former in-house lawyer Lauren Stevens with six felonies, it aimed to send a clear message that no one should lie to federal investigators—including lawyers. But the short and bitter trial that followed backfired. In the end it conveyed a message to both in-house counsel and prosecutors about the dangers of overzealousness.

On May 10, in a move that was as sudden as it was dramatic, a federal district court judge in midtrial acquitted the former in-house counsel at GlaxoSmithKline of all six counts. While Stevens and her lawyers celebrated with champagne, sources say the stunned prosecutors privately complained that the jury would have found Stevens guilty had the judge let the trial continue. (...)

Ex-Glaxo Lawyer `Went Too Far,’ U.S Says at Opening of Obstruction Trial
bloomberg.com 27.4.2011
An ex-GlaxoSmithKline Plc (GSK) attorney accused of covering up the company’s improper marketing of its antidepressant drug Wellbutrin SR is a “lawyer who went too far,” a federal prosecutor said as her trial began.

Lauren Stevens, former vice president and associate general counsel for London-based Glaxo, is charged with impeding an inquiry in 2002 and 2003 by the U.S. Food and Drug Administration into the marketing of the drug for uses not approved by the FDA.

“This is a case about a lawyer who put loyalty to her company above fidelity to the truth and to the law,” said Patrick Jasperse, a Justice Department lawyer, during opening statements today in Greenbelt, Maryland, federal court. “This is a case about a lawyer who went too far, from aggressively representing her company to breaking the law.” (...)

Off-label drug use: report warns of dangers for patients
pharmatimes.com 19.4.2011
A new report warns of "very serious consequences" for patient safety when health care decisions are made not in the best interests of the patient but as a result of cost-cutting allowed by "regulatory vagaries and loopholes."

The study, published by the European Alliance for Access to Safe Medicines (EAASM), warns of the dangers to the public posed by the use of unlicensed medicines, questionable off-label use of drugs and the recycling and re-use of licensed single-use medical devices.

A case study included in the report examines the use of two drugs used in the treatment of wet age-related macular degeneration (AMD), one of the major causes of visual impairment and blindness in adults aged over 50 in the developed world.

Only one of the drugs has been licensed by the European Medicines Agency (EMA) for use in the treatment of eye diseases, yet the other is widely used off-label and this, says the report, has given rise to "horrifying adverse reactions in patients, for example complete loss of vision."

There are also indications of other safety issues, such as a potential increase in stroke with use of the unlicensed product compared to the licensed therapy, it adds. (...)

Off-label, unauthorised Rxing in children “widespread” in Europe
pharmatimes.com 27.1.2011
The prescribing of off-label and unauthorised medicines to children is still widespread in Europe, accounting for 45%-60% of total prescriptions in both inpatient and outpatient care, says a new report from the European Medicines Agency (EMA).

The study findings show the highest rates of use are in very young children and in children with very severe conditions. It also notes that the therapeutic classes that are used most frequently off-label or without a marketing authorisation are: antiarrhythmics, antihypertensives (renin-angiotensin inhibitors and beta-blockers) proton pump inhibitors and H2-receptor antagonists, antiasthmatics, and antidepressants (mainly selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors and tricyclic antidepressants), contraceptives (in adolescents), and antibiotics (in very young children). (...)

Alvorlige bivirkninger etter ikke- godkjent (”off-label”) bruk av Vistide
legemiddelverket.no 26.1.2011
Det er rapportert om bivirkninger etter bruk av Vistide ved ikke-godkjente bruksområder og/eller administrasjonsveier.

Vistide (cidofovir) er godkjent for behandling av cytomegalovirus-retinitt hos voksne med AIDS, og skal gis som intravenøs infusjon. Vistide har markedsføringstillatelse i Norge, men er bare tilgjengelig via produsenten.

Bivirkninger
De hyppigste og mest alvorlige rapporterte bivirkningene er nyretoksisitet, okulær toksisitet og nøytropeni.

Det er også rapportert bivirkninger i tilfeller der Vistide er brukt utblandet i salve eller krem. Rapportene antyder at slik lokal bruk (reformulert som krem eller salve), ikke forhindrer at pasienten opplever systemisk toksisitet. Bivirkninger rapportert etter lokal bruk var rødhet i huden, smertefulle sår og nyreskade.

Det er også sett manglende effekt i tilfeller der Vistide er brukt utenfor godkjent bruksområde. Manglende effekt hadde i enkelte tilfeller fatalt utfall. (...)

Atypicals Increasingly Used Off-Label (Økende forskrivning av atypiske utenfor preparatomtale)
medpagetoday.com 9.1.2011
Atypical antipsychotic use continues to grow, and in recent years these costly drugs were increasingly prescribed for off-label indications -- sometimes without convincing evidence to support that use, researchers reported.

An analysis of a nationally representative sample of physician office visits involving atypical antipsychotics found that use of the drugs increased overall from 6.2 million (95% CI 5.4 to 7) in 1995 to 16.7 million (95% CI 15.5 to 18.2) in 2006, according to Caleb Alexander, MD, of the University of Chicago, and colleagues.

During the 15-year period analyzed, patient visits for typical antipsychotics decreased from 5.2 million (95% CI 4.5 to 5.9) to 1 million (95% CI 0.8 to 1.3) -- while visits for atypical agents skyrocketed from 1 million (95% CI 0.8 to 1.2) to 13.3 million (95% CI 12 to 14.5) by 2008, Alexander's group reported online in Pharmacoepidemiology and Drug Safety. (...)

(Anm: Increasing off-label use of antipsychotic medications in the United States, 1995–2008. Pharmacoepidemiology and Drug Safety 2010 (Article first published online: 6 JAN 2011).)

GSK lawyer is indicted on charges of obstructing FDA proceeding (GSK-advokat siktet etter anklager om å forhindre FDA-prosedyre)
BMJ 2010; 341:c6570 (17 November)
The US Department of Justice has charged Lauren Stevens, a retired GlaxoSmithKline (GSK) lawyer, in relation to alleged off-label marketing of a drug. She faces one count of obstructing an official proceeding, one count of concealing and falsifying documents to influence a federal agency, and four counts of making false statements to the Food and Drug Administration.

Although drug companies have in the past been charged with off-label marketing of drugs, and several have paid large fines, it is thought that this is the first time an individual has been charged. GSK has not been charged and is not identified in the indictment.

The charges relate to the alleged off-label marketing of the antidepressant bupropion (marketed by GSK as Wellbutrin) for weight loss, and each carries a possible penalty of five to 20 years in prison. (...)

(Anm: Psychiatrist who was cleared by first tribunal is struck off. A psychiatrist who initially escaped sanction for falsifying documents has been struck off the UK medical register after his case was sent back to the Medical Practitioners Tribunal Service (MPTS) by the High Court. BMJ 2016;354:i5207  (Published 23 September 2016).)

US drug company executives could face criminal charges for off-label promotion
BMJ 2010; 341:c5808 (19 October)
Executives of drug companies may face charges in a criminal court if their companies promote the off-label use of drugs, an attorney for the US Food and Drug Administration has said.

The agency’s deputy chief for litigation, Eric Blumberg, speaking at a conference in Washington, DC, said, “It’s clear we’re not getting the job done with large, monetary settlements. Unless the government shows more resolve to criminally charge individuals at all levels in the company, we cannot expect to make progress in deterring off-label promotion.”

Blumberg cited Pfizer, the world’s largest drug manufacturer, for violating regulations forbidding the promotion of drugs for conditions other than those approved by the FDA. (...)

Novartis To Pay $400M In Penalties
manufacturing.net 30.9.2010
PHILADELPHIA (AP) -- Federal prosecutors say drug maker Novartis AG will plead guilty to charges it marketed an epilepsy medicine for unapproved uses and pay more than $400 million in civil and criminal penalties.

In an announcement Thursday by prosecutors in Philadelphia, the company agreed to forfeit $185 million. It also will pay $237.5 million to resolve civil liabilities over off-label marketing of Trileptal and for paying kickbacks to health care providers in a bid to get them to prescribe that and other drugs.

The Swiss company is the world's third-biggest drug maker by revenue (...)

Forest Pharmaceuticals agrees to guilty plea for violating FDA laws
worldpharmanews.com 16.9.2010
The U.S. Food and Drug Administration (FDA), working in close coordination with the U.S. Department of Justice (USDOJ), announced that Forest Pharmaceuticals, Inc. entered into a plea agreement in which the company accepted responsibility for criminal actions including distribution of an unapproved new drug, distribution of a misbranded drug, and obstruction of an FDA inspection. (...)

Forest Pharmaceuticals, Inc. also is charged with distribution of a misbranded drug for its off-label promotion of Celexa for pediatric use when it was approved only for use in adults. Celexa is the brand name for the prescription drug citalopram, a selective serotonin reuptake inhibitor (SSRI) drug for the treatment of adult depression. In addition, Forest Pharmaceuticals, Inc. also is charged with obstructing an agency proceeding because of false statements made by its employees during a 2003 FDA inspection. (...)

Systematisk bruk av legemidler utenfor godkjent indikasjon
Tidsskr Nor Legeforen 2010; 130:1452-3 (12.8.2010)
En godkjenningsordning for legemidler skal sikre at pasientene får behandling med dokumentert effekt, kvalitet og sikkerhet. Det er uproblematisk at en lege i enkelte tilfeller velger å bruke et ikke-godkjent legemiddel så lenge begrunnelsen er medisinsk. Men det at helseforetakene systematisk bruker legemidler utenfor godkjent indikasjon for å spare penger, kan føre til et dårligere behandlingstilbud for pasientene. (...)

Systematisk bruk utenfor indikasjon («off label»-bruk) og/eller bruk uten markedsføringstillatelse («off licence»-bruk) når det finnes et offentlig godkjent og dokumentert behandlingsalternativ, er en utfordring for godkjenningsordningen for legemidler og kan føre til et dårligere behandlingstilbud til pasientene (2). Står helseforetaket overfor et valg mellom flere legemidler for en gitt indikasjon, bør myndighetene være tydelige på at det godkjente alternativet skal benyttes. Dette må igjen underbygges av finansieringssystemene. Slik er det ikke i dag. (...)

Off-Label Promotions Lead to Legal Actions
medpagetoday.com 24.5.2010
Illegal promotion of an anticonvulsant drug for off-label uses has led to a criminal fine of $6.14 million against Ortho-McNeil.

The company, a subsidiary of Johnson & Johnson, will also pay $75.37 million to resolve civil allegations under the Federal False Claims Act that the illegal promotion of topiramate (Topamax) caused false claims to be submitted to government healthcare programs.

The company pleaded guilty last week in a U.S. District Court in Boston to one count of violating the Food, Drug & Cosmetic Act in connection with the off-label use.

Although no evidence was given, the court was told the company promoted Topamax for psychiatric uses, although it has never been approved to treat psychiatric disorders. The drug is licensed for the treatment of epilepsy. (...)

Off Target On Off-Label Drugs
forbes.com 12.5.2010
Americans are becoming increasingly dissatisfied with their government, according to opinion polls released in April by the Pew Research Center. The center's president, Andrew Kohut, said, "Rather than an activist government to deal with the nation's top problems, these surveys show that the general public now wants government reformed and a growing number want its power curtailed. With the exception of greater regulation of Wall Street, there is less of an appetite for government solutions to the nation's problems--including greater government control over the economy--than there was when Barack Obama first took office."

What is particularly stunning about these findings is that public sentiment is so strong while many people are unaware of important information. Consider, for example, a common aspect of U.S. medical care: doctors’ prescribing medicines "off-label"--that is, the use of approved medicines for purposes not yet sanctioned by the Food and Drug Administration (FDA). (...)

Psychoactive Drugs Rarely Prescribed for Nonpsychiatric Use
Psychiatr News 2010;45(9):16 (May 7) (American Psychiatric Association)
Over 90 percent of antidepressants and antipsychotics are prescribed for psychiatric diagnoses, even though some may be prescribed for off-label indications.

A very small minority of antidepressant and antipsychotic prescriptions and about one-third of antianxiety prescriptions are written for nonpsychiatric diagnoses, according to a recent analysis of national physician survey data. (...)

Questionable Antipsychotic Prescribing Remains Common, Despite Serious Risks
JAMA. 2010;303(16):1582-1584 (April 28)
Despite their association with serious cardiac and metabolic risks, atypical antipsychotics are widely used off-label with few data to support their efficacy, according to recent studies probing use of this class of drugs in the United States. Furthermore, physicians often do not follow through on precautions to reduce these risks.

The studies provide new insights on physician prescribing behavior and the effect of warnings aimed at minimizing risks. The findings have raised new concerns about the public health impact and costs of widespread off-label antipsychotic use. (...)

AstraZeneca to Pay $520 Million for Off-Label Drug Marketing
pharmpro.com 27.4.2010
AstraZeneca LP and AstraZeneca Pharmaceuticals LP will pay $520 million to resolve allegations that AstraZeneca illegally marketed the anti-psychotic drug Seroquel for uses not approved as safe and effective by the Food and Drug Administration (FDA), the Departments of Justice and Health and Human Services' Health Care Fraud Enforcement Action Team (HEAT) announced today. Such unapproved uses are also known as "off-label" uses because they are not included in the drug's FDA approved product label. (...)

Paxil Off-Label Use to Be Focus of Heart Defects Trial (Fokuserer på undersøkelser av hjertedefekter ved forskrivning av Seroxat (Paxil) utenfor preparatomtale)
lawyersandsettlements.com 18.4.2010
Washington, DC: Paxil manufacturer GlaxoSmithKline (Glaxo) faces hundreds of Paxil lawsuits alleging that the antidepressant causes birth defects. Next up at the plate is Delaney Novak, a little girl born on April 4, 2002 with heart defects. In June, her parents Laura and Derek will contend that misconduct on the part of Glaxo over safety warnings for Paxil caused Delaney’s birth defects. (...)

[READ MORE PAXIL ARTICLES] (LES FLERE SEROXAT-ARTIKLER) (...)

Evidence-based use of second-generation antipsychotics in a state medicaid pediatric population, 2001-2005.
Psychiatr Serv. 2010 Feb;61(2):123-9.
(...) CONCLUSIONS: The number of children receiving second-generation antipsychotics doubled in this Medicaid population between 2001 and 2005, and a large proportion of the treatments were not supported by evidence from clinical studies. (...)

Concerns Raised About Unsubstantiated Use of Antipsychotics in Children
Psychiatr News 2010;45(3):2 (February 5) (American Psychiatric Association)
Nearly half of the youth who were started on second-generation antipsychotics did not have a diagnosis for which the use was supported by published research evidence.

Second-generation antipsychotics (SGAs) are frequently prescribed for children and adolescents for a nebulous range of indications that are not approved by the Food and Drug Administration (FDA) and not supported by research evidence. (...)

Litigation uncovers biased reporting of gabapentin trials
BMJ 2009;339:b4816 (19 November)
All you need to read in the other general journals
Research documents made public during legal proceedings against drug manufacturers provide useful insights into the subtle (and often advantageous) changes that can occur between the protocol stages of a trial and final publication. When researchers recently scrutinised industry sponsored trials evaluating off-label use of gabapentin, they found that in eight of 12 trials the primary outcome in the published paper was different from the primary outcome specified in the protocol. In five trials, primary outcomes specified in the protocol were missing from the published paper. In six trials, the published paper reported a completely new primary outcome. In two trials, the primary outcome specified in the protocol was relegated to a secondary outcome in the published paper. The treatment effect (measured by the P value) and the primary outcome matched in just one of nine trials that were published in full. (...)

Trial Data on Anti-Seizure Drug Might Have Been Manipulated: Report
healthday.com 11.11.2009
Study found outcome measures differed between company documents, published reports

WEDNESDAY, Nov. 11 (HealthDay News) -- An unusual look at internal documents from a pharmaceutical company suggests that clinical data was manipulated to make a popular anti-seizure drug, gabapentin (Neurontin), look more effective than it actually was, thereby increasing possibilities for its off-label usage, according to a new report.

"This means we're not seeing the full picture, and the picture we are seeing is suspect because perhaps there was selective reporting of outcomes so that only the positive outcomes were reported," said Kay Dickersin, senior author of a paper reporting the alleged deception in the Nov. 12 issue of the New England Journal of Medicine. (...)

Outcome Reporting in Industry-Sponsored Trials of Gabapentin for Off-Label Use
NEJM 2009; 361(20):1963-1971 (November 12)
Background There is good evidence of selective outcome reporting in published reports of randomized trials. (...)

Results We identified 20 clinical trials for which internal documents were available from Pfizer and Parke-Davis; of these trials, 12 were reported in publications. For 8 of the 12 reported trials, the primary outcome defined in the published report differed from that described in the protocol. (...)

Conclusions We identified selective outcome reporting for trials of off-label use of gabapentin. This practice threatens the validity of evidence for the effectiveness of off-label interventions. (...)

Review: Reports on Pfizer Drug Studies Misleading
pharmpro.com 9.11.2009
Analysis of a dozen published studies testing possible new uses for a Pfizer Inc. epilepsy drug found that reporting of the results was often misleading, indicating the medicine worked better than internal company documents showed.

According to the report, when a company-funded study's primary finding wasn't favorable, that result was usually buried and something else positive was highlighted, without disclosing the switch. (...)

Utah AG says state gets $24M in Zyprexa settlement
forbes.com 11.11.2009 (Associated Press)
SALT LAKE CITY -- Utah Attorney General Mark Shurtleff says the state has agreed to a $24 million civil settlement with Eli Lilly & Co. over claims the drug maker engaged in off-label marketing of the anti-psychotic drug Zyprexa.

Shurtleff's office said Wednesday that it conducted a nearly four-year investigation of the drugmaker from Indianapolis.

Shurtleff says Zyprexa is approved for treatment of schizophrenia and bipolar disorder. But he says Lilly's sales force illegally promoted Zyprexa for uses not approved by the Food and Drug Administration such as dementia, Alzheimer's, agitation and depression. (...)

FDA stäms för begränsad off-label information
lakemedelsvarlden.se 6.10.2009
Företaget Allergan stämmer den amerikanska läkemedelsmyndigheten. Anledningen är att företaget vill kunna marknadsföra sitt preparat Botox utanför godkänd indikation. Begränsningar strider mot yttrandefriheten anser de. (...)

Off-label use of antipsychotic medications in the department of Veterans Affairs health care system.
Psychiatr Serv. 2009 Sep;60(9):1175-81
OBJECTIVE: This study aimed to determine the prevalence of prescribing antipsychotics to adults without schizophrenia or bipolar disorder and to identify factors associated with such off-label use. METHODS: Patients with at least one prescription for an antipsychotic medication from the Department of Veterans Affairs (VA) during fiscal year (FY) 2007 were identified in national VA administrative databases. Rates of off-label antipsychotic use were determined along with average doses. Multivariate logistic regression models identified sociodemographic and clinical characteristics associated with off-label use. (...)

CONCLUSIONS: Off-label use of antipsychotic medications was common. Given that these drugs are expensive, have potentially severe side effects, and have limited evidence supporting their effectiveness for off-label usage, they should be used with greater caution. (...)

Pfizer pays record fine for off-label promotion of four drugs
BMJ 2009;339:b3657 (9 September)
Pfizer, the world’s largest drug company, has agreed to pay $2.3bn (£1.4bn; €1.6bn) to settle charges of fraud and civil and criminal liability over its promotion of off-label use of four drugs.

The US Department of Justice said it was the largest healthcare fraud settlement in the department’s history and the largest criminal fine ever.

The New York Times noted that $2.3bn amounted to less than three weeks of Pfizer sales (www.nytimes.com, 3 Sep, "Pfizer to pay $2.3 billion to settle inquiry over marketing"). (...)

Pfizer pays $2.3B penalty for off-label drug marketing (Pfizer betaler 2,3 milliarder dollar som straff for markedsføring av legemidler utenfor preparatomtale)
fiercehealthcare.com 3.9.2009
Pfizer has agreed to pay a mammoth $3.2 billion penalty for marketing off-label uses of several of its drugs, a settlement which the U.S. Department of Justice has labeled the largest healthcare fraud settlement in the country's history.

Drugs named in the settlement, included painkiller Bextra, which has been off the market since 2005 in the wake of potential heart risks; antipsychotic Geodon; antibiotic Zyvox; and anti-epileptic drug Lyrica. (...)

Pzifer To Pay $2.3 Billion In Medicare/Medicaid Fraud Settlement (Pfizer betaler 2,3 milliarder dollar i forlik med Medicare/Medicaid om svindel)
kaiserhealthnews.org 3.9.2009
The Obama administration announced a landmark $2.3 billion health care fraud settlement with Pfizer, Inc. Wednesday, which is expected to change drug companies' promotion of off-label use of medicines. (...)

Examiner.com notes that it is "the largest fine ever levied for fraud in the Medicare and Medicaid programs. ... Pfizer will be required to pay a $1.3 billion criminal penalty in addition to a civil fine of $1 billion. The charges relate to the marketing of the painkiller, Bextra. Bextra, generic name valdecoxib, was marketed as relieving symptoms of osteoarthritis and rheumatoid arthritis in adults." (...)

Philadelphia Inquirer: "Authorities called Pfizer a repeat offender, noting this is the fourth such settlement of government charges in the last decade. The government said it would monitor the company's conduct for the next five years to rein in the abuses" (Hill, 9/3). (...)

USA VS PFIZER:
Betaler 14 mrd. i forlik

e24.no 3.9.2009
Den amerikanske legemiddelgiganten Pfizer bøyer av for myndighetene.

Ifølge flere amerikanske media skal Pfizer - verdens største legemiddelprodusent - ha inngått forlik med myndigheten, og sagt seg villig til å betale 2,3 milliarder dollar i et forlik, etter å ha markedsført legemiddelet Bextra for andre formål enn det hadde godkjenning for. (...)

Pfizer må betale 14 milliarder
nrk.no 2.9.2009
VERDENS STØRSTE: Verdens største legemiddelselskap har fått tidenes største bot i USA.

Verdens største legemiddelselskap hadde ikke dekning for det de lovet. Nå må de betale tidenes milliardbot. (...)

Den største summen, 1,3 milliarder dollar, må selskapet betale for ulovlig markedsføring av det betennelsesdempende legemiddelet Bextra. (...)

Boten er, ifølge Washington Post, den største som noen gang er ilagt i USA. (...)

Pfizer Settles Fraud Charges for $2.3 Billion (Pfizer forliker svindelanklager for 2,3 milliarder dollar)
medpagetoday.com 2.9.2009
Pfizer will pay the government $2.3 billion to settle criminal and civil charges that it promoted off-label uses for the disgraced painkiller valdecoxib (Bextra) and three other drugs.

The Justice Department said it was the largest healthcare fraud settlement in history.

More than half the settlement -- $1.3 billion -- involves Pfizer's efforts to promote valdecoxib, a COX-2 inhibitor withdrawn from the market in 2005 because of cardiovascular and other risks.

Pfizer's sales staff had urged doctors to prescribe the drug for surgical pain and to prevent deep vein thrombosis, according to court records from a criminal trial of a Pfizer manager earlier this year. (...)

Merck, Schering-Plough in $42M Vytorin settlement
pharmpro.com 6.8.2009
NEW YORK (AP) — Merck and Schering-Plough say they will pay $41.5 million to settle class-action lawsuits filed by patients taking the cholesterol drugs Vytorin and Zetia.

The lawsuits claim that the companies purposefully delayed the release of study results showing the cholesterol treatments were no more effective than older, less expensive medications. The companies do not acknowledge any wrongdoing or liability as part of the settlement.

The settlement deal comes while Whitehouse Station, N.J.-based Merck & Co. is in the process of buying Kenilworth, N.J.-based Schering-Plough Corp. for $41.1 billion. (...)

Merck, Schering-Plough Reach Vytorin Settlement With State AGs
Thompson.com 17.7.2009
Merck & Co., Schering-Plough Corp. and their cholesterol joint venture Merck/Schering-Plough Pharmaceuticals reached a civil settlement with the attorneys general (AGs) of 35 states and the District of Columbia concerning the companies’ promotion of the drugs Vytorin and Zetia and the alleged delay in releasing the results of a related clinical trial.

According to the state enforcement officials, a nearly two-year delay in the release of the full results of the so-called ENHANCE clinical trial violated state consumer protection laws. The trial determined that Vytorin, a cholesterol-lowering drug consisting of a combination of the drugs Zetia and Simvastatin, was no more effective in reducing the formation of plaque in carotid arteries than the cheaper, generically available Simvastatin alone. During the delay in the release of the trial results, the companies heavily promoted Vytorin in direct-to-consumer (DTC) advertisements. (...)

Data About Zetia Risks Was Not Fully Revealed (Data for Ezetrol (Zetia) ble ikke fullstendig offentliggjort)
nytimes.com 21.12.2007
New evidence shows that the drug makers Merck and Schering-Plough have conducted several studies of their popular cholesterol medicine Zetia that raise questions about its risks to the liver, but the companies have never published those results.

Partial results of the studies, alluded to in documents on the Food and Drug Administration’s Web site, raise questions about whether Zetia can cause liver damage when used long term with other cholesterol drugs called statins.

Most of the millions of people who use Zetia take it along with a statin like Lipitor, Crestor or Zocor. Or they take it in a single pill, Vytorin, that combines Zetia with Zocor. (...)

(Anm: Zetia (ezetimibe); markesføres i Norge under handelsnavnet Ezetrol (Zetia i i USA.)

(Anm: Vytorin (ezetimibe and simvastatin); Vytorin er en kombinasjon av Schering-Ploughs Zetia (ezetimibe; fornorsket ezetimib) og Mercks Zocor (simvastatin).)

Hemliga dokument om Seroquel släpps
lakemedelsvarlden.se 26.5.2009
I USA pågår en omfattande juridisk process där företaget Astrazeneca misstänks ha drivit en kampanj för att få läkare att förskriva preparatet Seroquel utanför godkänd indikation. Nu har en mängd tidigare hemliga dokument blivit offentliga i samband med rättegången.

ANKLAGELSER Seroquel (quetiapin) är godkänt i USA för behandling av schizofreni, bipolär depression och de maniska episoderna vid bipolär sjukdom. I USA pågår sedan en tid juridiska processer där privatpersoner stämt Astrazeneca för att medvetet ha undanhållit negativa effekter av läkemedlet.

I förra veckan gick ett antal advokatbyråer som representerar patienterna ut med ytterligare anklagelser om att företaget medvetet ska ha fört en felaktig marknadsföring för preparatet under tidigt 2000-tal. De anklagande advokaterna hävdar att företaget uppmanat läkare att förskriva Seroquel mot sjukdomar som preparatet inte var godkänt för.

Enligt amerikanska medier har dokument i form av bland annat e-post hittats där högt uppsatta personer haft för avsikt att marknadsföra Seroquel till barn och äldre, trots att det inte är godkänt i dessa åldergrupper. Flera av dessa dokument släpptes i samband med förundersökningen. (...)

Off-Label Uses of Drugs Should Be Approved for Very Ill Patients, Opinion Piece States
kaisernetwork.org 6.5.2009
FDA and Congress "should protect physicians' and patients' right" to use FDA-approved drugs for off-label uses "and for the first time allow drugmakers to promote off-label uses that prove beneficial," Richard Epstein, a law professor at the University of Chicago and a senior fellow at the Hoover Institution, writes in a Wall Street Journal opinion piece. He continues, "Right now these drugs provide immense lifesaving opportunities for many sick patients, particularly those threatened by cancer." (...)

FDA Guidelines Easing Drugmakers' Promotion of Off-Label Uses Met With Endorsements, Criticisms
kaisernetwork.org 2.2.2009
McClatchy/Philadelphia Inquirer on Monday examined guidelines released by FDA in the last week of former President George W. Bush's term that make it easier for drug manufacturers to promote "off-label" uses for prescription drugs. The use of medications for reasons not approved by FDA "has long been tolerated, and sometimes encouraged," according to McClatchy/Inquirer. It is legal for physicians to prescribe drugs for off-label uses but it is illegal for drugmakers to market drugs for off-label uses (Adams, McClatchy/Philadelphia Inquirer, 2/1). (...)

Will Bush drug rule endure?
philly.com 2.2.2009
FDA guidelines make it easier for firms to push unapproved uses of pharmaceuticals.

CORNELIUS, N.C. - In the waning days of the Bush administration, the Food and Drug Administration issued new guidelines to make it easier for drug manufacturers to promote "off-label" prescription drug uses, which can be deadly for patients.

The move came despite criticism from Bush's own Department of Veterans Affairs, which said the change "favors business interests over public safety" and could lead to a "decline in drug safety." It also was crafted despite efforts by state and federal law enforcement experts to clamp down on off-label drug marketing.

The new guidelines were issued four years after Robin Briggs of Cornelius, N.C., buried her husband, Doug, who committed suicide on a chilly Christmas Day after taking a drug off-label. (...)

Off-Label Drug Marketing Takes Some Hits

Drug companies have agreed to pay almost $7 billion in settlements that involve marketing drugs for uses other than those approved by the FDA:

 

Company

Drug

Approved use

Unapproved uses*

Settlement

2004

Pfizer

Neurontin

Epilepsy

Multiple uses, including pain, ADD, migraines

$430 million

2005

Eli Lilly

Evista

Osteoporosis

Breast cancer prevention

$36 million

2005

Serono

Serostim

AIDS wasting

Lipodystrophy, body cell mass wasting

$704 million

2006

Schering-Plough

Temodar, Intron A

Brain tumors, specific cancers, chronic hepatitis

Other tumors

$435 million

2006

InterMune

Actimmune

Immune system disorders

Lung scarring

$37 million

2007

Pfizer

Genotropin

Growth failure

Anti-aging, cosmetic use, athletic enhancement

$35 million

2007

Cell Therapeutics

Trisenox

Rare leukemia

Various cancers

$11 million

2007

Medicis Pharmaceutical

Loprox

Fungicide for those over age 10

Treatment for children under age 10

$10 million

2007

Purdue Frederick

OxyContin

Moderate, severe pain in specific instances

Wider pool of pain patients

$635 million

2007

Jazz Pharmaceuticals

Xyrem

Narcolepsy conditions

Fatigue, insomnia, pain

$20 million

2007

Bristol-Myers Squibb

Abilify

Adult schizophrenia, bipolar disorder

Pediatric use, dementia-related psychosis

$515 million

2008

Cephalon

Gabitril, Provigil, Actiq

Three different uses

Different uses for each

$425 million

2009

Eli Lilly

Zyprexa

Schizophrenia, bipolar disorder

Dementia $1.4

billion

2009

Pfizer

Bextra

Arthritis pain

Other indications

$2.3 billion

* Examples of off-label uses; settlements may be specific to just one off-label use (...)

FDA allows drug firms to distribute journal articles about unapproved uses
BMJ 2009;338:b187 (19 January 2009)
The US Food and Drug Administration has published guidance that allows drug and device companies to use reprints of journal articles about off-label, or unapproved, uses of their products in promotions to doctors.

By allowing distribution of peer reviewed but off-label studies, the FDA recognises that doctors use approved drugs and devices in unapproved situations. Once a drug or device has been approved doctors can use it as they choose. (...)

Ok för företag att distribuera vetenskapliga artiklar
lakemedelsvarlden.se 14.1.2009
Amerikanska läkemedelsverket har tillslut bestämt att det är ok för läkemedelsföretag att distribuera vetenskapliga artiklar till läkare, även om studieresultatet handlar om en effekt av läkemedlet som myndigheten ännu inte godkänt. (...)

Lax on Examining Potential Conflicts of Interest in Drug Trials, HHS OIG Report Says (Slapp granskning av mulige interessekonflikter for legemiddelforsøk, ifølge HHS OIG Report)
kaisernetwork.org 12.1.2009
The efforts of FDA officials responsible for screening physicians involved in patient trials of pharmaceutical drugs and medical devices, as part of the agency's product approval process, appear to be inadequate in identifying potential conflicts of interest, according to a report released on Monday by the HHS Office of the Inspector General, the AP/Austin American-Statesman reports. For the study, investigators examined 118 applications for newly approved medications from 2007. The study found that 42% of the applications did not disclose complete financial information and fewer than 1% of the researchers included information regarding potential conflicts of interest (Alonso-Zaldivar, AP/Austin American-Statesman, 1/12). (...)

FDA eases promotion of unapproved uses for drugs
forbes.com 12.1.2009
Food and Drug Administration officials have finalized guidelines that make it easier for pharmaceutical companies to use medical journal articles to promote drugs for unapproved uses.

The final guidelines, which have been criticized by some lawmakers as too lenient, allow companies to distribute articles about their products to doctors - even when they involve uses that have not been federally approved. (...)

FDA OKs sharing unapproved drug uses with docs
forbes.com 12.1.2009
Food and Drug Administration officials have finalized guidelines that make it easier for pharmaceutical companies to use medical journal articles to promote drugs for unapproved uses.

The final guidelines, which have been criticized by some lawmakers as too lenient, allow companies to distribute articles about their products to doctors - even when they involve uses that have not been federally approved.

The FDA document, posted online Monday, comes just days before the Bush administration turns over power to President-elect Obama's government. On the campaign trail, Obama criticized pharmaceutical industry efforts to court physicians. (...)

Questions Safety, Efficacy for Off-Label Uses of Prescription Drugs
kaisernetwork.org 26.11.2008
A new study published on Tuesday in the journal Pharmacotherapy lists 14 medications commonly prescribed for off-label uses that require additional testing to prove their safety and effectiveness for such uses, USA Today reports. According to the study -- led by Randall Stafford, an associate professor of medicine at the Stanford Prevention Research Center -- although past research has "highlighted the substantial frequency of off-label drug use without good evidence, we have identified and prioritized specific drugs warranting attention" (Rubin, USA Today, 11/25).

Researchers identified the medications on the list based on their usage, marketing, amount of associated increased risk, price and newness to the market (Wang, "Health Blog," Wall Street Journal, 11/25). Antidepressants accounted for six of the medications on the list, and antipsychotics accounted for three, with the schizophrenia treatment Seroquel, manufactured by AstraZeneca, at the top of the list. (...)

14 drugs identified as most urgently needing study for off-label use, Stanford professor says
med.stanford.edu 24.11.2008 (Stanford School of Medicine)
STANFORD, Calif. — Physicians and policy-makers know that drugs are frequently prescribed to treat certain diseases despite a lack of FDA approval — a practice known as off-label prescribing. Yet they say the problem is so big they don’t know how to begin tackling it.

But a potential game plan now exists. In a paper published in the December issue of Pharmacotherapy, a group of researchers has developed a list of 14 widely prescribed medications most urgently in need of additional study to determine how effective and safe they are for their off-label uses.

ntidepressants and antipsychotics are the most prominent classes of drugs on the list, which specifically targets drugs that have high levels of off-label use without good scientific backing. (...)

Study: Off-label drugs should be researched for safety
usatoday.com 24.11.2008
Among all the drugs prescribed to treat conditions for which they're not approved, doctors and patients should be most concerned about antipsychotics and antidepressants, a study suggests today.

This "off-label" prescribing is a legal, common practice that is being questioned in some cases because of inadequate scientific evidence to support its safety and effectiveness. (...)

Study Calls for Greater Scrutiny of 'Off-Label' Drug Use (Studie etterlyser bedre tilsyn med "forskrivning utenfor preparatomtale")
health.usnews.com 24.11.2008
Doctors often prescribe medicines for conditions that haven't been studied thoroughly

MONDAY, Nov. 24 (HealthDay News) -- It's called "off-label" prescribing, and it's the common practice of doctors prescribing a drug to treat a disease or condition that's different from the one studied by federal regulators that led to the drug's approval in the first place. påp

The new report was published in the Nov. 24 issue of the journal Pharmacotherapy.

Antidepressants and antipsychotics are the most prominent classes of drugs on the list, which specifically targets medicines that have high levels of off-label use without good scientific backing.

Quetiapine (Seroquel), et antipsykotika som topper listen, er godkjent av FDA for behandling av skizofreni. Teamet bemerket at forskrivning utenfor preparatomtale for dette legemidlet stod for 76 prosent av dets forskrivninger. (Topping the list is the antipsychotic quetiapine (Seroquel), which is approved by the FDA as a treatment for schizophrenia. The team noted that off-label use of this drug accounted for 76 percent of its prescriptions.)

Not only are their safety concerns about the drug, because of an FDA "black box" warning, but the drug costs $207 a prescription and has been marketed heavily, the study authors said. In 2004, the FDA had the drug manufacturer, AstraZeneca, add warnings about increased risks of hyperglycemia, high blood pressure and diabetes associated with use of the drug. Also, older patients with dementia-related psychosis treated with the drug are at an increased risk of death, according to the FDA.

The next four drugs on the list are the blood thinner warfarin, used off-label to treat hypertensive heart disease; the antidepressant escitalopram (Lexapro), used off-label to treat bipolar disorder; the schizophrenia drug risperidone (Risperdal), used off-label to treat bipolar disorder; and the asthma drug montelukast (Singulair), used off-label to treat chronic obstructive pulmonary disease.

Drug companies are usually prohibited from marketing their drugs for off-label use. But, they can share studies that support off-label use, the study authors said. A study published in 2006 found that of approximately 21 percent of off-label uses of drugs in 2001, 73 percent did not have adequate scientific support for the off-label use. (...)

(Anm: Nystatin and miconazole: pharmacological and clinical evidence regarding interactions with warfarin. Oral Dis. 2016 Nov;22(8):761-765. Epub 2016 Aug 8.)

Off-Label Prescriptions
ivanhoe.com 12.11.2008
(Ivanhoe Newswire) -- When your doctor prescribes a medication, you just assume it’s been fully vetted by the U.S. Food and Drug Administration (FDA).
Reported November 12, 2008

That’s not true in all cases. The FDA approves prescription drugs for specific uses. However, doctors have the right to prescribe that same drug for any use they deem appropriate. Statistics suggest “off-label” prescribing is not an isolated incidence, but happens in up to 50 percent of all prescriptions currently written in the United States.

What’s more, pharmaceutical companies may be covertly promoting the off-label use of their products to increase sales. Researchers from Washington, DC, and California suggest pharmaceutical marketing has “distorted the discourse on off-label uses and encouraged the unmonitored, potentially dangerous use of drugs by patients for whom risks and benefits are unknown.” (...)

Vanligt med marknadsföring av preparat utanför godkänd indikation
lakemedelsvarlden.se 30.10.2008
Förskrivning av läkemedel för behandling av sjukdomar utanför godkända indikationer är vanligt. Ibland är det nödvändigt men det kräver en mer noggrann uppföljning än vad som finns idag, skriver läkare i nättidningen PLoS Medicine. (...)

(Anm: Fugh-Berman A, Melnick D (2008) Off-Label Promotion, On-Target Sales. PLoS Med 5(10): e210.)

Drug Companies Push Off-Label Use
ivanhoe.com 29.10.2008
(Ivanhoe Newswire) -- In the U.S., it is legal for doctors to prescribe drugs for off-label use -- prescribing it for a condition or disease that it was not approved to treat. It is, however, illegal for drug manufacturers to promote off-label use, but two physician researchers say the companies are using covert techniques to illegally promote off-label use.

Adriane Fugh-Berman of the Georgetown University Medical Center and Douglas Melnick, a preventative medicine physician working in North Hollywood, Calif., say off-label drug use is sometimes unavoidable and in fact is sometimes “demonstrably beneficial.” But it has also been linked with serious side effects, the doctors say. (...)

Paediatricians Raise Concern Over Off-label Use of Prozac for Children
medindia.net 23.10.2008
Off-label use of psychiatric medicines like Prozac for children are becoming extensive. It could be dangerous when no systematic studies have been done on children with such medicines. (...)

Half of Doctors Routinely Prescribe Placebos (Halvparten av leger skriver rutinemessigt ut placeboer)
nytimes.com 23.10.2008
Half of all American doctors responding to a nationwide survey say they regularly prescribe placebos to patients. The results trouble medical ethicists, who say more research is needed to determine whether doctors must deceive patients in order for placebos to work. (...)

The most common placebos the American doctors reported using were headache pills and vitamins, but a significant number also reported prescribing antibiotics and sedatives. Although these drugs, contrary to the usual definition of placebos, are not inert, doctors reported using them for their effect on patients’ psyches, not their bodies. (...)

The study is being published in BMJ, formerly The British Medical Journal. One of the authors, Franklin G. Miller, was among the medical ethicists who said they were troubled by the results.

“This is the doctor-patient relationship, and our expectations about being truthful about what’s going on and about getting informed consent should give us pause about deception,” said Dr. Miller, director of the research ethics program in the department of bioethics at the National Institutes of Health. (...)

(Anm: Prescribing "placebo treatments": results of national survey of US internists and rheumatologists. BMJ 2008;337:a1938 (23 October 2008).)

(Anm: Openness and honesty in gaining fully informed consent will benefit both patients and doctors BMJ 2015;350:h1784 (Published 07 April 2015).)

About Half of U.S. Physicians Surveyed Say They Routinely Prescribe Placebos, Study Finds
kaisernetwork.org 24.10.2008
Between 46% and 58% of U.S. physicians regularly prescribe placebos to their patients, but only 5% of those physicians inform patients about the placebos, according to a survey published on Friday in BMJ, the Chicago Tribune reports. For the survey, researchers at NIH distributed questionnaires to 1,200 internists and rheumatologists nationwide (Graham, Chicago Tribune, 10/23). The Department of Bioethics and the National Center for Complementary and Alternative Medicine at NIH funded the study (Cheng, AP/Los Angeles Times, 10/24). (...)

Pfizer Finalizes $60M Settlement With States Over Off-Label Marketing of COX-2 Inhibitors
kaisernetwork.org 23.10.2008
Pfizer on Wednesday said it will pay $60 million to 33 states and Washington, D.C., to settle lawsuits that claimed the company promoted the COX-2 inhibitors Bextra and Celebrex for unapproved uses, the Miami Herald reports. The agreement is part of an $894 million settlement that the company announced last week to cover more than 90% of pending lawsuits involving the drugs. The settlement also includes $745 million to settle personal injury claims and $89 million for consumer fraud claims brought by insurers and consumers seeking to recoup money spent on the drugs.

COX-2 inhibitors drew increased scrutiny when Merck in 2004 withdrew its COX-2 inhibitor Vioxx from the market because of a link to cardiovascular risks. Celebrex is the only remaining COX-2 inhibitor on the market. (...)

Drug firms and regulatory agencies must consider how drugs are used
BMJ 2008;337:a2083 (14 October)
Safety experts have criticised drug regulators and the drug industry for not doing enough to ensure that packaging and labelling of products is safe. (...)

Læger bestemmer anvendelsen af lægemidler
lifdk.dk 18.9.2008
Det er uden hold i virkeligheden, når avisen Ingeniøren påstår, at lægemiddelindustrien opfordrer danske læger til at udskrive medicin til formål, den ikke er godkendt til.

I stort opsatte, men svagt dokumenterede, artikler har avisen Ingeniøren kritiseret lægemiddelindustrien for at påvirke lægerne til at udskrive flere typer lægemidler til områder, hvor lægemidlerne ikke er godkendt. Nu svarer Lægemiddelindustriforeningen igen. For der er ikke noget forkert i, at danske læger udskriver medicin til formål, den ikke er godkendt til. Ofte hænger det sammen med, at der ikke findes godkendte lægemidler på markedet til det givne formål, understreger Lægemiddelindustriforeningen. (...)

FDA Blamed for Poor Monitoring of Off-Label Drug Promotion
Psychiatr News 2008;43(18):1 (September 19) (American Psychiatric Association)
An audit finds that the FDA is ill equipped to catch unlawful promotion of off-label use of prescription drugs by manufacturers and, if violations are caught, is slow to take action.

The Food and Drug Administration (FDA) lacks adequate infrastructure to carry out its responsibility of regulating prescription drug marketing activities, especially promotion for unapproved ("off-label") uses, the Government Accountability Office (GAO) has found. (...)

Bruk av legemidler utenfor godkjent indikasjon
Oda Riska - Tidsskriftet
Tidsskr Nor Lægeforen 2008 (21.07.2008)
Leger kan på eget ansvar forskrive medikamenter på andre indikasjoner enn det produsentene har fått godkjent. Slik forskrivning er trolig omfattende og i USA er det anslått at 21 % av alle forskrivninger i allmennpraksis skjer utenfor indikasjon.

Et eksempel på dette er bruken av metformin ved polycystisk ovarie-syndrom, skriver Guttorm Raknes i en Kronikk i Tidsskriftet.

- Innen flere fagområder er det vanskelig å kommer utenom slik forskrivning. Særlig gjelder dette i pediatri, hvor mange legemidler bare er godkjent til bruk hos voksne, sier Raknes. (...)

Pharmaceutical Promotion to Physicians and First Amendment Rights
NEJM 358:1727-1732 (April 17)
In mid-February, the Food and Drug Administration (FDA) proposed a change in its rules governing pharmaceutical promotion that would widen the ability of drug manufacturers to distribute information on unapproved uses of their products.1 This proposal has rekindled the debate over the rights of drug makers to promote their medications to physicians. (...)

Eli Lilly E-Mail Discussed Unapproved Use of Drug
nytimes.com 15.3.2008
ANCHORAGE — John C. Lechleiter, an Eli Lilly official who is about to become the company’s top executive, wrote an e-mail message in 2003 that appears to have encouraged Lilly to promote its schizophrenia medicine Zyprexa for a use not approved by federal drug regulators. (...)

Waxman probes industry meeting with FDA (Waxman gransker industri-møte med FDA)
businessweek.com 22.1.2008
A Democratic watchdog is questioning whether drug companies are behind a government proposal that makes it easier for them to use medical journal articles in marketing drugs for unapproved uses.

According to a statement Rep. Henry Waxman made Tuesday, drug company representatives met with Food and Drug Administration officials last April to urge them to issue guidelines on distributing journal articles about off-label uses of products. Off-label uses are those that haven't been proven safe and effective. (...)

Gamle legemidler, nye muligheter
Tidsskr Nor Lægeforen 2008; 128: 62-5 (3.1.2008)
(...) Når en lege velger å bruke et legemiddel på en indikasjon som ikke er godkjent av Statens legemiddelverk eller European Medicines Agency (EMEA), skjer dette oftest i forlengelsen av legemidlets naturlige bruksområde. Det er f.eks. relativt vanlig at psykiatere bruker antidepressiver, antipsykotika og antiepileptika ved andre psykiatriske tilstander enn det som fremgår av oversikt over godkjente indikasjoner i preparatomtalene (Summary of Product Characteristics, SPC). (...)

Jus og risiko
Forskrivning av legemiddel utenfor indikasjon er ikke ulovlig og, som nevnt, vanskelig å komme utenom i enkelte fagområder. Dersom en lege velger å forskrive et legemiddel utenfor indikasjon, innebærer det et betydelig ansvar. Tidligere hadde leger ifølge den nå opphevede legeloven § 18 rett til å forskrive de legemidler som var nødvendige for virksomheten. I helsepersonelloven vil forskrivning utenfor godkjent indikasjon bli begrenset av kravene til forsvarlighet. Hva som til enhver tid er akseptert i det aktuelle fagmiljøet vil være bestemmende for hva som er forsvarlig. Med den stadig økende vektlegging av kunnskapsbasert medisin, vil dette i praksis si hva som har dokumentert effekt og sikkerhet. Utilstrekkelig dokumentert bruk av legemidler utenfor indikasjon er å anse som rent utprøvende behandling og bør skje i form av kliniske studier. I ramme 1 er det oppført noen forutsetninger for forsvarlig forskrivning utenfor indikasjon. (...)

(Anm: Flere unge bruker antidepressiva enn for ti år siden. Dette viser en ny studie fra Folkehelseinstituttet gjort i samarbeid med Høgskolen i Hedmark. Studien viser også at færre barn i 1-2-årsalderen får sovemidler. (…) Bruk av et psykofarmaka er i denne studien definert som uttak av minst én resept i løpet av et år på følgende legemidler: •sovemiddel inkludert alimemazin (Vallergan) •midler mot depresjon (antidepressiva) •midler mot psykose (antipsykotika) •angstdempende midler (anxiolytika) •midler i behandling av ADHD (fhi.no 2.2.2016).)

FDA may allow drug and device companies to promote "off-label" uses
BMJ 2007;335:1229 (15 December)
The US Food and Drug Administration (FDA) is proposing that drug and device companies can send doctors journal articles and reference materials about "off-label" or unapproved uses.

Representative Henry Waxman, the California Democrat who chairs the House of Representatives’ Committee on Oversight and Government Reform, has strongly criticised the FDA’s proposal and has posted the FDA’s draft "Guidance for Industry" document on his website together with a letter that he has sent to Dr Andrew von Eschenbach, the FDA commissioner.

"Until the Bush administration, these risks of permitting dissemination of journal articles on off-label uses were recognized by the FDA," which had expressed "grave concerns" about the practice, he wrote. (...)

FDA Considers Easing Curbs on Drug Makers Research on Off-Label Use Could Be Sent to Doctors
washingtonpost.com 1.12.2007
The Food and Drug Administration is considering allowing pharmaceutical makers to provide doctors with medical journal studies of unapproved uses for drugs, a move critics say would undermine long-standing restrictions on marketing medicines for "off-label" purposes. (...)

It's Time To Sue Doctors Who Prescribe Drugs Off-Label Part I
lawyersandsettlements.com 15.8.2007
Washington, DC: Critics say the tens of thousands of lawsuits filed against the drug giants have had little impact when it comes to dismantling the off-label drug marketing schemes and therefore, there needs to be an all out campaign of highly publicized lawsuits filed against the doctors serving as middle man pushers, one by one by one.

It is illegal for a drug company to promote a drug for uses not listed on the FDA-approved label for the simple reason that the drug maker has not successfully proven to the FDA that the drug is safe or effective for uses not listed on the label. (...)

SSRIs prescribed off-label for Sexual Problem
lawyersandsettlements.com 11.6.2007
New Brunswick, NJ: SSRIs like Zoloft have been prescribed "off-label" (that is, for something other than the purpose for which they were approved) for some time in treatment of premature ejaculation (PE). That's because these drugs notoriously turn down the sexual thermostat—among other things, they slow down ejaculation.

Europe may approve J&J's new selective serotonin reuptake inhibitor (SSRI) for premature ejaculation—but don't expect it in the U.S. any time soon. When used to treat PE, the SSRIs cause other problems. The problems are the negative side effects, such as psychiatric problems, skin reactions, weight gain and loss of libido. (...)

Dangerous practices: Off-label prescriptions
independent.co.uk 3.4.2007
Just because a drug is tested to treat one illness doesn't prove it's safe to combat other conditions. So why do doctors still prescribe 'off-label'? Jerome Burne reports

When you go to the GP, you can rest assured that any drugs you are given have been tested to make sure they work and are safe. Or can you? The fact is that hidden in medical journals are many reports showing many drugs are prescribed with no scientific evidence to show they work for the problem you've got. (...)

Most hospital kids get drugs off-label
upi.com 5.3.2007
PHILADELPHIA, March 5 (UPI) -- Nearly four out of five hospitalized children receive drugs that have been tested and approved only for adults, according to U.S. researchers.

The study -- done by members of the Pediatric Health Information Systems Research Group -- found the drugs most frequently used off-label for children were painkillers, nutrients and gastrointestinal agents. (...)

Eli Lilly The Habitual Offender
bestsyndication.com 25.1.2007
The revelations that Eli Lilly concealed the side effects of Zyprexa and promoted the drug for unapproved uses is not newly discovered misconduct. It is a persistent pattern of conduct indicative of a nasty habit that needs breaking. (...)

Indictment of Doctor Tests Drug Marketing Rules (Tiltale av lege tester regler for markedsføring)
nytimes.com 22.6.2006 (The New York Times)
At first, Dr. Peter Gleason thought his arrest was a joke. (...)

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