ZYPREXA (olanzapine) - preparatomtale (fda.gov)

– Jeg ble medisinert sykere (nrk.no 17.11.2013)

Skjulte dokumenter om alvorlige bivirkninger (aftenposten.no 13.10.2008)

Lilly betalte leger for å forskrive Zyprexa, ifølge notater (bloomberg.com 8.9.2009)

Eli Lilly hevdes å ha tonet ned risiko for bestselgende pille (nytimes.com 17.12.2006 (New York Times))

Lilly setter "profitt foran forbrukerens anliggende", sa Dr. Gueriguian på slutten av sitt fire timers vitnemål. (nytimes.com 8.3.2008)

Tre av fire pasienter avbrøt behandlingen En stor jämförande studie av Zyprexa och andra atypiska antipsykotika vid schizofreni (CATIE, 2005) rapporterade nyligen att tre av fyra patienter avbröt behandlingen i förtid, främst på grund av bristande effekt eller biverkningar. För Zyprexa avbröts behandlingen i 64 procent av fallen. Detta ger inget kraftfullt stöd för Zyprexas "effekt och säkerhet"! (Läkemedelsvärlden (November 2005))

Lilly betaler nærmere 700 millioner dollar for å forlike krav (USA TODAY 10.6.2005)

New York Times kräver kongressförhör om Zyprexa (Läkemedelsvärlden 2006(12))

Stater gransker markedsføring av Lilly-pille (States Study Marketing of Lilly Pill) (nytimes.com 20.1.2007)

Diverse alvorlige bivirkninger: parkinsonisme, diabetes, Tardive Dyskinesia (ufrivillige rørsler som kjem av sjukdom eller skade i hjernens basalgangliar... myoklonier, krampeanfall dødsfall etc. (mintankesmie.no)

Dokumenter tyder på at Lilly hemmeligholdt risiko ved legemiddel (Documents suggest Lilly concealed drug's risks) (seattletimes.nwsource.com 17.12.2006)

- Zyprexa (olanzapin) og indberetninger om dødsfald

Olanzapin og indberetninger om dødsfald
sundhedsstyrelsen.dk 31.5.2015 (NYT OM BIVIRKNINGER 2015(6) MAJ 2015)
Som led i Sundhedsstyrelsens bivirkningsovervågning har vi blandt andet fokus på antipsykotisk medicin. Vi har modtaget 50 indberetninger om død som formodet bivirkning til olanzapin – 20 af disse har vi modtaget inden for de sidste fem år. Den seneste indberetning modtog vi i juli 2014. I dette nummer af Nyt Om Bivirkninger giver vi et kort overblik over indberetningerne om dødsfald i forbindelse med behandling med olanzapin.

Gennemgang af de 50 indberettede dødsfald i forbindelse med olanzapinbe-handling

Alder
- Ukendt alder (14)
- 19-40 år (17)
- 41-60 år (10)
- Over 61 år (9)

Indberettet dødsårsag for de 50 patienter Dødsårsag

Antal

Pludselig død (dødsårsag ikke fastlagt)

14

Lægemiddelforgiftning (pludselig død)

11

Lungeemboli

10

Ukendt dødsårsag

5

Akut hjertestop

3

Eosinofil myocarditis

2

Pulmonal hypertension

1

Død af overdosis (ordineret overdosis)

1

Cerebellar blødning og sepsis (ordineret overdosis)

1

Utilsigtet overdosis pga. hukommelsestab

1

 

(Anm: Nyhedsbrevet Nyt Om Bivirkninger. (sundhedsstyrelsen.dk).)

(Anm: Sepsis; grunnleggende kliniske observasjoner (hnt.no 5.11.2013).)

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

- Få pasienter kjenner til klageordning.

(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: 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.)

- 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: «Alle» har fått avvik. Ikke ett eneste av akuttmottakene som Helsetilsynet har gjort tilsyn ved, unngikk avvik når det gjelder gjenkjennelse og behandling av sepsis. (…) Rundt 50 prosent av alle pasienter som utvikler sepsis, kommer inn via akuttmottaket. – Pasientene kommer da gjerne med en infeksjon, eller med en uavklart tilstand. (…) Sepsis som oppstår på sengepost ser ikke Fylkesmennene på i dette tilsynet. (sykepleien.no 23.2.2017).)

(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: Hvordan hjernen hjelper kroppen å bekjempe bakterier. (How the brain helps the body fight bacteria. The brain may not only control our thoughts and basic physical functions. Recent studies indicate that it also controls the way our body responds to the threat of bacterial infections. It does this by boosting the production of a protective molecule called PCTR1 that helps white blood cells kill the invading bacteria. Our body is in constant contact with bacteria. For the most part these do not pose a threat since we have evolved defence systems to keep these organisms at bay. But in some instances, especially when the body’s defence systems are weakened or fail, bacteria may invade, leading to infection and, in extreme cases, sepsis, which can result in death.) (theconversation.com 5.1.2017).)

(Anm: New Sepsis-3 Definitions Await Confirmatory Data. Since publication of Sepsis-3, substantial debate has occurred about how and when to incorporate these new definitions into practice. In February 2016, the European Society of Intensive Care Medicine and the Society of Critical Care Medicine Third International Consensus Task Force published “Sepsis-3” — new definitions for sepsis and septic shock. Sepsis is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection,” and septic shock is defined as “a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality” (NEJM JW Gen Med Mar 15 2016 and JAMA 2016; 315:775). (NEJM 2017 (December 29, 2016).)

(Anm: Drug-resistant bacteria in patients' urine or stools raise risk of drug-resistant sepsis (medicalnewstoday.com 26.4.2017).)

(Anm: Blodforgiftning: William (1) døde av sepsis fordi ingen innså hvor alvorlig situasjonen var. Opp mot 12 000 nordmenn får sepsis årlig. (dagbladet.no 14.9.2016).)

- Lundbeck-rival gør fremskridt med skizofrenimiddel. (- Midlet er en kombination af olanzapine, det tredjemest benyttede middel mod skizofreni, og en opioid-antagonist, der skal lindre nogle af bivirkningerne ved olanzapine.) (- Olanzapine bliver nemlig ikke længere anbefalet som førstelinjebehandling til den alvorlige psykiske sygdom, da medicinen har været sat i forbindelse med forøget vægt og ændringer i stofskiftet hos brugerne.)

(Anm: Lundbeck-rival gør fremskridt med skizofrenimiddel. I sit første fase 3-studie med skizofrenikandidaten ALKS-3831 har Alkermes scoret gode resultater. Midlet viser gode effekter i forhold til placebo-præparater. Det lover med andre ord godt for midlet, men der er stadig lang vej endnu. Det skriver FierceBiotech. Midlet er en kombination af olanzapine, det tredjemest benyttede middel mod skizofreni, og en opioid-antagonist, der skal lindre nogle af bivirkningerne ved olanzapine. Olanzapine bliver nemlig ikke længere anbefalet som førstelinjebehandling til den alvorlige psykiske sygdom, da medicinen har været sat i forbindelse med forøget vægt og ændringer i stofskiftet hos brugerne. Det kan blandt andet føre til type 2 diabetes. (…) Selskabet forventer resultater fra sit andet fase 2-forsøg i løbet af næste år. I det studie måler man det nye kombinationsmiddels effekt sat overfor olanzapine, når det kommer til stigninger i vægten og en række stofskifte-parametre. (medwatch.dk 3.7.2017).)

(Anm: Avdekker lovbrudd ved akuttmottak. AKUTTMOTTAK: Flere av avvikene ved tilsyn viser at pasienter med sepsis blir for dårlig observert og ikke får rask nok behandling på akuttmottaket. Alle sykehusene som hittil har vært gjenstand for tilsyn med akuttmottakenes håndtering av pasienter med blodforgiftning (sepsis), har fått avvik, som er brudd på loven. (dagensmedisin.no 21.9.2016).)

(Anm: Belgian scientists discover missing link in septic shock. Researchers at VIB and Ghent University have discovered an important mechanism of sepsis, an overreaction of the body's immune system to an infection. In this condition, the brain is unable to curb an inflammatory response, causing organ failure or 'septic shock'. This scenario is the most frequent cause of death in intensive care units. As it turns out, information about infections is passed to our brain via extracellular vesicles, small particles in brain fluid. These insights will be published in the leading scientific journal EMBO Molecular Medicine and might give rise to new strategies to treat sepsis and even other inflammatory conditions. (medicalnewstoday.com 15.9.2016).)

(Anm: - Zyprexa (olanzapin) og indberetninger om dødsfald. (…) SEPSIS. (…) Olanzapin og indberetninger om dødsfald. (sundhedsstyrelsen.dk 31.5.2015 (NYT OM BIVIRKNINGER 2015(6) MAJ 2015).)

(Anm: Snabbare vård vid blodförgiftning ska rädda liv. Svår sepsis, blodförgiftning, är vanligt förekommande och ett livshotande tillstånd som kräver snabb vård. Därför ska nu ambulanspersonal bli bättre på att identifiera patienter med sepsis. Sepsis orsakas av bakterier som sprider sig till blodbanan och leder till en allmän infektion. Kroppen utsöndrar då signalsubstanser, cytokiner, vilka påverkar kroppen på flera sätt, som höjd puls och lägre blodtryck. (netdoktor.se 10.8.2016).)

(Anm: Slideshow: What is Sepsis? Symptoms, Treatment, and More (wbmed.com 27.7.2016).)

(Anm: Simple measures cut sepsis deaths nearly in half. Sepsis, commonly called blood poisoning, is a common affliction that can affect people of all ages. A series of simple measures tested at a Norwegian hospital can make a difference in successfully treating sepsis. (medicalnewstoday.com 3.9.2016).)

(Anm: Blodförgiftning. Blodförgiftning, även kallat sepsis, är en form av infektion där bakterier har infekterat blodet. Kroppen reagerar då med ett starkt inflammatoriskt svar som i sin tur kan skada organ. Blodförgiftning är ett allvarligt, livshotande tillstånd som kan utvecklas på bara några timmar och som kräver tidig medicinsk vård. (netdoktor.se 11.4.2016).)

(Anm: Startar storkontroll av blodforgiftning på norske sjukehus. Fleire pasientar har døydd av alvorleg blodforgifting fordi dei ikkje har fått behandling i tide. (…) – Når ein får ein sepsis-tilstand er det veldig viktig at ein startar antibiotikabehandling raskt. Og det ser me ofte at sviktar, forklarar Rudi. (...) Pasienten døydde av blodforgifting som komplikasjon til strikkbehandling av hemoroidar. (nrk.no 22.6.2016).)

(Anm: Sepsis: pathophysiology and clinical management. Sepsis, severe sepsis, and septic shock represent increasingly severe systemic inflammatory responses to infection. Sepsis is common in the aging population, and it disproportionately affects patients with cancer and underlying immunosuppression. In its most severe form, sepsis causes multiple organ dysfunction that can produce a state of chronic critical illness characterized by severe immune dysfunction and catabolism. BMJ 2016;353:i1585 (Published 23 May 2016).)

(Anm: Late mortality after sepsis: propensity matched cohort study BMJ 2016;353:i2375 (Published 17 May 2016).)

(Anm: Editorial. Late mortality after sepsis. A new series of definitions of sepsis1 along with simple guidance for early diagnosis has recently been published, and a NICE guideline is due shortly.2 Sepsis is an extreme manifestation of the body responding to a severe infection—in part adaptive and protective, but potentially maladaptive and life threatening. Naturally, perhaps, the focus has been on early diagnosis and management. This is not always performed well, as highlighted by a 2015 report from the UK National Confidential Enquiry into Patient Outcome and Death.3 In a linked paper, Prescott and colleagues (doi:10.1136/bmj.i2375) report that patients who survive an episode of sepsis have a significant excess risk of mortality for a prolonged period of time.4 BMJ 2016;353:i2735 (Published 17 May 2016).)

- Symptomene tilsvarer symptomer på olanzapinforgiftning, som kan være sløvhet (fra trøtthet til koma) og/eller forvirring, desorientering, agitasjon, angst og annen kognitiv svekkelse. Andre symptomer kan være ekstrapyrimidale symptomer, som muskelstivhet eller risting og vanskeligheter med å gå og snakke, kramper, svimmelhet, økning i blodtrykk og svakhet. Symptomene kan være alvorlige og kreve sykehusinnleggelse. Derfor skal pasienter som behandles med Zypadhera observeres de første timene etter hver eneste injeksjon.

Risiko for postinjeksjonssyndrom med Zypadhera
legemiddelverket.no 21.11.2016
Pasienter som får depotinjeksjon med Zypadhera (olanzapin) skal observeres i minst tre timer etter at sprøyten er satt på grunn av risiko for alvorlige bivirkninger.

Zypadhera brukes i vedlikeholdsbehandling av schizofreni hos voksne. Legemiddelet gis som depotinjeksjon som leverer virkestoffet olanzapin inn i kroppen over en lengre tidsperiode.

Sprøyten med olanzapin skal settes i setemuskelen av helsepersonell som har trening i relevant injeksjonsteknikk. Dersom sprøyten settes feil, for eksempel inn i en blodåre isteden, kan pasienten få såkalt postinjeksjonssyndrom. Symptomene tilsvarer symptomer på olanzapinforgiftning, som kan være sløvhet (fra trøtthet til koma) og/eller forvirring, desorientering, agitasjon, angst og annen kognitiv svekkelse. Andre symptomer kan være ekstrapyrimidale symptomer, som muskelstivhet eller risting og vanskeligheter med å gå og snakke, kramper, svimmelhet, økning i blodtrykk og svakhet. Symptomene kan være alvorlige og kreve sykehusinnleggelse. Derfor skal pasienter som behandles med Zypadhera observeres de første timene etter hver eneste injeksjon.

Pasienter skal observeres av kvalifisert helsepersonell i minst 3 timer og på et sted der det er tilgang på egnet medisinsk utstyr, i tilfelle postinjeksjonssyndrom skulle oppstå.

Legemiddelverket har mottatt flere bivirkningsmeldinger om postinjeksjonssyndrom etter injeksjon med Zypadhera. Regionale legemiddelinformasjonssentre (RELIS) har mottatt flere henvendelser om Zypadhera og har kommet med praktiske anbefalinger knyttet til risikoen for postinjeksjonssyndrom.

Råd til pasienter:

  • Det er viktig at du observeres av helsepersonell etter du har fått satt sprøyten med Zypadhera i minst 3 timer, for å sikre at du får rask og riktig hjelp dersom du får alvorlige bivirkninger.
  • Ta kontakt med legen din dersom du har spørsmål om bivirkninger av Zypadhera.
  • Meld bivirkninger på Legemiddelverkets hjemmesider.

Råd til helsepersonell:

(Anm: ZypAdhera (olanzapin) (felleskatalogen.no).)

(Anm: Bloodstream Infections: The peak of the iceberg. Virulence. 2016 Apr 2;7(3):248-51. Epub 2016 Feb 18.)

(Anm: Bloodstream infection pathogens becoming more resilient. A recently published special issue of Virulence, "Bloodstream Infections", focuses on the resilience of bloodstream infections (BSI) and is endorsed by the European Study Group for Infections in Compromised Hosts of the European Society of Clinical Microbiology and Infectious Diseases. (medicalnewstoday.com 5.5.2016).)

(Anm: Blodforgiftning og Bakterier i blodet (Sepsis og Bakteriæmi) (sundhedsguiden.dk 18.9.2006).)

(Anm: - Symptomene tilsvarer symptomer på olanzapinforgiftning, som kan være sløvhet (fra trøtthet til koma) og/eller forvirring, desorientering, agitasjon, angst og annen kognitiv svekkelse. Andre symptomer kan være ekstrapyrimidale symptomer, som muskelstivhet eller risting og vanskeligheter med å gå og snakke, kramper, svimmelhet, økning i blodtrykk og svakhet. Symptomene kan være alvorlige og kreve sykehusinnleggelse. Derfor skal pasienter som behandles med Zypadhera observeres de første timene etter hver eneste injeksjon. legemiddelverket.no 25.11.2016 (legemiddelverket.no 21.11.2016).)

- Olanzapin (Zyprexa) kan ha bidratt til og / eller forverret de to rapporterte dødelige tilfeller av myokarditt.

Eosinophilic myocarditis during treatment with olanzapine - report of two possible cases.
BMC Psychiatry. 2016 Mar 17;16:70. doi: 10.1186/s12888-016-0776-y.
(…) BACKGROUND: Drug-induced eosinophilic myocarditis is a life-threatening and frequently overlooked condition. The prevalence of myocarditis in clozapine-treated patients may be as high as 3 %. An association between olanzapine and myocarditis has not previously been described, but given the chemical similarity between olanzapine and clozapine, we hypothesized the existence of such an association. We searched the spontaneous adverse drug reports database of the Danish Health and Medicines Authority for olanzapine and myocarditis in the period from October 21, 1996 to - June 03, 2015. We identified two fatal cases of eosinophilic myocarditis associated with the use of olanzapine.

CASE PRESENTATION: Case 1 was a 39-year-old Caucasian man with known substance abuse and schizophrenia. He was found dead in his home. Olanzapine was prescribed at day -54, and dose at time of death was 40 mg/day. Post-mortem toxicological examination demonstrated presence of olanzapine, morphine, venlafaxine and oxazepam. Syringes indicating substance abuse were found in his home. Case 2 was a 36-year-old Caucasian man diagnosed with schizophrenia was found dead unexpectedly. There was no history of substance abuse. Current treatment was olanzapine 20 mg/day +5 mg as PRN (prescribed for almost 4 years), aripiprazole 30 mg/day (prescribed for 6 months) and mirtazapine 30 mg/day (prescribed for 6 months). Both cases of eosinophilic myocarditis were confirmed by autopsy findings and both patients received olanzapine in doses exceeding the recommendations.

KONKLUSJON: Olanzapin (Zyprexa) kan ha bidratt til og / eller forverret de to rapporterte dødelige tilfeller av myokarditt. Ytterligere studier er nødvendig for å etablere en årsakssammenheng mellom olanzapin og eosinofil myokarditt. CONCLUSION: Olanzapine may have contributed to and/or worsened the two reported fatal cases of myocarditis. Additional studies are required to establish a causal link between olanzapine and eosinophilic myocarditis. (…)

(Anm: ABILIFY (aripiprazole) (fda.gov).)

(Anm: aripiprazole (ABILIFY) (dailymed.nlm.nih.gov).)

(Anm: Eosinophilic myocarditis: case series and literature review. Asia Pac Allergy. 2015 Apr; 5(2): 123–127. (Published online 2015 Apr 29).)

(Anm: Venlafaxine-Induced Cytotoxicity Towards Isolated Rat Hepatocytes Involves Oxidative Stress and Mitochondrial/Lysosomal Dysfunction. Purpose: Depression is a public disorder worldwide. Despite the widespread use of venlafaxine in the treatment of depression, it has been associated with the incidence of toxicities. Hence, the goal of the current investigation was to evaluate the mechanisms of venlafaxine-induced cell death in the model of the freshly isolated rat hepatocytes. (…) Conclusion: Therefore, our data indicate that venlafaxine induces oxidative stress towards hepatocytes and our findings provide evidence to propose that mitochondria and lysosomes are of the primary targets in venlafaxine-mediated cell damage. Adv Pharm Bull. 2016 Dec;6(4):521-530.)

(Anm: Akutt toksisitet for 8 antidepressiva: hva er deres virkningsmekanismer? (Acute toxicity of 8 antidepressants: what are their modes of action? Currently, the hazard posed by pharmaceutical residues is a major concern of ecotoxicology. Most of the antidepressants belong to a family named the Cationic Amphipathic Drugs known to have specific interactions with cell membranes. The present study assessed the impact of eight antidepressants belonging to selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors.) Chemosphere. 2014 Aug;108:314-9. Epub 2014 Feb 14. (PDF).)

(Anm: Cytotoxic immune cell in sick and healthy skin a key to understanding vitiligo. With the aid of thousands of skin biopsies and over a hundred kilograms of skin, researchers at Karolinska Institutet have observed how two subgroups of immune cell behave in healthy skin. This functional dichotomy is preserved in the inflammatory diseases psoriasis and vitiligo. The study, which is published in the journal Immunity, opens the way for more targeted local treatments for patchy inflammatory skin disorders. (medicalnewstoday.com 22.2.2017).)

(Anm: MR avdekker alvorlig hjertesykdom. Mer enn syv av ti mistenkte infarktpasienter som har normale funn på angiografi, har likevel en alvorlig hjertesykdom. MR avdekker sykdom hos pasienter som ofte ville ha blitt sendt hjem dagen etter og vurdert som «friske», sier seksjonsoverlege Knut Haakon Stensæth. Blant 1145 personer som ble innlagt med mistanke om akutt hjerteinfarkt ved Ullevål universitetssykehus i perioden fra mars 2007 til august 2008, hadde 4,3 prosent av dem normale kransarterier ved angiografi, mange med forhøyet troponin. Ofte sendes disse pasientene hjem uten videre oppfølging. (dagensmedisin.no 7.4.2016).)

(Anm: Hjertemuskelbetennelse (myokarditt). Myokarditt er en betennelse i hjertemuskelen, forårsaket av virus, bakterier, toksiner eller immunreaksjoner. Kan gå over uten behandling, men kan utvikles til behandlingstrengende hjertesvikt. (…) Årsaker. En myokarditt skyldes sjelden en infeksjon i hjertemuskelen. Det dreier seg i de fleste tilfeller om en immunologisk reaksjon sekundært til en infeksjon i kroppen. (…) Når kroppen reagerer med antistoffdannelse mot egen kropp, kalles tilstanden autoimmun. (…) Symptomer og tegn. Diagnosen er i mange tilfeller vanskelig å stille. Sykdomstegnene kan variere fra forstørrede lymfeknuter og uspesifikke influensaliknende symptomer, til akutt hjertesvikt med store pusteproblemer eller plutselig død. (…) Hjertemuskelbetennelse kan gi brystsmerter og derfor ligne på akutt hjerteinfarkt. Opplysninger om forutgående luftveisplager, magetarmsymptomer eller febersykdom kan være til hjelp for å se sammenhengen mellom virusinfeksjon og hjertemuskelbetennelsen. (nhi.no 28.11.2016).)

(Anm: To av tre med blodforgifting får ikkje hjelpa dei skal ha. Pasientar med blodforgifting (sepsis) blir nedprioriterte når dei kjem til akuttmottak i Helse Vest, viser rapport.  (…) Sepsis-pasientar skal få antibiotikabehandling innan ein time, etter nasjonale retningslinjer, men dei fleste får ikkje dette. (nrk.no 21.9.2016).)

(Anm: Legar sende heim alvorleg sjuk pasient. Ein erfaren kommunelege får sterk kritikk etter at ein mann blei sendt heim utan at det blei oppdaga at han var alvorleg sjuk. (…) Pasienten vart sendt heim og vart raskt dårlegare. Pasienten vart frakta til sjukehus der ein konstaterte at det var snakk om alvorleg blodforgifting. Ut frå funn ved undersøking var årsaka til blodforgiftinga uklar fram til dagen etter innlegginga, då det kom tydelege teikn. – Ved blodforgifting er det spesielt at ein ikkje har så mange timar å gå på, fortel fylkeslegen. (nrk.no 7.3.2017).)

(Anm: MITOCHONDRIAL FUNCTION IN SEPSIS. Shock. 2016 Mar;45(3):271-281.)

(Anm: Cause of immune system paralysis in sepsis identified. New insights into how the immune system can malfunction during sepsis are reported in a paper published online in Nature Immunology. The study demonstrates a new approach for reversing the paralysis of the immune system that characterizes the late stages of sepsis. (…) The team was also able to restore metabolic activity and responsiveness in white blood cells from patients with fungal sepsis by treating them with interferon-γ - a factor released by normal white blood cells responding in a healthy way. (medicalnewstoday.com 7.3.2016).)

- Patentudløb på Zyprexa (olanzapin)

Patentudløb på Zyprexa (olanzapin)
irf.dk 3.10.2011 (Institut for Rationel Farmakoterapi (IRF)
Skal olanzapin nu være førstevalg?

Mandag d. 3. oktober ser hele 8 nye generiske olanzapin-præparater dagens lys.

Zyprexa (olanzapin) er, med en omsætning på kr. 266 mio. i 2010, det til dato mest solgte antipsykotikum i Danmark - skarpt efterfulgt af Seroquel (quetiapin), der omsatte for kr. 265 mio.

Patentudløb på olanzapin betyder, at der kan opnås et årligt besparelsespotentiale på optil kr. 200 mio. - alene ved at skifte til billigste generika (baseret på priser per 3.10.2011).

I dag koster billigste parallelimporterede pakning af Zyprexa 20 mg kr. 53,91 per tablet. Til sammenligning koster det billigste generika nu kr. 2,04 per tablet. Forskellen svarer til en årlig besparelse på godt kr. 19.000 bare for en enkelt patient. For lavere doser (2,5-10 mg) er besparelsen mellem 6.400 og 8.400 kr. I 2010 blev godt 17.000 patienter behandlet med Zyprexa.

Olanzapin er nu, sammen med risperidon, det billigste valg, men er de også det bedste valg? (...)

- Olanzapin - Legemiddelreaksjon med eosinofili og systemiske symptomer (DRESS)

Olanzapine – Drug reaction with eosinophilia and systemic symptoms (DRESS)
ema.europa.eu 26.5.2016 (28 April 2016 EMA/PRAC/259909/2016 Pharmacovigilance Risk Assessment Committee (PRAC))
Recommendation
Having considered the available evidence from case reports in EudraVigilance and published case reports in the literature, the PRAC has agreed that the MAH(s) of olanzapine containing products should submit a variation within 2 months, to amend the product information as described below (new text underlined).
 
Summary of Product Characteristics
 Section 4.8. Undesirable effects Skin and subcutaneous tissue disorders Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) (frequency unknown)

Package Leaflet
4. Possible side effects
Very rare side effects include serious allergic reactions such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). DRESS appears initially as flu-like symptoms with a rash on the face and then with an extended rash, high temperature, enlarged lymph nodes, increased levels of liver enzymes seen in blood tests and an increase in a type of white blood cell (eosinophilia). (…)

(Anm DRESS syndrome stands for Drug Reaction (or Rash) with Eosinophilia and Systemic Symptoms. (en.wikipedia.org).)

(Anm: FDA sætter advarsel på Lilly-antidepressiv. De amerikanske sundhedsmyndigheder advarer nu om alvorlige hudreaktioner knyttet til Elil Lillys antipsykotiske lægemiddel Zyprexa. Der er nu kommet en ekstra advarsel på indlægssedlen hos de antipsykotiske lægemidler fra Eli Lilly, der indeholder det aktive virkemiddel olanzapine. Ifølge FiercePharma gælder det blandt andet lægemidlerne Zyprexa, Zyprexa Zydis og Zyprexa Relprevv såvel som generiske versioner, der indeholder olanzapine. (medwatch.dk 13.5.2016).)

- Danmark: Årsrapport for overvågning af bivirkninger 2015 (Zyprexa (olanzapine): Total number of fatal ADR reports: 36 (Totalt antall dødelige bivirkningsrapporter: 36).)

Årsrapport for overvågning af bivirkninger 2015 - Vilkår for brug af Drug Analysis Prints: indberettede bivirkninger
laegemiddelstyrelsen.dk (MARTS 2016)
(…) Åbenhed og dialog er nøgleord i Lægemiddelstyrelsens arbejde med bivirkninger. (…)

5.6 Indberetninger om dødsfald som formodet bivirkning til 2. generations antipsykotisk medicin
I foråret 2015 udgav Lægemiddelstyrelsen den første artikel i rækken af i alt fem artikler i vores nyhedsbrev Nyt Om Bivirkninger, hvor vi satte fokus på antipsykotisk medicin. Vi gennemgik alle dødsfald, der er indberettet som formodet bivirkning til brug af 2. generations antipsykotika. 

Oversigt over udgivelsesdato for de fem artikler i Nyt Om Bivirkninger

Overordnede analysekonklusioner En stor del af indberetningerne omhandlede patienter under 40 år, som døde pludseligt, mens de var i behandling med 2. generations antipsykotika. Mere end 30 procent af de patienter, som døde i forbindelse med behandlingen, var i samtidig behandling med ét eller flere andre antipsykotiske lægemidler. Nogle af patienterne fik yderligere behandling med benzodiazepiner. Antipsykotisk polyfarmaci er i uoverensstemmelse med den gældende vejledning for behandling med antipsykotika (Sundhedsstyrelsens gældende vejledning om behandling med antipsykotiske lægemidler til personer over 18 år med psykotiske lidelser nr.9276 af 6. maj 2014). (…)

(Anm: Drug Analysis Prints: indberettede bivirkninger. (…) Oversigt over antal bivirkninger, indberetninger og dødsfald (laegemiddelstyrelsen.dk).)

(Anm: Olanzapine: Drug Safety Communication - FDA Warns About Rare But Serious Skin Reactions. A search of the FDA Adverse Event Reporting System (FAERS) database identified 23 cases of DRESS reported with olanzapine worldwide since 1996, when the first olanzapine-containing product was approved. FAERS includes only reports submitted to FDA, so there are likely to be additional cases about which FDA is unaware. One patient taking olanzapine experienced DRESS and died; however, this patient was taking multiple medicines that could also have contributed to death (see the Data Summary section of the Drug Safety Communication for more information). (fda.gov 5.5.2016).)

- Dommen fra USA omfatter også tvilsom markedsføring og salg av preparatet til pasienter på feil indikasjon

Skjulte bivirkningsfare
nettavisen.no 12.10.2008
MÅ BETALE: Legemiddelet som Eli Lilly har solgt viser seg å være risikofyllt og dyre for selskapet.

Legemiddelkonsernet Eli Lilly er dømt til å betale 62 millioner dollar i erstatning for å ha skjult risiko for alvorlige bivirkninger av legemiddelet Zyprexa.

Dommen fra USA omfatter også tvilsom markedsføring og salg av preparatet til pasienter på feil indikasjon. (...)

Mange hevder blant annet de har utviklet diabetes som følge av Zyprexa. Resultatet er at 33 stater saksøkte Eli Lilly blant annet for ulovlig markedsføring, og for å ha solgt preparatet til pasienter som ikke trengte det. (...)

Hemliga papper om Zyprexa blir offentliga
lakemedelsvarlden.se 9.9.2008
Företaget Eli Lilly är föremål för en omfattande utredning i USA. Det handlar om det antipsykotika läkemedlet Zyprexa och allvarliga biverkningar som företaget anklagas för att ha dolt.

Rättsligt Det är en federal domare i Brooklyn som i fredags beslöt att offentliggöra hemligstämplade dokument om storsäljaren Zyprexa (olanzapin).

Bakgrunden är att ett antal försäkringsbolag, pensionsfondsbolag och fackföreningar har krävt Eli Lilly på stora skadestånd på grund av biverkningar av Zyprexa som företaget dolt. (...)

- Dødsfald indberettet som formodet bivirkning til Zypadhera® (Olanzapin depotinjektion (Zypadhera®) og post injektionssyndrom) i USA

Dødsfald indberettet som formodet bivirkning til Zypadhera® (- Olanzapin depotinjektion (Zypadhera®) og post injektionssyndrom) i USA
sundhedsstyrelsen.dk 29.6.2014
I juni 2013 informerede Sundhedsstyrelsen om, at de amerikanske sundhedsmyndigheder, FDA, havde fået indberettet to uventede dødsfald. Begge patienter havde fået en indsprøjtning med Zypadhera® mod skizofreni 3-4 dage, før de døde. Blodprøver fra de afdøde patienter viste høje koncentrationer af olanzapin, men det kunne ikke afklares, hvorvidt der var en sammenhæng mellem dødsfaldene og medicinen. Læs meddelelsen fra juni 2013 på vores hjemmeside: FDA undersøger sikkerheden ved skizofreni-medicinen Zypadhera. (…)

- Hemming av autofagi avdekker nevrotoksisk virkning for antipsykotika olanzapin (Zyprexa).

Autophagy inhibition uncovers the neurotoxic action of the antipsychotic drug olanzapine.
Autophagy. 2014 Dec 31:0. [Epub ahead of print]
Abstract We investigated the role of autophagy, a controlled cellular self-digestion process, in regulating survival of neurons exposed to atypical antipsychotic olanzapine. Olanzapine induced autophagy in human SH-SY5Y neuronal cell line, as confirmed by the increase in autophagic flux and presence of autophagic vesicles, fusion of autophagosomes with lysosomes, and increase in the expression of autophagy-related (ATG) genes ATG4B, ATG5, and ATG7. The production of reactive oxygen species, but not modulation of the main autophagy repressor MTOR or its upstream regulators AMP-activated protein kinase and AKT1, was responsible for olanzapine-triggered autophagy. Olanzapine-mediated oxidative stress also induced mitochondrial depolarization and damage, and the autophagic clearance of dysfunctional mitochondria was confirmed by electron microscopy, colocalization of autophagosome-associated MAP1LC3B (LC3B henceforth), and mitochondria, and mitochondrial association with the autophagic cargo receptor SQSTM1/p62. While olanzapine-triggered mitochondrial damage was not overtly toxic to SH-SY5Y cells, their death was readily initiated upon the inhibition of autophagy with pharmacological inhibitors, RNA interference knockdown of BECN1 and LC3B, or biological free radical nitric oxide. The treatment of mice with olanzapine for 14 d increased the brain levels of autophagosome-associated LC3B-II and mRNA encoding Atg4b, Atg5, Atg7, Atg12, Gabarap, and Becn1. The administration of the autophagy inhibitor chloroquine significantly increased the expression of proapoptotic genes (Trp53, Bax, Bak1, Pmaip1, Bcl2l11, Cdkn1a, and Cdkn1b) and DNA fragmentation in the frontal brain region of olanzapine-exposed animals. These data indicate that olanzapine-triggered autophagy protects neurons from otherwise fatal mitochondrial damage, and that inhibition of autophagy might unmask the neurotoxic action of the drug. (…)

(Anm: Mitochondria (mitokondrie) (mitokondriesykdommer) (mitokondrielle sykdommer). (mintankesmie.no).)

(Anm: Linking telomere loss and mitochondrial dysfunction in chronic disease. (…) Drawing a mechanistic connection between telomere function and mitochondria biology will provide a broader perspective for understanding the pathophysiology of diseases and their relation to the aging process, and may provide opportunities for new possible treatments. Front Biosci (Landmark Ed). 2017 Jan 1;22:117-127.)

(Anm: Extreme short and long telomeres linked to increased cancer risk (news-medical.net 5.4.2017).)

(Anm: Scientists discover master regulator of cellular aging. (…) "Telomeres represent the clock of a cell," said TSRI Associate Professor Eros Lazzerini Denchi, corresponding author of the new study, published online in the journal Science. "You are born with telomeres of a certain length, and every time a cell divides, it loses a little bit of the telomere. Once the telomere is too short, the cell cannot divide anymore." (medicalnewstoday.com 13.1.2017).)

(Anm: Betennelser endrer mitokondrier til giftige fabrikker. Å lære hvordan å kontrollere betennelser kan ha store implikasjoner for behandlingen av mange sykdommer. Banebrytende forskning oppdager hvordan makrofager endrer mitokondriene til giftige kjemisk-produserende betennelsespromotører. (Inflammation turns mitochondria into toxic factories. Learning how to control inflammation could have huge implications for the treatment of many diseases. Breaking research discovers how macrophages turn mitochondria into toxic chemical-producing inflammation-promoters.) (medicalnewstoday.com 25.9.2016).)

(Anm: Research may show new ways to repress inflammation at outset. (…) Professor Alexander Weber of the Interfaculty Institute of Cell Biology says the enzyme - Bruton's tyrosine kinase or BTK - is switched on when an inflammation occurs in the body, playing a key role in the inflammation's subsequent development. (medicinenet.com 21.2.2017).)

(Anm: Ørsmå mitokondrier spiller en svært stor rolle mht. menneskets evolusjon og sykdom (Tiny mitochondria play outsized role in human evolution and disease.) (medicalnewstoday.com 25.9.2015).)

(Anm: Loss of Mitochondrial Function Impairs Lysosomes. J Biol Chem. 2016 Mar 17. pii: jbc.M115.695825. [Epub ahead of print].)

(Anm: Lysosome. A lysosome (derived from the Greek words lysis, meaning "to loosen", and soma, "body") is a membrane-bound cell organelle found in most animal cells (they are absent in red blood cells).  (en.wikipedia.org).)

- Skjulte dokumenter om alvorlige bivirkninger

Skjulte dokumenter om alvorlige bivirkninger
aftenposten.no 13.10.2008
Legemiddelprodusent godtok rekordforlik i USA. Mange nordmenn bruker medisinen.

Et skred av pasientklager mot legemiddelkonsernet Eli Lilli førte til at selskapet ble saksøkt av 33 amerikanske stater. (...)

Søksmålet gikk blant annet ut på ulovlig markedsføring og for å ha solgt preparatet til pasienter som ikke trengte det, skriver Helsebiblioteket.no.

Nå har Eli Lilly akseptert å betale 62 millioner dollar i erstatning for å skjult dokumentasjon om alvorlig bivirkningsfare ved bruk av legemiddelet Zyprexa, og for å ha oppfordret leger til å skrive ut legemiddelet til personer som ikke trengte det. Selskapet må også frigi alle forskningsresultater om Zyprexa. (...)

Hyppigst rapportert er bivirkninger i nervesystemet, som svimmelhet, kramper og parkinsonlignende symptomer sier Kvande.

Interne dokumenter viser at Eli Lilly satset aggressivt på å få Zyprexa inn på markeder legemiddelet ikke er godkjent for, blant annet til medisinering av eldre pasienter med demens, ifølge the New York Times. (...)

Zyprexa er heller ikke godkjent til bruk på unge under 18 år. Studier på pasienter viste flere uønskede reaksjoner, blant annet vektøkning og forandringer i stoffskiftet.

En intern epost tyder imidlertid på at selskapet vil overtale helsepersonell til å behandle ungdommer med legemiddelet, skriver avisen. (...)

I begynnelsen av oktober varslet Eli Lilly at Zyprexa vil bli merket med advarsel om risiko for vektøkning, økt blodsukker, forhøyet kolestrolverdi og andre stoffskifteproblemer.

Til nå har selskapet hevdet at Zyprexa ikke avviker fra andre tilsvarende preparater når det gjelder bivirkninger. (...)

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

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

(Anm: Legemiddelindustrien (Big Pharma) (mintankesmie.no).)

(Anm: USAs mest beundrede lovbryter. (America's Most Admired Lawbreaker ) I løpet av 20 år utviklet Johnson & Johnson et kraftig legemiddel, promoterte det ulovlig overfor barn og eldre, skjulte bivirkninger og tjente milliarder av dollar. Dette er innsidehistorien. (Over the course of 20 years, Johnson & Johnson created a powerful drug, promoted it illegally to children and the elderly, covered up the side effects and made billions of dollars. This is the inside story.) (huffingtonpost.com 8.10.2015).)

(Anm: Tjenestemenn anklaget også firmaene for at de i markedsføringen av legemidler til barn hadde unnlatt å opplyse om at Risperdal (risperidone) kan føre til hormonelle ubalanser som kan føre til brystvevutvikling og infertilitet (barnløshet) hos gutter og jenter. I markedsføringen av legemidlet for behandling av eldre mennesker med demens hadde firmaet opprettet et salgsteam for omsorg for eldre, til tross for at data fra en studie finansiert av Janssen som viste at risperidon doblet risikoen for dødsfall blant eldre mennesker, ifølge statlige tjenestemenn. BMJ 2015;351:h7018 (Published 31 December 2015).)

(Anm: - Således ble bruk av antipsykotika knyttet til en doblet risiko for lungebetennelse hos pasienter med AD (Alzheimers sykdom), og til og med en høyere relativ risikoøkning (3,43 ganger) blant dem uten AD. (…) Resultatene indikerer at bruk antipsykotika er knyttet til en høyere risiko for lungebetennelse uavhengig av alder, anvendt studiedesign, behandlingsvarighet, valg av legemidler eller samtidige sykdommer. (dgnews.docguide.com 30.8.2016).)

(Anm: Among antidementia drugs, memantine is associated with the highest risk of pneumonia. A recent study from the University of Eastern Finland shows that among users of antidementia drugs, persons using memantine have the highest risk of pneumonia. The use of rivastigmine patches is associated with an increased risk as well. (medicalnewstoday.com 24.11.2016).)

(Anm: Publikum ønsker tøffere straffetiltak mot uansvarlig atferd i næringslivet. (- Resultatene viste en sterk offentlig bekymring for skjevhet i rettssystemet) (theconversation.com 25.7.2016).)

(Anm: Superrike skattesnytarar. (…) Denne verksemda vil ikkje ta slutt før dei som legg til rette for hemmeleghald og skatteunndraging – bankar, advokatar og rådgjevarar – opplever ein reell risiko for å bli straffa for å utføre slike tenester.) (dn.no 3.7.2017).)

(Anm: EU-kommissionen visste om VW-fusket. (- Misstankarna inom kommissionen väcktes till liv när dess experter insåg att luftkvaliteten i städer inte förbättrades som förväntat efter de strängare utsläppskraven för bilar som infördes 2007, enligt Der Spiegel.) (nyteknik.se 15.7.2016).)

(Anm: Volkswagen mistenkt for å ha villedet EUs investeringsbank. Volkswagen er mistenkt for å ha brukt et lån fra Den europeiske investeringsbanken (EIB) til å utvikle teknologi som åpnet for juks med utslippstester. Sjefen for den europeiske investeringsbanken (EIB) Werner Hoyer er skuffet over Volkswagen. (dn.no 2.8.2017).)

(Anm: VW-chef erkänner bedrägeri. En högt uppsatt chef på tyska Volkswagen (VW) i USA, inblandad i avgasskandalen, erkänner bedrägeri, meddelade en talesperson för domstolen i Detroit på tisdagen. (nyteknik.se 26.7.2017).)

(Anm: VW-topp sier seg skyldig – risikerer 169 år i fengsel. Den tidligere VW-toppen i USA, Oliver Schmidt, innrømmer å ha forsøkt å dekke over utslippsjukset. Nå risikerer han mange år bak murene. (tv2.no 28.7.2017).)

(Anm: Tidligere Volkswagen-ingeniør dømt til fengsel. En tidligere ingeniør i Volkswagen får 40 måneders fengsel etter Volkswagen-skandalen. (vg.no 25.8.2017).)

(Anm: Dieselskandalen truer tysk økonomi. Den tyske dieselskandalen utgjør en risiko for landets økonomi, opplyser Tysklands finansdepartement i en rapport mandag. Dieselskandalen oppsto for nesten to år siden, da det ble kjent at Volkswagen jukset med utslippstallene. Her monterer tyske arbeidere dieselmotorer på en Volkswagen-fabrikk i Chemnitz i Tyskland. (dn.no 21.8.2017).)

(Anm: -1200 vil dø av utslipp fra Volkswagens «juksebiler». Amerikanske forskere har undersøkt konsekvensene av utslippsjuks. (…) Det er forskere ved universitetet MIT i USA som har sett nærmere på konsekvensene av Volkswagens utslippsjuks. (dagbladet.no 3.3.2017).)

(Anm: Dieseljuks. Forskere har funnet den skjulte koden i juksebilene til Volkswagen. Gikk langt for å hindre at det var mulig å teste det virkelige utslippet. (…) Nå har de funnet svaret, gjemt i programvaren til bilene, melder University of California San Diego. (…) Resultatene er publisert i en rapport (PDF), som blir lagt frem frem under IEEE Symposium on Security and Privacy i San Francisco denne uken. Under vanlig bruk, slipper bilene ut inntil 40 ganger mer NOx enn tillatt. Utslippsavsløring: Skrur av eksosrensingen allerede ved 17 grader (tu.no 23.5.2017).)

(Anm: Research. The Volkswagen Emissions Scandal Could Shorten Thousands of Lives, Study Says (time.com 3.3.2017).)

(Anm: VW-sjef pågrepet i USA En høytstående sjef i Volkswagen i USA har i kjølvannet av dieselskandalen blitt pågrepet av FBI, mistenkt for bedrageri, ifølge The New York Times. Oliver Schmidt ble ifølge den amerikanske avisa pågrepet lørdag. (nrk.no 9.1.2017).)

(Anm: Volkswagen må betale 36 milliarder kroner etter utslippsjukset. (aftenposten.no 11.1.2017).)

(Anm: Volkswagen trolig spart for milliarder i USA. En dommer i USA har avvist et søksmål mot Volkswagen, noe som kan spare den tyske bilprodusenten for milliarder av dollar i utbetalinger. Avgjørelsen kan avskrekke en rekke amerikanske stater fra å saksøke Volkswagen etter utslippsskandalen som har fulgt bilprodusenten i nesten to år. Den føderale dommeren Charles Breyer avviste søksmålet fra delstaten Wyoming med henvisning til at den aktuelle forurensningsloven må reguleres sentralt og ikke av de amerikanske delstatene. (dn.no 1.9.2017).)

(Anm: Tysk avis: VW-sjefen godkjente dekkoperasjon. Martin Winterkorn, avgått konsernsjef i Volkswagen, godkjente en plan om å holde tilbake informasjon fra amerikanske myndigheter, skriver Bild. (e24.no 26.9.2016).)

(Anm: VW må betale 2,8 milliarder dollar i bot for dieseljuks. Beløpet tilsvarer over 24 milliarder kroner. (dagbladet.no 21.4.2017).)

(Anm: Nobelprisvinner trekker seg fra Panama-gransking. (…) Begrunnelsen er at granskingen vanskeliggjøres av hemmelighold og manglende åpenhet.) (…) Pieth sier det blant annet finnes beviser for hvitvasking av penger fra barneprostitusjon i Panama-dokumentene. (dn.no 6.8.2016).)

(Anm: Margaret McCartney: Valgfri offentliggjøring av utbetalinger er meningsløst. (Margaret McCartney: Optional disclosure of payments is pointless.) (- Og åpenhet anskueliggjør problemene: bør de som mottar tusenvis av pund fra industrien som "påtenkte ledere" sitte i paneler for utarbeidelse av nasjonale retningslinjer eller hjelpe til med å stake ut regjeringens politikk?) BMJ 2016;354:i3692 (Published 01 July 2016).)

(Anm: For mange retningslinjer for behandlinger er skrevet av eksperter med finansielle konflikter, viser studien. (statnews.com 22.8.2016).)

(Anm: Naturlig at dette er offentlig. OUS-lege Elisabeth Gulowsen Celius samtykket til offentliggjøring av honorarer. Hun er kritisk til kolleger som ikke har gjort det samme. – Det kan reise spørsmål om det er bindinger som ikke tåler dagens lys. (dagensmedisin.no 12.8.2016).)

(Anm: Resultater publisert i JAMA Internal Medicine antyder at ett enkelt gratis måltid kan øke sannsynligheten for at en lege vil foreskrive et bestemt legemiddel. (Findings published by JAMA Internal Medicine suggest that even a single free meal can boost the likelihood a doctor will prescribe a certain drug) (online.wsj.com 20.6.2016).)

(Anm: FDAs rådgivere på opioider sparket grunnet bånd til industrien, ifølge AP. (FDA's advisers on opioids booted for ties to industry, AP learns. Having been buffeted by controversy over its approval of addictive opioid drugs, the FDA is calling on a panel of experts to help it sort through the thorny issue. But even before the new panel met, it has been tinged by controversy itself, dismissing four advisers because of perceived ties to drugmakers.) (fiercepharma.com 8.7.2016).)

(Anm: Offentliggjøring av verdioverføringer. Legemiddelindustrien offentliggjør i dag alle verdioverføringer til helsepersonell og helseforetak. (lmi.no 30.6.2016).)

(Anm: Leder. Disclosure UK: åpenhet (offentliggjøring) bør ikke lenger være valgfritt BMJ. (Editorials. Disclosure UK: transparency should no longer be an optional extra) BMJ 2016;354:i3730 (Published 06 July 2016).)

(Anm: Disclosure UKs nettsted gir en "illusjon av åpenhet", sier Goldacre (Disclosure UKs nettsted gir en "illusjon av åpenhet", sier Goldacre) (Disclosure UK website gives “illusion of transparency,” says Goldacre) BMJ 2016;354:i3760BMJ 2016; 354 (Published 06 July 2016).)

(Anm: Reporting of financial and non-financial conflicts of interest by authors of systematic reviews: a methodological survey. (…) Conclusions Although close to half of the published systematic reviews report that authors (typically many) have conflicts of interest, more than half report that they do not. Authors reported individual conflicts of interest more frequently than institutional and non-financial conflicts of interest. BMJ Open 2016;6:e011997.)

(Anm: - Legene som deklarerte de høyeste inntektene fra legemiddelfirmaer i Storbritannias nye database uttaler at åpenhet om utbetalingene bør være obligatorisk. (The doctors who declared the most earnings from drug companies in the United Kingdom’s new database have said that being transparent about payments should be mandatory.) BMJ 2016;354:i3716 (Published 04 July 2016).)

(Anm: Leger som mottar de største utbetalingene fra legemiddelfirmaer deklarerer dem ikke på nytt nettsted. (Doctors getting biggest payments from drug companies don’t declare them on new website. BMJ 2016;354:i3679 (Published 01 July 2016).)

(Anm: Association between payments from manufacturers of pharmaceuticals to physicians and regional prescribing: cross sectional ecological study. BMJ 2016;354:i4189 (Published 18 August 2016).)

(Anm: Medisinsk utstyr (mintankesmie.no).)

(Anm: Legemiddelprodusenter og medisinske utstyrsprodusenter betalte i fjor 6,5 milliarder dollar til leger og undervisningssykehus. (Drug and device makers paid $6.5 billion to docs and teaching hospitals last year.) (statnews.com 30.6.2016).)

(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: Bivirkninger og bivirkningsovervåkning (legemiddelsikkerhet) (mintankesmie.no).)

(Anm: Skader og ulykker i Norge. 2500 dør og 300 000 behandles årlig på sykehus for skader. Mange alvorlige skader er knyttet til alkohol og andre rusmidler, fall og trafikk. (…) Hva er et forgiftningsdødsfall? (fhi.no 14.12.2016).)

(Anm: Medisinske feil — den tredje viktigste dødsårsaken i USA. Hvert år oppstår mer enn 250 000 dødsfall i USA som et resultat av medisinske feil. Medisinske feil inkluderes ikke i dødsattester eller i rangeringen av dødsårsaker. (Medical error—the third leading cause of death in the US.) BMJ 2016;353:i2139 (Published 03 May 2016).)

(Anm: RE: Studier som stikkes under stol Minileder Tidsskr Nor Legeforen 2015; 135:617 (25.5.2015).)

(Anm: RE: Psykisk syke lever kortere. Tidsskr Nor Legeforen Tidsskr Nor Legeforen 2015; 135:246 – 8 (8.09.2015).)

(Anm: RE: Psykisk syke lever kortere. Tidsskr Nor Legeforen 2015; 135:1534 – 5 (22.9.2015).)

(Anm: RE: Psykisk syke lever kortere. Tidsskr Nor Legeforen Tidsskr Nor Legeforen 2015; 135:1923-4 (17.11.2015).)

- Heteslag  under behandling med olanzapin (Zyprexa), trihexyphenidyl, og trazodon hos en pasient med schizofreni.

Heat stroke during treatment with olanzapine, trihexyphenidyl, and trazodone in a patient with schizophrenia
Acta Neuropsychiatr. 2015 Dec;27(6):380-5.
(…) OBJECTIVE: Heat stroke is a medical emergency. Psychiatric patients are particularly susceptible to heat stroke. Therefore, awareness and preventive measures of heat stroke are important for both clinicians and patients. Case description A 49-year-old man with schizophrenia, who was under maintenance treatment with olanzapine 20 mg/day, trihexyphenidyl 4 mg/day, and trazodone 50 mg/day, suffered from heat stroke in a heat wave and required intensive care. He recovered with the medical treatment provided. Discussion Several factors could have contributed to the impaired thermoregulation and the occurrence of heat stroke in this case: schizophrenia, the psychotropic regimen, and lack of preventive measures. Possible differential diagnoses of heat stroke in this case include infection, neuroleptic malignant syndrome, and serotonin syndrome.

CONCLUSION: Heat stroke can occur during the maintenance treatment of olanzapine, trihexyphenidyl, and trazodone for schizophrenia. Clinicians should be proactive to reduce the risk of heat stroke in psychiatric patients. (…)

(Anm: Trihexyphenidyl (Artane, Apo-Trihex, Parkin, Pacitane), also known as benzhexol and trihex, is an antiparkinsonian agent of the antimuscarinic class. It has been in clinical usage for decades. (en.wikipedia.org).)

(Anm: Trazodone (sold under many brand names worldwide[1]) is an antidepressant of the serotonin antagonist and reuptake inhibitor (SARI) class. (en.wikipedia.org).)

(Anm: Uriktig fremstilling av skader i studier på antidepressiva. Nye bevis fra kliniske studierapporter avdekker feilklassifisering, feiltolkning, og underrapportering av alvorlige skader. BMJ 2016;352:i217 (Published 28 January 2016).)

(Anm: Offentligt betalte forskere pynter på resultater af forsøg på mennesker. (videnskab.dk 14.3.2016).)

(Anm: Helsevesenet bruker ikke ny forskning. Norske pasienter får medisiner og behandling de ikke har bruk for fordi nye forskningsresultater ikke tas i bruk. Større problem enn unyttig forskning, mener eksperter. (forskning.no 2.1.2016).)

(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: Lederartikler (Editorials) Tid for kunnskapsbasert forskningspolitikk Og offentlig finansierte forskere må være åpne om den sannsynlige betydningen av forskningen. (Time for evidence based research policy. And publicly funded researchers need to be candid about the likely impact of research). BMJ 2016;353:i3146 (Published 13 June 2016).)

(Anm: Kronikk: Kari Sollien, leder i allmennlegeforeningen. Hvorfor bruker ikke kommunene legenes kunnskap? Kunnskap skal redde velferdsstaten. I kommunene har ledelsen en lang vei å gå for å involvere helsepersonell i arbeidet med å utvikle helsetjenesten. (dagensmedisin.no 15.8.2016).)

(Anm: Leger ivaretar din mentale helse, men hvem ivaretas deres? (Doctors look after our mental health but who looks after theirs?) (theconversation.com 26.4.2016).)

(Anm: Dorothea Dix: Redefining mental illness. During the 19th century, mental health disorders were not recognized as treatable conditions. They were perceived as a sign of madness, warranting imprisonment in merciless conditions. One woman set out to change such perceptions: Dorothea Lynde Dix. (…) Dix - a teacher and nurse during the American Civil War - tirelessly campaigned for the fair treatment of patients with mental health disorders, after being appalled by the conditions in which they were confined. (medicalnewstoday.com 5.5.2017).)

(Anm: Tor K. Larsen, professor i psykiatri, Stavanger universitetssykehus: - Den valgfriheten som helseministeren nå ønsker å påtvinge helsevesenet vil føre til at mange svært alvorlig syke mennesker i praksis fratas retten til best mulig behandling. Innføring av medikamentfrie poster i psykiatrien er et gigantisk feilgrep. (dagensmedisin.no 29.7.2016).)

(Anm: Tre av 60.000 studenter ble tvunget til å slutte. Medstudenter og lærere varsler for sjelden om personer som ikke egner seg til yrket de utdanner seg til, mener fagfolk. Studenter som skal jobbe med mennesker og sårbare grupper, bør ikke ha rusproblemer, psykiske problemer, dårlige kommunikasjonsevner eller holdninger som ikke er forenlig med yrket. (aftenposten.no 18.8.2016).)

(Anm: - Hvorfor legers mentale helse bør være en bekymring for oss alle. (- Noen av de mer alarmerende resultater av å ha stressede og deprimerte leger er patologisk kynisme, en uvilje mot å ta vare på kronisk syke og redusert empati.)  (newstatesman.com 16.4.2016).)

(Anm: 27% of Medical Students Are Depressed. In the new research published in the Journal of the American Medical Association, researchers analyzed nearly 200 studies of 129,000 medical students in 47 countries. They found that 27% of medical students had depression or symptoms of it, and 11% reported suicidal thoughts during medical school. (time.com 10.12.2016).)

(Anm: LEDER. Ville du like å gå til en lege som er psykopat? Tidsskr Nor Legeforen 2008; 128:1805 (28.8. 2008).)

(Anm: Psychopathy of 1,800 prisoners leads to novel diagnostic tool for criminals and non-criminals alike (medicalnewstoday.com 12.8.2016).)

(Anm: Introduction and validation of Psychopathic Personality Traits Scale (PPTS) in a large prison sample. Conclusion. This brief measure of psychopathic traits uncontaminated with behavioral items can be used in the same way among participants with and without criminal history. Journal of Criminal Justice 2016;46: 9–17 (September 2016).)

(Anm: Kronikk av anonym far: Min datter ble et offer for pillepsykiatrien. (aftenposten.no 25.8.2015).)

(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: Klager: Fylkeslegen – Helsetilsynet (Statens helsetilsyn) - Fylkesmannen - Fylkesnemndene for barnevern og sosiale saker (mintankesmie.no).)

- 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.)

Post injektionssyndrom
sundhedsstyrelsen.dk 29.6.2014
Under kliniske forsøg blev der hos nogle patienter set symptomer svarende til overdosering efter en injektion med olanzapin. Reaktionerne opstod ved < 0,1 % af injektionerne og hos ca. 2 % af patienterne. 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. De initiale tegn og symptomer på denne reaktion viste sig i de fleste tilfælde inden for en time efter injektionen. For alle tilfældene var der bedring efter 24-72 timer. (...)

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

- FDA gransker to pasienters dødsfall på Zyprexa Relprevv

FDA probes deaths of two patients on Lilly schizophrenia drug (FDA gransker to pasienters dødsfall på Lillys legemiddel mot schizofreni)
reuters.com 18.6.2013
(Reuters) - Den amerikanske legemiddelkontrollen Food and Drug Administration sa på tirsdag at de gransket dødsfallet til to pasienter som døde etter injeksjoner med Eli Lilly og Cos langtidsvirkende behandling for schizofreni kalt Zyprexa Relprevv. (The U.S. Food and Drug Administration on Tuesday said it was investigating the deaths of two patients who died following injections with Eli Lilly and Co's long-acting treatment for schizophrenia, called Zyprexa Relprevv.)

Kontrollorganet sa at pasientene døde tre til fire dager etter å ha mottatt en passende dose av legemidlet, og hadde veldig høye nivåer av det injiserbare legemidlet i deres blodbane. (The agency said the patients died three to four days after receiving an appropriate dose of the medicine, and had very high levels of the injectable drug in their bloodstreams.)

Legemidlets pakningsvedlegg har en fremtredende "black box"-advarsel om at postinjeksjon delirium sedasjon syndrom (PDSS), en alvorlig tilstand der legemidlet kommer inn i blodet for fort etter en injeksjon som forårsaker sterkt forhøyede nivåer av legemidlet i blodet.(The medicine's package insert label carries a prominent "black box" warning of post-injection delirium sedation syndrome (PDSS), a serious condition in which the drug enters the blood too fast following an injection, causing greatly elevated levels of the drug in the bloodstream.)

FDA skriver i en nyhetsmelding på sin hjemmeside at høye doser av legemidlet kan forårsake delirium, hjerte-lunge-stans, sedasjon og koma. (The FDA, in a bulletin on its website, said high doses of the drug can cause delirium, cardiopulmonary arrest, heart rhythm problems, sedation and coma.)

Legemidlet godkjent av FDA på slutten av 2009 kommer med advarsler om at pasienter må bli værende på legekontoret i minst tre timer etter at det er gitt så de kan bli overvåket. (...) (The medicine, approved by the FDA in late 2009, comes with warnings that patients must stay at the doctor's office for at least three hours after it is given so they can be monitored.)

(Anm: FDA Probes Deaths Linked to Long-Acting Zyprexa (medpagetoday.com 18.6.2013).)

- Post injektionssyndrom

Post injektionssyndrom
sundhedsstyrelsen.dk 29.6.2014
Under kliniske forsøg blev der hos nogle patienter set symptomer svarende til overdosering efter en injektion med olanzapin. Reaktionerne opstod ved < 0,1 % af injektionerne og hos ca. 2 % af patienterne. 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. De initiale tegn og symptomer på denne reaktion viste sig i de fleste tilfælde inden for en time efter injektionen. For alle tilfældene var der bedring efter 24-72 timer. (...)

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

(Anm: Zyprexa Relprevv (Olanzapine Pamoate): Drug Safety Communication - FDA Investigating Two Deaths Following Injection (fda.gov 18.6.2013).)

FDA undersøger antipsykosemedicin efter dødsfald
medwatch.dk 19.6.2013
To amerikanske patienter er døde efter at have taget antipsykosemedicin fra en større medicinalkoncern. FDA indleder nu en formel undersøgelse af sagen.

De amerikanske sundhedsmyndigheder, FDA, indleder nu en formel undersøgelse af en sag, hvor to patienter er døde få dage efter at have taget antipsykosemedicinen, Zyprexa Relprevv. Det oplyser myndighederne i en e-mail.

Medicinen med det generiske navn olanzapine pamoate kommer i form af en intramuskulær injektion, som skal gives ved et af en række certificerede centre i USA, da patienterne skal holdes under opsyn i minimum 3 timer efter indsprøjtningen.

Lægemidlet er nemlig forbundet med en øget risiko for at udvikle post-injection delirium sedation syndrome (PDSS) – en yderst alvorlig tilstand, hvor det pågældende stof bliver optaget alt for hurtigt i blodet efter en intramuskulær injektion, hvilket kan føre til såkaldt delirium eller i værste fald sende patienten i koma.
Det vides endnu ikke, om medicinen er skyld i de to dødsfald, men begge patienter havde store mængder olanzapine i blodet, viser en foreløbig undersøgelse.

Antipsykosemedicinen markedsføres af medicinalgiganten Eli Lilly i USA. (...)

(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).)

- Han ville legge seg, men stupte i stuegulvet før han kom så langt.

Kåre (94) trodde han fikk vitaminer av hjemmehjelpen - fikk schizofrenimedisin
nrk.no 13.3.2015
Kaare André Kopperud ble alvorlig syk etter at han ved en feil fikk levert medisin for schizofreni og bipolar lidelse av hjemmehjelpen fra Oslo kommune. Hjemmehjelpen hadde gått til feil hus og feil pasient. (…)

Kopperud tok medisinene, av det som viste seg å være 30 mg Olanzapin den kvelden, og dagen etter begynte han å føle seg dårlig.

Han ville legge seg, men stupte i stuegulvet før han kom så langt. (…)

Det visste seg at Kopperud hadde fått medisinen Olanzapin som er beregnet på personer med bipolar lidelse og schizofreni i en høy dose. (…)

– Det er grov svikt, sier Helge Refsum, overlege og prof.dr.med ved Diakonhjemmet sykehus. Han er ekspert på psykofarmakologi og jobber med å analyse mengde av virkestoffer i blodet til pasienter.

– Olanzapin er et medikament som er ment for personer med schizofreni og bipolar lidelse, sier Refsum. Det er et legemiddel som brukes i psykiatrien til pasienter med psykisk sykdom forklarer han.

Kopperud fikk i seg 30 mg, noe som hadde vært mye for en voksen mann på 40 år forklarer Refsum.

– En engangsbruk i høy dose vil først og fremst gjøre at pasienten blir trett, sløvhet, nedsatt bevissthet, kanskje bevisstløs og i verste fall koma, sier Refsum.  (…)

(Anm: Zyprexa (olanzapine). (mintankesmie.no).)

- Fylkeslegen ber om svar på hvordan 94-åring kunne få schizofrenimedisin

Fylkeslegen ber om svar på hvordan 94-åring kunne få schizofrenimedisin
nrk.no 16.3.2015
Fylkeslegen i Oslo og Akershus har opprettet tilsynssak i forbindelse med at Kaare Kopperud fikk utlevert schizofrenimedisin han ikke skulle ha av hjemmehjelpstjenesten i Oslo kommune.

Fylkeslege Petter Schou vil nå ha en redegjørelse fra Bydelsledelsen i Frogner i Oslo på hvordan dette kunne skje. (…)

Fredag fortalte NRK om 94 år gamle Kaare Kopperud som fikk levert feil medisin på døra av hjemmehjelpstjenesten. Medisinen er ment for personer med bipolar lidelse og schizofreni og var en høy dose. Kopperud ble bevisstløs og lå på gulvet i stua i nesten et døgn før han klarte å trykke på alarmknappen som hang rundt halsen.

I dag sendte fylkeslege Petter Schou et brev til Frogner bydel i Oslo kommune med kopi til byrådsavdelingen. (…)

Diverse artikler

– Jeg ble medisinert sykere
nrk.no 17.11.2013
Thea Røstbakken (19) har siden hun var 12 år tatt så mange medikamenter at hun opplever at hun har vært dopa hele ungdomstida si. – Jeg ble dårligere under behandling, og det er psykiatriens ansvar, sier hun.

Thea Røstbakken (19) drømmer om å bli lege eller psykiater for å hjelpe andre. – Jeg ønsker bidra med en stemme i psykiatrien som er basert på erfaring.

I et innlegg på NRK Ytring skriver Thea Røstbakken om en ungdomstid fylt av store mengder antidepressiva og tøffe møter med psykiatrien.

Nå er hun 19 år, og føler at hun har gått glipp av en viktig og formende del av livet.

– Jeg var dopa ned hele ungdomstida mi. Det oppleves urettferdig, fordi ting kunne vært gjort så annerledes, sier hun.

Les også: Psykisk helsevern i krise
Les også: Dramatisk økning i bruk av antidepressiva blant unge jenter (…)

– Tett oppfølging er viktig
Steinar Madsen, hjertespesialist - Medisinsk fagdirektør i Legemiddelverket, Steinar Madsen, sier god oppfølging er essensielt. - Foto: NRK /

Medisinsk fagdirektør i Legemiddelverket, Steinar Madsen, sier god oppfølging er essensielt.
Foto: NRK
Medisinsk fagdirektør i Legemiddelverket, Steinar Madsen, bekrefter at legemiddelet Zyprexa ikke er anbefalt til barn og unge, men sier at preparatet brukes i tilfeller der det anses som nødvendig. (...)

Sykehuset beklager
NRK har sett Theas journaler og vært i kontakt med lederen for avdelingen ved sykehuset der hun ble behandlet fra hun var 12 år.

De bekrefter at hun var pasient hos dem og at hun fikk utskrevet flere medisinske preparater i perioden hun var inne til behandling der, også Zyprexa.

Ifølge sykehuset er det ikke vanlig praksis å behandle en 12-åring med dette legemiddelet. (...)

(Anm: Pillene er ikke problemet - Jeg har gått på antidepressiva siden jeg var 12. Pillene skulle behandle en mengde symptomer, men forårsaket flere nye. (nrk.no 16.11.2013).)

Recruitment to drug trials (Rekruttering til legemiddelforsøk)
Investigating the fallout of a suicide (Granskning av etterspill etter selvmord)
BMJ 2013;347:f6039 (8 October 2013)
In 2004 Dan Markingson committed suicide while he was taking part in the CAFE psychiatric trial. Edward Davies looks at how his death has been dealt with
Almost a decade has passed since Dan Markingson committed suicide while taking part in the CAFE psychiatric drug trial at the University of Minnesota.
After years of pressure and countless fruitless personal and legal battles, however, campaigners still believe that his story is only half told and earlier this year launched a petition demanding Minnesota governor Mark Dayton independently investigate the case.1

The petition makes some grave allegations: “Evidence of fraud and serious privacy violations in psychiatric studies at the university have emerged,” it claims.
“It is possible that other research subjects have died or suffered serious injuries, or that they have been mistreated in other ways. Bioethicists at the University of Minnesota itself have called for an external investigation, yet the university still refuses.”

Nine years of struggle
To understand the most recent developments it’s important to note that many of the protagonists have been at loggerheads since Markingson first entered the CAFE trial in 2003.

Markingson began to show signs of paranoia and delusions in 2003, believing that he needed to murder his mother. He was committed to Fairview Hospital involuntarily after evaluation and was subsequently enrolled on a clinical trial of antipsychotic drugs. This study was a comparison of atypical antipsychotics for the treatment of first episodes of schizophrenia (the CAFE study). The study’s structure was that of a Phase 4 randomized, double blind trial comparing the effectiveness of three different atypical antipsychotic drugs: Zyprexa (olanzapine), Risperdal (risperidone) and Seroquel (quetiapine), with each patient to be treated for a year.

After about two weeks on study treatment in the hospital, Markingson was discharged to a halfway house. His mother, Mary Weiss, raised repeated concerns about his condition, questioning his involvement in the trial, but he eventually committed suicide on 7 May 2004. (...)

Olanzapine-induced eccrine squamous syringometaplasia
Am J Dermatopathol. 2012 Jun;34(4):434-7
Abstract Eccrine squamous syringometaplasia is a histopathologic pattern that has mainly been described in patients receiving chemotherapy. Its association to nonchemotherapeutic agents is rare, with very few cases reported in the literature. We present the case of a 55-year-old patient with schizophrenia, who developed a skin eruption 5 weeks after initiating treatment with olanzapine. The histopathologic study revealed squamous syringometaplasia of the dermal eccrine ducts. (...)

Zyprexa loss hurts Lilly but forecast upped
pharmatimes.com 27.7.2012
Eli Lilly has posted double-digit declines in sales and earnings for the second quarter, hit by patent expiries on the antipsychotic Zyprexa, but the results were better than expected.

Net income sank 23% to $923.6 million, also hit by restructuring costs, while turnover came in at $5.60 billion, down 10%. The best performer was the antidepressant/fibromyalgia blockbuster Cymbalta (duloxetine), which stormed up 22% to $1.22 billion, while the lung cancer drug Alimta (pemetrexed) increased 8% to $659.5 million. The insulin products Humalog and Humulin increased 4% and fell 3% respectively, to $613.4 million and $303.0 million.

Zyprexa (olanzapine) had turnover of $379.5 million, a fall of 73% (and down 96% in the USA to just $29.8 million). The osteoporosis drug Evista (raloxifene), which is also approved for the prevention of breast cancer for certain postmenopausal women, edged up 1% to $265.9 million, while sales of Lilly’s other osteoporosis drug Forteo (teriparatide) increased 20% to $276.4 million. The erectile dysfunction drug Cialis (tadalafil) slipped 2% to $469.5 million, while the attention-deficit hyperactivity disorder drug Strattera (atomoxetine) generated $153.0 million of sales, down 3%. (...)

16 psykiatriske patienter fik firedobbelt bedøvelse
politiken.dk 29.6.2012
(...) Store doser normalt
1.015 patienter fik fra 1.1.-15.3. det antipsykotiske middel olanzapin (Zyprexa).

Af dem fik 335 doser over vejledningens.

88 patienter blev fra 1.1. til 1.6. behandlet med det beroligende middel Midazolam.

46 af dem i Glostrup, hvor den gennemsnitlige dosis var 17,9 mg. (...)

OVERDOSERING. 88 psykiatriske patienter er blevet behandlet med midlet Midazolam i doser, der overskred det anbefalede.

»Patientsikkerheden har været sat på spil«, skriver psykiatridirektør i informationsbrev til patienter, pårørende og ansatte.

I årets første fem måneder er 88 psykiatriske patienter blevet behandlet med det beroligende middel Midazolam i doser, der klart har overskredet de maksimale, og det er sket, uden at lægerne har haft en vejledning for, hvordan lægemidlet skulle bruges.

16 af patienterne har fået det beroligende middel, der får patienterne til at synke sammen og falde i søvn, i doser, der var mindst fire gange de normale maksimale doser. (...)

Patentudløb på Zyprexa (olanzapin)
irf.dk 3.10.2011 (Institut for Rationel Farmakoterapi (IRF)
Skal olanzapin nu være førstevalg?

Mandag d. 3. oktober ser hele 8 nye generiske olanzapin-præparater dagens lys.

Zyprexa (olanzapin) er, med en omsætning på kr. 266 mio. i 2010, det til dato mest solgte antipsykotikum i Danmark - skarpt efterfulgt af Seroquel (quetiapin), der omsatte for kr. 265 mio.

Patentudløb på olanzapin betyder, at der kan opnås et årligt besparelsespotentiale på optil kr. 200 mio. - alene ved at skifte til billigste generika (baseret på priser per 3.10.2011).

I dag koster billigste parallelimporterede pakning af Zyprexa 20 mg kr. 53,91 per tablet. Til sammenligning koster det billigste generika nu kr. 2,04 per tablet. Forskellen svarer til en årlig besparelse på godt kr. 19.000 bare for en enkelt patient. For lavere doser (2,5-10 mg) er besparelsen mellem 6.400 og 8.400 kr. I 2010 blev godt 17.000 patienter behandlet med Zyprexa.

Olanzapin er nu, sammen med risperidon, det billigste valg, men er de også det bedste valg? (...)

Lilly enjoys good quarter ahead of Zyprexa patent expiries
pharmatimes.com 22.7.2011
Eli Lilly has posted a 11% decline in earnings for the second quarter, but sales were up 9%, thanks again to the performances of the antidepressant/fibromyalgia blockbuster Cymbalta and the lung cancer drug Alimta.

Net income was $1.20 billion, hit by higher marketing and administrative expenses, plus costs associated with the company’s recently-announced diabetes collaboration with Boehringer Ingelheim. Sales came in at $6.25 billion.

Revenues from Cymbalta (duloxetine) were up 16% to $1.00 billion, while the cancer drug Alimta (pemetrexed) increased 11% to $613.4 million. Lilly’s best-selling drug continues to be the antipsychotic Zyprexa (olanzapine), which had turnover of $1.40 billion, up 12%. (...)

FDA Drug Safety Communication: Antipsychotic drug labels updated on use during pregnancy and risk of abnormal muscle movements and withdrawal symptoms in newborns (Meddelelse fra FDA om legemiddelsikkerhet: Oppdatert preparatomtale for antipsykotika ved bruk under svangerskap og risiko for unormale muskelbevegelser og seponeringsymptomer hos nyfødte.)
fda.gov 22.2.2011
Safety Announcement (Sikkerhetsmeddelelse)
(...) The U.S. Food and Drug Administration (FDA) is informing healthcare professionals that it has updated the Pregnancy section of drug labels for the entire class of antipsychotic drugs. The new drug labels now contain more and consistent information about the potential risk for abnormal muscle movements (extrapyramidal signs or EPS) and withdrawal symptoms in newborns whose mothers were treated with these drugs during the third trimester of pregnancy.

Antipsychotic drugs are used to treat symptoms of psychiatric disorders such as schizophrenia and bipolar disorder, and have been shown to improve daily functioning in individuals with these disorders. Common brand names for antipsychotic drugs include Haldol, Clozaril, Risperdal, Zyprexa, Seroquel, Abilify, Geodon, and Invega (see List of Antipsychotic Drugs below). (...)

(Anm: New study to help people withdraw from inappropriate long-term antidepressant treatment. One in 10 adults are being given antidepressants each year, but up to 50 per cent of patients could be given an alternative treatment, a University Professor suggests. (…) "We appreciate that stopping antidepressants is not easy," he said. "Withdrawal symptoms, including anxiety and low mood, are usually temporary but feel similar to the reason why patients were first put on antidepressants. (…) Professor Kendrick added: "Antidepressant prescribing rates are rising very quickly and some don't need to be prescribed at all. (medicalnewstoday.com 27.7.2016).)

Summary Box: Key drugs boost Lilly 2Q performance
forbes.com 22.7.2010
SECOND-QUARTER NUMBERS: Indianapolis drugmaker Eli Lilly and Co. earned $1.35 billion, or $1.22 per share. That's up from $1.16 billion, or $1.06 per share, in the same period last year. Revenue rose 9 percent to $5.75 billion. (...)

KEY FACTORS: Revenue growth from top-selling drugs like the antipsychotic Zyprexa and the antidepressant Cymbalta helped Lilly overcome pricing cuts in Europe and a $70-million hit from the U.S. health care reform law. (...)

Caution on Zyprexa in Adolescents
fda.gov (April 2010 April 2010)
The FDA is recommending that healthcare professionals use caution when considering Zyprexa (olanzapine) for treating adolescents 13 to 17 years old for schizophrenia and bipolar disorder.

Physicians, patients and caregivers should understand that adolescents may experience weight gain and hyperlipidemia with Zyprexa. In fact, they have a greater risk of these effects than adults. They are likely to gain more weight than adults and have greater increases in total cholesterol, LDL cholesterol, triglycerides, prolactin, and hepatic transaminase levels. Adolescents are also more likely to experience sedation than adults. Clinicians should take these effects into account when deciding on antipsychotic medications for adolescents, and they may want to consider trying other drugs first.

If Zyprexa is prescribed for adolescents, it should be part of a comprehensive treatment program that often includes psychological, educational and social components. It is also important to note that Zyprexa has not been approved for patients under the age of 13. (...)

(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.)

Zyprexa (olanzapine) tablet, orally disintegrating tablets and IM injection
fda.gov 18.2.2010
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) – January 2010

WARNINGS
Hyperprolactinemia
As with other drugs that antagonize dopamine D2 receptors, olanzapine elevates prolactin levels, and the elevation persists during chronic administration. Hyperprolactinemia may suppress hypothalamic GnRH...

Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, a factor of potential importance if the prescription of these drugs is contemplated...

In placebo-controlled olanzapine clinical studies (up to 12 weeks), changes from normal to high in prolactin concentrations were observed in 30% of adults treated with olanzapine as compared to 10.5% of adults...
In placebo-controlled olanzapine monotherapy studies in adolescent patients (up to 6 weeks) with schizophrenia or bipolar I disorder (manic or mixed episodes), changes from normal to high in prolactin concentrations... (...)

(Anm: hyperprolaktinemi; for rikeleg danning av prolaktin skuldast oftast større eller mangfaldige små svulstar i hypofysen (sjå prolaktinom), stress, visse medikament eller hypotalamussjukdom, kan hos kvinna gi mjølkerenning og menstruasjonsskiplingar, hos menn vert det gjerne veik kjønnshelse med sviktande libido, dårleg reisning og endra sædavgang. EN hyperprolactinemia. Kilde: Norsk medisinsk ordbok.)

FDA Advises Caution in Olanzapine Use in Teens
Clinical Psychiatry News 2009;38(1):1 (January 2010)
The approval of olanzapine for two pediatric indications—the treatment of schizophrenia and of manic or mixed episodes associated with bipolar I disorder in adolescents aged 13 to 17 years—comes with a precaution.

The Food and Drug Administration is advising clinicians to consider the increased potential for weight gain associated with the antipsychotic in adolescents, compared with adults.

Olanzapine (Zyprexa) was approved in December for the two indications based on two short-term studies—one, a 6-week trial of 107 adolescents with schizophrenia; the other, a 3-week study of 161 adolescent inpatients and outpatients with manic or mixed episodesassociated with bipolar I disorder.

The indications section of the revised label for both bipolar I disorder and schizophrenia includes the following statement: “When deciding among the alternative treatments available for adolescents, clinicians should consider the increased potential (in adolescents as compared with adults) for weight gain and hyperlipidemia. Clinicians should consider the potential long-term risks when prescribing to adolescents, and in many cases, this may lead them to consider prescribing other drugs first in adolescents.” (...)

(Anm: Unmotivated to exercise? Dopamine could be to blame. (…) Examining dopamine receptors in mice. Researchers set out to examine dopamine signaling in lean and obese mice, and the findings were published in the journal Cell Metabolism. (…) They found that the D-2 type receptor (D2R) binding, found in the striatum, was reduced in obese mice. This was consistent with previous research in rodents. (…) Although "there are probably other factors involved as well, the deficit in D2 is sufficient to explain the lack of activity," says Danielle Friend, first author of the study and former NIDDK postdoctoral fellow. Kravitz mentions that his future research will examine the connection between diet and dopamine signaling. Kravitz and team will investigate whether unhealthful eating affects dopamine signaling, and how quickly mice recover to normal activity levels once they start eating healthfully and losing weight. (medicalnewstoday.com 2.1.2017).)

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. (...)

Lilly Paid Doctors to Prescribe Zyprexa, Notes Show (Update2) (Lilly betalte leger for å forskrive Zyprexa, ifølge notater)
bloomberg.com 8.9.2009
Sept. 8 (Bloomberg) -- Eli Lilly & Co. paid doctors in South Carolina for participating in a speakers’ program in exchange for prescribing the antipsychotic Zyprexa, and used golf bets to get more patients on the drug, according to notes by sales representatives.

During a golf game, one doctor agreed to start new patients on Zyprexa for each time a sales representative parred, or put the ball in a hole within a predetermined number of strokes, according to the notes.

“I got four pars out of nine holes,” Lilly salesman Vince Sullivan said in a February 2002 note. “I said I wanted my four new patients.” (...)

Lilly resolved a marketing investigation over Zyprexa in January with the U.S. Justice Department, promising to pay $1.42 billion, including about $362 million to more than 30 states. South Carolina opted not to join that settlement. (...)

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

Psykisk syge får nej til erstatning
politiken.dk 24.5.2009
To danskere har fået erstatning for bivirkninger ved den mest udbredte medicin mod skizofreni. I USA er tallet 30.000.

Det mest solgte lægemiddel til danskere med skizofreni har været centrum for et gigantisk retsopgør i USA de senere år, hvor producenten har udbetalt erstatning til 30.000 amerikanere for potentielt dødelige bivirkninger ved medicinen Zyprexa.

Herhjemme har blot to patienter fået erstatning for bivirkninger ved præcis samme lægemiddel.

»USA har en helt anden tradition for retssager om bivirkninger ved lægemidler. Det kan være forklaringen på, at der har været så mange erstatningssager derovre og så få i Danmark«, siger overlæge Anders Fink-Jensen, der er formand for Dansk Psykiatrisk Selskab og klinikchef på Rigshospitalets psykiatriske afdeling. (...)

Patientforsikringen oplyser, at den i perioden 2003-2009 har modtaget 18 klager fra enkeltpersoner over bivirkninger ved Zyprexa. Det svarer til tre klager om året i gennemsnit.

De har blandt andet klaget over, at de er blevet overvægtige af Zyprexa. 16 sager er afgjort, og i langt de fleste får klagerne at vide, at de ikke er berettiget til erstatning. Kun to patienter har fået medhold.

Trods sagerne i USA ser Lægemiddelstyrelsen ingen grund til at mistænke Zyprexa for at være farlig.

»Vores vurdering af effekt og sikkerhed bygger ikke på retssager i et andet land. De bygger på forskningsresultater og indberettede bivirkninger fra Danmark og resten af Europa«, siger overlæge Doris Stenver fra Lægemiddelstyrelsen. (...)

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

Eli Lilly to Continue Schizophrenia Drug Program In Spite Of "Inconclusive" Study Results
pharmpro.com (1.4.2009)
INDIANAPOLIS (AP) — Eli Lilly & Co. said Sunday it will continue developing a potential schizophrenia treatment and considered recent midstage study results "inconclusive" after the drug candidate was no more effective than placebo. (...)

The company plans to start another midstage clinical trial on mGlu2/3.

Leerink Swann analyst Seamus Fernandez called the results a "serious blow" to Eli Lilly's pipeline.

"We believe any additional studies (with the drug candidate) should be viewed as exploring the mGlu2/3 mechanism, but the agent should not move forward into Phase III studies due to safety concerns," he said, in a note to investors. (...)

Eli Lilly to continue schizophrenia drug program
forbes.com 30.3.2009 (Associated Press)
Eli Lilly & Co. said Sunday it will continue developing a potential schizophrenia treatment and considered recent midstage study results "inconclusive" after the treatment candidate was found to be no more effective than placebo. (...)

In all 669 patients enrolled and 393 completed the study. None of the four doses of MGlu2/3 were more effective than placebo.

Eli Lilly also said the already approved anti-psychotic Zyprexa was no more effective than placebo when given in 15-milligram doses, once-daily. Zyprexa has previously proved more effective than placebo.

The company plans to start another midstage clinical trial on mGlu2/3. (...)

Lilly's Zyprexa/Prozac Combo Approved for Depression
pharmexec.findpharma.com 25.3.2009
Eli Lilly, on Monday, received approval to market its bipolar disorder treatment Symbyax—a combination of the antipsychotic Zyprexa and the antidepressant Prozac—to patients suffering from treatment-resistant depression (TRD). Symbyax becomes the first drug approved for TRD.

Symbyax was approved as a bipolar treatment in 2003, and Lilly has been trying diligently to expand its indications to patients with that haven’t responded to traditional drug therapies.

“We define treatment-resistant depression patients as people who fail to respond to at least two different anti-depressants in their current episode of depression,” said Sara Corya, medical director at Eli Lilly. “You can imagine, that a patient at that stage is thinking that nothing is going to work for them. Those are the folks that we feel will be appropriate for Symbyax.” (...)

Keeping us safe from drug reps
philly.com 27.1.2009
Eli Lilly and its "off-label marketing" of Zyprexa is not the only case of drug firms risking patients' health and lives. (...)

Lilly Looks Beyond Loss To Prasugrel
forbes.com 29.1.2009
Charges have sunk the company to a loss in the last two quarters, but hope is on the horizon.

Eli Lilly posted its second consecutive quarterly loss as Zyprexa sales continued to weaken and the acquisition of ImClone weighed heavy on its balance sheet. But investors are looking to next week, when Lilly may find out if it can fill its coffers with a new blockbuster. (...)

The fourth quarter was Lilly's second consecutive loss. It posted a loss in the third quarter due to a $1.4 billion charge related to a Zyprexa settlement. (See "Lilly Admits $1.4 Billion Zyprexa Mistake.") The Indianapolis-based company admitted guilt in a misdemeanor violation of the Food, Drug and Cosmetic Act for its improper marketing of Zyprexa to elderly patients with dementia during the period of September 1999 to March 2001. While Lilly did not admit guilt in the civil investigation related to these charges, it agreed to pay a total of $1.4 billion in settlements, and entered into a corporate integrity agreement with the Office of Inspector General of the U.S. Department of Health and Human Services. (...)

Lilly Admits $1.4 Billion Zyprexa Mistake
forbes.com 30.1.2009
The big pharmaceutical firm pays out for its past marketing missteps.

Eli Lilly was the picture of remorse on Thursday, when the pharmaceutical company admitted to the improper marketing of its antipsychotic drug Zyprexa, agreeing to pay more than $1.4 billion in settlements.

The Indianapolis-based company admitted guilt in a misdemeanor violation of the Food, Drug and Cosmetic Act for its improper marketing of Zyprexa to elderly patients with dementia during the period of September 1999 to March 2001. (...)

Lilly nears $1.4B Zyprexa agreement, report says
forbes.com 14.1.2009
Drugmaker Eli Lilly and Co. is close to agreeing to a $1.4 billion settlement related to a government investigation into the marketing of its top seller Zyprexa, according to a New York Times report.

The Times reported Wednesday on its Web site that an agreement could be reached as soon as Thursday. (...)

But the Times reported in late 2006 that confidential documents show Lilly downplayed the drug's risks and marketed it for unapproved uses.

Lawsuits have made similar claims, accusing Lilly of pushing doctors to prescribe Zyprexa for "off-label" conditions like Alzheimer's disease. Doctors are free to prescribe drugs for unapproved uses, but pharmaceutical companies are prohibited from marketing them for those uses. (...)

Lilly Said to Be Near $1.4 Billion U.S.
Settlement

nytimes.com 14.1.2009
Eli Lilly, the drug company, is expected to agree as soon as Thursday to pay $1.4 billion to settle criminal and civil charges that it illegally marketed its blockbuster antipsychotic drug Zyprexa for unauthorized use in patients particularly vulnerable to its risky side effects. (...)

FDA not prepared to approve long-acting Zyprexa just yet
pharmatimes.com 8.1.2009
Eli Lilly has suffered a setback with the news that US regulators have delayed a decision on whether to approve a long-acting version of the blockbuster schizophrenia drug Zyprexa.

Lilly said that it has received a complete response letter from the US Food and Drug Administration (FDA) for Zyprexa (olanzapine) long-acting injection (LAI) for acute and maintenance treatment of schizophrenia in adults. The firm noted that the agency does not require any additional clinical trials for the continued review of the New Drug Application. (...)

Minnesota becomes latest to sue Lilly over Zyprexa
forbes.com 3.11.2008
INDIANAPOLIS - Minnesota has joined a long line of states aiming to wrangle money from Eli Lilly and Co. with a lawsuit over the drugmaker's top seller, the anti-psychotic Zyprexa.

The state attorney general's office filed a complaint in federal court last week echoing claims of other lawsuits that say Lilly downplayed the drug's side effects and marketed it for uses not approved by federal regulators.

Lilly has spent more than $1.1 billion since 2005 to settle product liability claims regarding the drug, which brought in more than $4.7 billion in revenue last year. It announced last month a $62 million settlement with 32 states and Washington, D.C., over Zyprexa marketing practices. (...)

Eli Lilly boosts adjusted 2008 profit forecast
forbes.com 23.10.2008 (Associated Press)
NEW YORK - Drugmaker Eli Lilly and Co. raised its adjusted profit forecast Thursday, although its results will include a large legal charge.

Eli Lilly (nyse: LLY - news - people) said it expects adjusted earnings between $3.97 and $4.02 per share in 2008, up from $3.85 to $4 per share. That excludes a charge of $1.48 billion, or $1.33 per share, which Lilly expects to pay to resolve an investigation into the market of its biggest-selling drug, the anti-psychotic Zyprexa. (...)

Lilly takes $1.4 B charge related to investigation
forbes.com 21.10.2008 (Associated Press)
INDIANAPOLIS - Drug maker Eli Lilly and Co. says it will take a $1.42 billion charge in the third quarter related to an investigation into marketing practices for the anti-psychotic Zyprexa.

The company says it is in advanced discussions to settle the investigation.
The investigation was led led by the U.S. Attorney's Office for the Eastern District of Pennsylvania. Lilly says the U.S. attorney's office launched its investigation in 2004.

The charge amounts to $1.29 per share. (...)

Eli Lilly settles Zyprexa inquiries in 32 states (Eli Lilly betaler etter Zyprexa-granskninger i 32 stater)
forbes.com 7.10.2008
NEW YORK - Eli Lilly & Co. said Tuesday it will pay $62 million to resolve investigations into the marketing and promotion of its antipsychotic drug Zyprexa in 32 states and Washington, D.C.

The payments will be divided between the states that were investigating the company, and Lilly said it will take a related charge of 4 cents per share in the third quarter. Zyprexa, the company's top-selling drug with 2007 sales of $4.8 billion, will continue to be available through Medicare programs in all states, and Lilly said there was no finding it had broken any laws.

The company also agreed to provide the states' attorneys general with information about the compensation it paid to health care professionals who received more than $100 per year for promotional speaking or consulting regarding Zyprexa, and agreed to other promotional terms. (...)

Lilly paid $15 million to settle a lawsuit with the state of Alaska in March, and since 2005, the company says it has settled approximately 31,000 individual product liability suits related to the drug's side effects. Those side effects include neuroleptic malignant syndrome and hyperglycemia. (...)

(Anm: Neuroleptic malignant syndrome and delirious mania as malignant catatonia in autism: prompt relief with electroconvulsive therapy.Acta Psychiatr Scand. 2015 Oct;132(4):319-320. Epub 2015 May 28.).)

Psykofarmaka till dementa under lupp
lakemedelsvarlden.se 10.9.2008
Läkemedelsverket kommer inom de kommande veckorna presentera en ny vägledning kring hur antipsykotika läkemedel ska användas, eller inte användas, hos dementa. Dokumentet är ett resultat av en workshop i våras. (...)

Judge to Unseal Documents on the Eli Lilly Drug Zyprexa
nytimes.com 5.9.2008
A federal judge in Brooklyn decided on Friday to unseal confidential materials about Eli Lilly’s top-selling antipsychotic drug Zyprexa, citing “the health of hundreds of thousands of people” and “fundamental questions” about the way drugs are approved for new uses.

The decision by Judge Jack B. Weinstein of Federal District Court came as part of a ruling that gave class-action status to a case brought by insurance companies, pension funds and unions that want Lilly to repay them billions of dollars they spent on the drug. They contend that Lilly hid the side effects of the drug and marketed it for unapproved uses. (...)

Some drugs risky for seniors, FDA says (Noen legemidler er risikable for eldre, ifølge FDA)
seattletimes.nwsource.com 17.6.2008
The Food and Drug Administration warned doctors Monday that prescribing a certain group of psychiatric drugs to seniors suffering from dementia... (...)

The FDA's announcement was an update to a 2005 action, when regulators added warnings about increased heart attacks and pneumonia to drugs called atypical antipsychotics. The medicines include blockbusters like Eli Lilly's Zyprexa and Johnson & Johnson's Risperdal.

FDA said Monday those same risks apply to 11 older drugs known as typical antipsychotics, including Pfizer's Navane and Endo Pharmaceutical's Moban. The drugs were developed in the 1950s and have largely been replaced by the newer medications, which are believed to have fewer side effects, such as tremors. (...)

New schizophrenia drugs no better, Dutch team find (Nye schizofreni-legemidler ikke bedre, ifølge Nederlandske forskere)
reuters.com 29.3.2008
LONDON (Reuters) - Costly new antipsychotic drugs are not significantly better than cheaper older ones at treating a first episode of schizophrenia, Dutch researchers said on Friday.

The finding adds to controversy about the benefits of second-generation products like AstraZeneca Plc's Seroquel and Eli Lilly and Co's Zyprexa, which were introduced in the 1990s and are now multibillion-dollar sellers. (...)

Lilly agrees to $15 million payout to settle Alaskan Zyprexa case
pharmatimes.com 26.3.2008
26 March 2008
US drug giant Eli Lilly has agreed to pay the state of Alaska $15 million to settle claims that its Medicaid programme was not adequately warned over potential side effects from the use of its antipsychotic Zyprexa. (...)

Lilly Settles Alaska Suit Over Zyprexa
forbes.com 26.3.2008
NEW YORK - Eli Lilly and Co. and Alaska announced a $15 million settlement Wednesday in the state's lawsuit over the use of the drug Zyprexa in its Medicaid program.

The deal ensures that Alaska will be treated as well as any other state that may settle with Lilly over similar claims involving the drug, which is used to treat schizophrenia and bipolar disorder.

The agreement included no admission of wrongdoing by Lilly. (...)

Side-Effect Concerns Derail Schizophrenia -Drug Approval (Bekymringer for sideeffekter forpurrer godkjenning av schizofreni-legemiddel)
Psychiatr News 2008;43(6):19 (March 21) (© 2008 American Psychiatric Association)
The FDA issues a not-approvable letter for long-acting olanzapine injection for schizophrenia treatment out of concerns about an unpredictable, and potentially serious, side effect. (...)

Of the 24 patients who had cases of excessive sedation, 20 were hospitalized or visited an emergency department. Five reported temporary loss of consciousness, including three who could not be aroused for a period of time. One of these patients was clinically diagnosed with coma, and another with "symptoms consistent with coma." Two patients were intubated. All patients recovered, and 12 continued to receive additional olanzapine pamoate injections, company representatives said. (...)

(Anm: olanzapine; omsettes under handelsnavnet Zyprexa.)

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. (...)

API patients on Zyprexa got diabetes, official says
adn.com 13.3.2008
TRIAL: Medical director testifies risks weren't fully known. (...)

Lilly Waited Too Long to Warn About Schizophrenia Drug, Doctor Testifies (Lilly ventet for lenge med advarsel om schizofreni-legemiddel, ifølge leges vitnesbyrd)
nytimes.com 8.3.2008
ANCHORAGE — Eli Lilly, the drug maker, could and should have warned physicians as early as 1998 about the link between Zyprexa, its best-selling schizophrenia medicine, and diabetes, an expert witness told jurors Friday in a lawsuit that claims that Zyprexa has caused many mentally ill people to develop diabetes.

Instead, Lilly hid Zyprexa’s risks from doctors to protect the drug’s sales, according to the witness, Dr. John Gueriguian. Lilly waited until 2007 to add strong warnings to Zyprexa’s label to reflect the drug’s tendency to cause severe weight gain and blood sugar changes.

Lilly setter "profitt foran forbrukerens anliggende", sa Dr. Gueriguian på slutten av sitt fire timers vitnemål. (...) (Lilly put “profit over concern of the consumer,” Dr. Gueriguian said Friday near the end of four hours of testimony.)

State: No Alerts on Zyprexa Side Effects
forbes.com 6.3.2008
ANCHORAGE, ALASKA - Eli Lilly and Co. failed to adequately warn doctors and patients of dangerous side effects associated with its drug Zyprexa, an attorney for Alaska said Wednesday in opening arguments in the state's lawsuit against the drug maker.

Lilly did not adequately disclose that using the drug, prescribed to treat schizophrenia and bipolar disorder, could lead to severe obesity, elevated blood sugar and diabetes, lawyer Scott Allen said.

"If they put a warning on this product, their sales would fall," Allen said. "They would lose money. People would choose another drug, and they decided not to disclose what they knew." (...)

FDA Wants More Info on Zyprexa Injection (FDA ønsker mer info på Zyprexa-injeksjon)
forbes.com 28.2.2008
INDIANAPOLIS - The Food and Drug Adminstration won't approve Eli Lilly and Co.'s Zyprexa long-acting injection for adult schizophrenia until the company produces more information about the risks and cause of the excessive sedation seen in certain patients, Eli Lilly said Thursday. (...)

FDA panel supports long-acting Zyprexa
pharmatimes.com 7.2.2008
A US Food and Drug Administration Advisory Committee has supported the approval of a long-acting form of Eli Lilly’s antipsychotic Zyprexa, despite concerns over excessive sedation side effects in some patients. (...)

FDA staff cite safety concern with Lilly drug
reuters.com 4.2.2008
WASHINGTON (Reuters) - Excessive sedation is a "serious safety concern" with an experimental, long-acting form of Eli Lilly and Co's blockbuster Zyprexa schizophrenia drug, U.S. drug reviewers said in an analysis released on Monday. (...)

Lilly in Settlement Talks With U.S.
nytimes.com 30.1.2008
Eli Lilly and federal prosecutors are discussing a settlement of a civil and criminal investigation into the company’s marketing of the antipsychotic drug Zyprexa that could result in Lilly’s paying more than $1 billion to federal and state governments. (...)

Zyprexa: Suicide can be a Side Effect of Drugs
lawyersandsettlements.com 10.1.2008
Washington, DC: The news is getting harder and harder to ignore. More drugs are being linked to an increased risk of violence and suicide. While some people would argue that, at least in the case of Zyprexa, it is the underlying condition of the patient that increases the risk of suicide, there are more drugs being linked to this risk, making it more difficult to deny that medications can cause people to commit suicidal acts. (...)

FDA to Meet on Long-Lasting Zyprexa
forbes.com 8.1.2008
WASHINGTON - The Food and Drug Administration has scheduled a meeting next month to review the safety and effectiveness of a long-acting version of Eli Lilly & Co.'s schizophrenia drug. (...)

FDA said it is particularly concerned about incidents of severe drowsiness among patients tested with the new formulation.

Zyprexa is currently available in pill form to treat schizophrenia and bipolar disorder. Sales grew 6 percent to $1.67 billion in the final quarter of last year.

Shares of Eli Lilly & Co. rose $1.03 to $55.57 in morning trading Tuesday. (...)

A risky drug may get wider market
sptimes.com 16.12.2007
The FDA may approve Zyprexa for kids, despite its significant side effects in adult use

It sounds like a cosmic, FDA joke:

The Food and Drug Administration approves the antipsychotic drug Zyprexa to treat adults with schizophrenia or bipolar disorder. It becomes a market wonder, a bestseller. But the side effects turn out to be dangerous; some patients develop diabetes.

Some 30,000 people sue the manufacturer, Eli Lilly. The pharmaceutical giant shells out more than $1-billion to settle the cases.

Here comes the punch line:

Though studies show that kids are even more susceptible to Zyprexa's dangerous side effects, now Lilly wants the government's seal of approval for adolescents to use it. And the FDA is about to say yes. (...)

Eli Lilly Putting Zyprexa Patients At Risk of Suicide
lawyersandsettlements.com 25.11.2007
Rockville, MD: Now we know there is a corelleation between Zyprexa and suicide, people who may not have realized that their suicidal thoughts were related to Zyprexa, now understand that they may not have been in control of their thoughts and actions at all. Unfortunately, some patients, including youth, have committed suicide while taking this medication and even though their families can file lawsuits against Eli Lilly, nothing will bring these victims back.

One website, [psychdrugdangers.com] makes available the FDA's Adverse Event Reporting System. The website claims to have a listing of Adverse Event Reports made "between 2004 and 2006 where the listed psychiatric drug was identified as the Primary Suspect Drug responsible for causing these reactions." If this website is accurate, the number of suicides and suicide attempts by people who were taking Zyprexa is alarming and is not something that should not be ignored. (...)

Doctor Who Leaked Documents Will Pay $100,000 to Lilly
nytimes.com 30.10.2007
A doctor who leaked confidential materials about Eli Lilly’s antipsychotic drug Zyprexa agreed yesterday to settle a legal dispute with Lilly over the documents. (...)

Dr. Egilman acknowledged that Lilly had a different view of the safety of its schizophrenia drug Zyprexa than was portrayed in the documents. He did not admit that he accepted Lilly’s view that Zyprexa was safe. (...)

Läkemedel kan orsaka ”livsstilssjukdomar”
lakemedelsvarlden.se 22.10.2007
(...) Stephan Rössner nämnde särskilt psykofarmaka som orsak till övervikt. Han berättade att han möter unga flickor som tagits in för graviditetspsykos och kommer ut botade från sina psykiska besvär men 30 kilo tyngre. (...)

Givetvis ska patienter som verkligen lider av schizofreni få dessa läkemedel, men problemet är att preparaten ibland förskrivs utanför indikation och alldeles för lättvindigt. I Uppdrag Granskning framgick att Zyprexa (ett av de psykofarmaka som orsakar mest viktuppgång) försäljs för omkring 250 miljoner kronor varje år i Sverige. Detta fast läkemedlet enbart är godkänt för behandling av schizofreni och bipolär sjukdom. (...)

Patients Come Forward With Zyprexa Suicide Complaints
lawyersandsettlements.com 20.10.2007
Boise, ID: Since LawyersandSettlements began posting about the link between [Zyprexa and suicide], we have received many emails from frustrated patients who say taking Zyprexa completely altered their personality and resulted in suicide attempts. We have also heard from family members of patients who committed suicide. These family members all say that their loved ones changed drastically for the worse after they started taking Zyprexa. (...)

Studies have also shown that Zyprexa is more expensive, but not more effective, than older drugs that were used to treat schizophrenia. Furthermore, a study published in the November 2007 issue of the Journal of Affective Disorders found an increase in suicidal behavior in bipolar patients who took antipsychotic medications. (...)

Lilly Adds Strong Warning Label to Zyprexa, a Schizophrenia Drug
nytimes.com 13.10.2007
Eli Lilly yesterday added strong warnings to the label of Zyprexa, its best-selling medicine for schizophrenia, citing the drug’s tendency to cause weight gain, high blood sugar, high cholesterol and other metabolic problems. (...)

Concern about Zyprexa’s side effects has been increasing since at least 2004, and Zyprexa’s prescriptions and market share have fallen sharply over the period. (...)

Ms. Lemons also noted that older antipsychotic medicines also have severe side effects, including a tendency to cause facial tics.

The new warnings may add to the controversy surrounding Zyprexa, which is by far Lilly’s best-selling drug. (...)

Internal Lilly documents disclosed by The New York Times last December indicated that Lilly was aware of Zyprexa’s tendency to cause weight gain and blood sugar changes by the late 1990s but played down the risks. (...)

Lilly has spent $1.2 billion since 2004 to settle lawsuits from 28,500 people who claimed they developed diabetes or heart problems after taking the drug. At least 1,200 more lawsuits are still pending. (...)

Zyprexa To Win FDA Approval For Teens
pharmalot.com 26.9.2007
September 26th, 2007 7:39 am By Ed Silverman
That’s right. And it’s likely to occur because a senior FDA official overruled his colleagues. A three-member FDA team of medical reviewers initially urged rejecting Zyprexa for pediatric use because of inconsistent data from studies in US and Russian teens, Bloomberg News reports. But in an April 29 memo posted on the FDA’s Web site (look here), Thomas Laughren, head of the agency’s psychiatry division, wrote that the drug’s benefits in some studies outweighed the reviewers’ concerns.

Zyprexa, with $4.4 billion in global sales in 2006, is Lilly’s biggest seller and the biggest among five antipsychotics. But the teen market is important to Lilly, because Zyprexa’s market share has slipped as 86 percent of psychiatrists are writing fewer scrips due to side effects - weight gain and diabetes. Johnson & Johnson’s Risperdal last month became the only drug in the class cleared for pediatric use though docs have long prescribed the pills to children.

A growing number of states, meanwhile, are suing Lilly over improperly marketing Zyprexa. Their argument - downplaying or hiding side effect data while state Medicaid programs fork over big money for the med. (...)

Lilly's Zyprexa Poised for Approval for U.S. Teens (Update3)
bloomberg.com 26.9.2007
Sept. 26 (Bloomberg) -- Eli Lilly & Co.'s best-selling schizophrenia drug Zyprexa is poised to get U.S. approval for treating adolescents diagnosed with mental illness after a senior government regulator overruled his colleagues. (...)

Almost 44 percent of teenagers taking Zyprexa gained more than 7 percent of their body weight, compared with 7 percent of those on placebos, according to Laughren. Levels of fats, blood sugar and the hormone prolactin increased in patients taking Zyprexa, while dropping in placebo patients.

"A 7 percent increase in body weight in a young patient in such a short time may predispose people to diabetes and create a cardiac burden as the heart is forced to work harder,'' Klotz said."

Ark.: Lawsuit Over Drug Marketing
forbes.com 24.9.2007
LITTLE ROCK - A Houston-based private law firm will pursue a suit seeking millions of dollars for Arkansas' Medicaid program from Eli Lilly and Co. and two other drug companies accused of improperly marketing anti-psychosis drugs.
Attorney General Dustin McDaniel has told state legislators that the suit would seek recovery of money paid by the state's Medicaid program for anti-psychosis drugs prescribed for uses not approved by federal regulators or indicated in labeling. (...)

Zyprexa Linked to Suicide Risk
lawyersandsettlements.com 17.9.2007
Houston, TX: Zyprexa, an atypical antipsychotic drug, has been linked to an increased risk of suicide acts. Clinical trials for Zyprexa have found that patients taking the drug are more likely to commit suicide than patients on any other antipsychotic medication. Lawsuits are now being filed against the maker of Zyprexa, alleging the company knew about the risk of suicidality but failed to warn physicians or the public about that risk.

Patients taking Zyprexa have reported increased adverse reactions to the drug, including agitation, sleep disturbances and akathisia (a condition that involves inner restlessness, agitation and emotional trauma). Akathisia has been linked to suicide and homicide and is a common adverse side effect of antipsychotic drugs. In fact, both sleep disturbances and akathisia are precursors to suicide.

Dr. David Healy, a Professor of Psychiatry at the University of North Wales, noted, "The studies in adults with Zyprexa that Lilly submitted to the FDA demonstrate, as far as I can establish, a higher death rate on Zyprexa than on any other antipsychotic ever recorded."

Lawsuits have been filed against Eli Lilly & Company, makers of Zyprexa, alleging that the antipsychotic has caused people to commit, or attempt to commit, suicide. One such case, known as Ebel vs. Eli Lilly & Company, was filed in Texas. (...)

Eli Lilly Settles Zyprexa Lawsuit; Attempts to Shift Blame to Legal Advertising
newsinferno.com 19.6.2007
Eli Lilly, the makers of Zyprexa announced it had settled another 900 lawsuits against its anti-psychotic medication Zyprexa, on that very same day Eli Lilly was claiming that legal advertisements where hurting patients. The company asserts that a recent study showed that patients using Zyprexa were more likely to abruptly stop taking it once they were exposed to legal advertising highlighting its harmful side effects. The study, which Eli Lilly paid for, surveyed only 402 patients – a small number considering that an estimated 2 million people may be using Zyprexa. (...)

Eli Lilly: Drug Ads Influencing Patients
forbes.com 13.6.2007
Eli Lilly and Co., which has faced thousands of lawsuits over its anti-psychotic Zyprexa, says lawyers' ads about the drug are prompting some patients to stop taking mental illness medications when they shouldn't. (...)

Lilly Settles Zyprexa Lawsuits (Lilly inngår forlik i Zyprexa-søksmål)
forbes.com 12.6.2007
Eli Lilly and Co. settled an additional 900 product liability lawsuits involving its top-selling drug, the anti-psychotic Zyprexa.

The Indianapolis-based drug maker declined to release the settlement amount. But spokeswoman Marni Lemons said Tuesday it would have no material impact on the company's financial statements.

Lilly has settled roughly 28,500 product liability claims involving Zyprexa over the past two years. In June 2005, the company settled 8,000 claims for $690 million. This past January, it settled more than 18,000 for roughly $500 million. (...)

U.S. Wonders if Drug Data Was Accurate (Amerikanske myndigheter stiller spørsmål om legemiddeldata var korrekte)
nytimes.com 25.4.2007
The Food and Drug Administration is examining whether Eli Lilly & Company provided it with accurate data about the side effects of the antipsychotic drug Zyprexa, a potent medicine that has been linked to weight gain and diabetes.

Zyprexa is Lilly’s top-selling drug, with $4 billion in annual sales.

The F.D.A. has questions about a Lilly document from February 2000 in which the company found that patients taking Zyprexa in clinical trials were three and a half times as likely to develop high blood sugar as those who did not take the drug.

That document was not submitted to the agency. But a few months later, Lilly provided data to the F.D.A. that showed almost no difference in blood sugar between patients who took Zyprexa and those who did not.
The F.D.A. confirmed its inquiry in response to questions from The New York Times. The agency said it had not yet decided whether to take any action against Lilly. (...)

Medisiner kan utløse ulvehunger
bladet.psykiskhelse.no 28.3.2007
Vanlige medisiner mot alvorlige psykiske lidelser kan gi økt appetitt, kraftig vektøkning og diabetes. – Jeg synes problemet med vektøkning blant psykisk syke er blitt større de siste årene, sier fagkonsulent Svein Einarsbøl i Asker kommune. (...)

De vanligste medisinene mot alvorlige psykiske lidelser kan medføre en stadig sultfølelse og dermed kraftig vektøkning. Noen medisiner gir også økt risiko for type 2 diabetes. Særlig er dette en bivirkning av noen av de nye legemidlene mot psykose, de såkalte atypiske antipsykotiske legemidlene. Denne vektøkningen kommer på toppen av de vanlige livsstilsproblemene som «annenhver nordmann» sliter med. De som har psykiske lidelser, kan derfor få dobbel belastning. (...)

Senator Probes Eli Lilly Drug Promotion (Senator gransker Eli Lillys markedsføring av legemiddel)
forbes.com 5.4.2007
Republican Sen. Charles Grassley has requested documents from Eli Lilly in the wake of lawsuits alleging the company downplayed risks and wrongly promoted its top-selling drug Zyprexa.

In a letter released late Wednesday, the Iowa lawmaker asks Lilly to provide "e-mails, letters, reports" and other internal documents relating to Zyprexa, which is approved to treat schizophrenia and bipolar disorder. Grassley is the ranking member of the Senate Finance Committee.

Indiana-based Lilly said Thursday it will cooperate with the request from the Iowa lawmaker. (...)

(Anm: Sen. Chuck Grassley. GRASSLEY SEEKS MARKETING AND SAFETY DOCUMENTS FROM MAJOR DRUG MAKER. grassley.senate.gov 4.4.2007.)

New York Times Examines Eli Lilly Program Aimed at Reducing Unnecessary Medicaid Prescriptions for Antipsychotic Drug Zyprexa
kaisernetwork.org 23.3.2007
The New York Times on Friday examined an Eli Lilly program that offers state Medicaid programs assistance in monitoring physicians' prescribing practices for Zyprexa, a treatment for schizophrenia and bipolar disorder that is the single largest drug cost in state Medicaid budgets. Under the program, which Lilly has implemented in two dozen states since 2003, the company pays New York-based Comprehensive NeuroScience an undisclosed amount to monitor physicians' prescribing practices. (...)

In Some States, Maker Oversees Use of Its Drug
nytimes.com 23.3.2007
Many states, looking to rein in the cost of expensive antipsychotic drugs like Zyprexa, have turned to an unusual ally for help — the very company that sells the drug.

At more than $300 for a monthly prescription, Zyprexa, which is used to treat schizophrenia and bipolar disorder, is the single biggest drug cost for state Medicaid budgets.

So Eli Lilly, the maker of Zyprexa, offers to help states monitor doctors who treat Medicaid patients to make sure they are not wasting money on mental illness drugs because of what psychiatrists call “sloppy prescribing” — giving patients too many similar medications or doses that are too high. Twenty states use Lilly’s free service. (...)

Lilly wins court case to get leaked Zyprexa documents back
pharmatimes.com 15.2.2007
Eli Lilly's battle to defend its actions concerning Zyprexa has taken yet another turn with the news that a US federal judge has ordered several individuals to orders return confidential papers leaked to the media about the blockbuster antipsychotic.

(…) Whistleblower slams FDA over handling of Zyprexa
Lilly may have won a victory over Zyprexa in the courts but the drug found itself once again at the centre of attention in the US Congress. Dr David Graham, the US Food and Drug Administration official who caused a stir over the last couple of years by criticising the agency's handling of Merck & Co's withdrawn painkiller Vioxx (rofecoxib), told a congressional hearing that the FDA acted far too slowly in changing the label on Zyprexa to include the weight gain/diabetes risk. The famous whistleblower also told the hearing that other antipsychotic medications also warrant closer scrutiny. (...)

Judge Rules Drug Documents Must Be Returned to Eli Lilly
nytimes.com 14.2.2007
A federal district judge in Brooklyn ruled yesterday that confidential marketing materials belonging to Eli Lilly & Company about its top-selling anti-psychotic drug Zyprexa must be returned to the company by a doctor and a lawyer who, the judge said, engaged in a scheme to leak them to the news media. (...)

Researchers discover why antipsychotics cause weight gain
pharmatimes.com 15.2.2007
Scientists at a prestigious US medical institute believe that they have uncovered the reasons why antipsychotic drugs cause patients to gain so much weight that they often develop life-threatening complications such as diabetes and heart disease.

Professor Solomon Snyder of the Johns Hopkins School of Medicine and one of the authors of the study, which will be published online next week at the Proceedings of the National Academy of Sciences, said: "We have now connected a whole class of antipsychotics to natural brain chemicals that trigger appetite." (...)

Eli Lilly Profit Falls But Still Beats Expectations
forbes.com 31.1.2007
Cash-draining litigation and plant closings drove down Eli Lilly’s fourth-quarter profit, but plenty of pill poppers still sought out the drug-maker’s products and helped the company beat expectations. (...)

Ny ekonomisk uppgörelse kring Zyprexa
Läkemedelsvärlden 2006(1-2) (FEBRUARI 2007)
Arton tusen personer får dela på femhundra miljoner dollar. Det blev resultatet i den senaste uppgörelsen mellan läkemedelsföretaget Eli Lilly och patienter som behandlats med Zyprexa. (...)

Lilly investigated in US over the marketing of olanzapine (Lilly granskes i USA grunnet sin markedsføring av olanzapine (Zyprexa))
BMJ 2007;334:171 (27 January) (British Medical Journal)
The multinational drug company Eli Lilly faces the threat of lawsuits from US state governments over alleged illegal practices in the marketing of its drug olanzapine (Zyprexa), which is used to treat schizophrenia and bipolar disorder.

The company has already agreed to settle more than 18 000 outstanding product liability claims that relate to the drug in the United States for an undisclosed sum. (...)

The states are investigating claims that the company concealed data that show serious risk of side effects including weight gain, hyperglycaemia, and diabetes. (...)

Eli Lilly was concerned by Zyprexa side-effects from 1998 (Eli Lillys var bekymret over bivirkninger ved Zyprexa siden 1998)
business.timesonline.co.uk 23.1.2007
Eli Lilly, the American pharmaceutical giant that has consistently denied any link between Zyprexa, its antipsychotic drug, and diabetes, was concerned about the side-effects of the drug as early as 1998, according to documents seen by The Times. (...)

States Study Marketing of Lilly Pill (Stater gransker markedsføring av Lilly-pille)
nytimes.com 20.1.2007
Stepping up government investigations into Eli Lilly’s marketing of its best-selling drug Zyprexa, state prosecutors in Illinois and Vermont have demanded that the company turn over information about the way it promoted the medication.

On Thursday, lawyers from the consumer protection division of the Illinois attorney general’s office demanded that Lilly hand over marketing materials, e-mail messages, and other documents with information about promotion of Zyprexa. Vermont investigators issued a similar order yesterday morning.
The orders are the civil equivalents of criminal subpoenas, according to Deborah Hagan, the chief of the Illinois consumer protection division. (...)

Documents Borne by Winds of Free Speech
heraldtribune.com 15.1.2007
(...) It is a messy plot that pits Eli Lilly, the pharmaceutical giant at the center of several articles in The New York Times suggesting that the company tried to hide or play down the health risks of its leading antipsychotic drug, Zyprexa, and lawyers representing various individuals, organizations and Web sites — all arguing that their online speech has been gagged. (...)

Drug company seeks to suppress internal memos (Legemiddelfirma forsøker å hemmeligholde interne notater)
BMJ 2007;334:59 (13 January) (British medical Journal)
The drug maker Eli Lilly instigated legal action against a number of doctors, lawyers, journalists, and activists over hundreds of internal corporate documents and emails said to have been obtained by them regarding the antipsychotic drug olanzapine (Zyprexa). Eli Lilly obtained a court injunction on 29 December ordering 16 individuals and organisations to stop publishing the documents and to remove any copies posted on the internet. (...)

DRUG MAKER SETTLES 18,000 ZYPREXA CLAIMS
INDYSTAR.COM 5.1.2007
Lilly's top moneymaker has also been a big headache
Indy-based firm will have paid more than $1 billion to resolve suits over antipsychotic medication

Facing the prospect of lengthy trials and unfavorable publicity, Eli Lilly and Co. on Thursday put behind it thousands more legal claims over its best-selling drug, Zyprexa. (...)

Lilly Settles With 18,000 Over Zyprexa
nytimes.com 5.1.2007
Eli Lilly agreed yesterday to pay up to $500 million to settle 18,000 lawsuits from people who claimed they had developed diabetes or other diseases after taking Zyprexa, Lilly’s drug for schizophrenia and bipolar disorder. (...)

Criminal Prosecution of Lilly Sought Over Zyprexa (Lilly best tiltalt for Zyprexa)
by Evelyn Pringle
opednews.com 4.1.2007
California Attorney, Ted Chabasinski, is calling for the criminal prosecution of Eli Lilly executives for hiding the adverse effects of Zyprexa, based in part on articles last month in the New York Times which quote internal company documents that revealed that Lilly knew about the adverse effects for a decade but kept the information hidden. (...)

Mother Wonders if Psychosis Drug Helped Kill Son
ytimes.com 4.1.2006
At first, the psychiatric drug Zyprexa may have saved John Eric Kauffman’s life, rescuing him from his hallucinations and other symptoms of acute psychosis. (...)

For many patients, the side effects of Zyprexa are severe. (...)

Exactly how many people have died as a result of Zyprexa’s side effects, and whether Lilly adequately disclosed those risks, are central issues in the thousands of product-liability lawsuits pending against the company, and in state and federal investigations. (...)

Eli Lilly now faces federal and state investigations about the way it marketed Zyprexa. Last week — after articles in The Times about the Zyprexa documents — Australian drug regulators ordered Lilly to provide more information about what it knew, and when, about Zyprexa’s side effects. (...)

Eli Lilly to Settle More Zyprexa Suits
forbes.com 4.1.2006
Drug maker Eli Lilly and Co. said Thursday it will settle more liability lawsuits for its anti-psychotic medication Zyprexa for less than $500 million.
The settlement covers more than 18,000 claims that the company did not adequately warn patients taking the medication of a heightened diabetes risk. The company did not disclose the exact dollar amount of the new settlement. About 1,200 claims are still outstanding.

In June 2005, Lilly settled more than 8,000 similar claims for a little less than $700 million.

Lilly will record a settlement charge in the fourth quarter. Analysts surveyed by Thomson Financial expect fourth-quarter earnings per share of 82 cents. (...)

New York Times kräver kongressförhör om Zyprexa
Läkemedelsvärlden 2006(12) (Desember)
Efter avslöjanden i en rad artiklar kräver New York Times på ledarplats att kongressförhör ska inledas med anledning av företaget Lillys marknadsföring av schizofreniläkemedlet olanzapin (Zyprexa). (...)

Court Orders Lawyer to Return Documents About an Eli Lilly Drug
nytimes.com 20.12.2006
A federal court in Brooklyn overseeing product liability lawsuits against Eli Lilly’s best-selling drug Zyprexa has ordered the lawyer who provided company documents to The New York Times and other organizations and individuals to return the documents. (...)

Eli Lilly Said to Play Down Risk of Top Pill (Eli Lilly hevdes å ha tonet ned risiko for bestselgende pille)
nytimes.com 17.12.2006 (New York Times)
The drug maker Eli Lilly has engaged in a decade-long effort to play down the health risks of Zyprexa, its best-selling medication for schizophrenia, according to hundreds of internal Lilly documents and e-mail messages among top company managers.

Dokumenter overlevert Times av advokat som representerer pasienter, viser at lederne i Lilly holdt tilbake informasjon for leger om Zyprexas link til fedme og tilbøyelighet til å øke blodsukker - begge kjente for risikofaktorer for diabetes. (The documents, given to The Times by a lawyer representing mentally ill patients, show that Lilly executives kept important information from doctors about Zyprexa’s links to obesity and its tendency to raise blood sugar — both known risk factors for diabetes.)

Lilly’s own published data, which it told its sales representatives to play down in conversations with doctors, has shown that 30 percent of patients taking Zyprexa gain 22 pounds or more after a year on the drug, and some patients have reported gaining 100 pounds or more. But Lilly was concerned that Zyprexa’s sales would be hurt if the company was more forthright about the fact that the drug might cause unmanageable weight gain or diabetes, according to the documents, which cover the period 1995 to 2004.

Zyprexa has become by far Lilly’s best-selling product, with sales of $4.2 billion last year, when about two million people worldwide took the drug. (...)

Documents suggest Lilly concealed drug's risks (Dokumenter tyder på at Lilly hemmeligholdt risiko ved legemiddel)
seattletimes.nwsource.com 17.12.2006
The drug maker Eli Lilly has engaged in a 10-year effort to downplay the health risks of Zyprexa, its best-selling medication for schizophrenia, according to hundreds of internal Lilly documents and e-mails among top company managers. (...)

Lilly has consistently denied such a link and did so again Friday in a written response to questions about the documents. The company defended Zyprexa's safety and said the documents had been taken out of context. (...)

Lillys dementi saknar tyngd”
Läkemedelsvärlden (November 2005)
DEBATT
Inte oväntat bemöter Eli Lilly min kommentar om Zyprexa i Nils Bergeås intervju (LMV 11/05), men insändaren gör också ett anmärkningsvärt påstående. Jag refererade till dokumentation om allvarliga biverkningar undanhållna av det amerikanska huvudkontoret, som en advokat (också läkare) tagit del av i ett rättsfall. Jag har svårt att tro att det svenska kontoret haft tillgång till hemliga dokument från USA.

Dementin fran Eli Lilly Sweden AB saknar tyngd eftersom den inte bekräftat att anställda på dotterbolaget är insatta i frågan.

Mörkning av negativ information om marknadsförda läkemedel är tyvärr vanlig. Sanningen kommer oftast inte fram förrän fallen går till domstol. Endast i undantagsfall diskuteras de i medicinska tidskrifter. Vi rapporterade till exempel om Bayer och cerivastatin (Lipobay) förra året (1).

En stor jämförande studie av Zyprexa och andra atypiska antipsykotika vid schizofreni (CATIE, 2005) rapporterade nyligen att tre av fyra patienter avbröt behandlingen i förtid, främst på grund av bristande effekt eller biverkningar. För Zyprexa avbröts behandlingen i 64 procent av fallen. Detta ger inget kraftfullt stöd för Zyprexas "effekt och säkerhet"!

Mest häpnadsväckande för mig i Eli Lillys inlägg är påståendet att Zyprexa är "ett läkemedel som räddar liv". Var finns dokumentationen för att Zyprexa förbättrar överlevnaden? Kanske något för NBL att ta ställning till.

Jag välkomnar Läkemedelsindustriföreningens agerande. Dess kursändring är det första steget mot bättre öppenhet rörande läkemedelsbiverkningar och säkerhetsutvärdering. Tyvärr är erfarenheten att frivilliga åtaganden oftast är relativt effektlösa. Vad som saknas, det andra steget, är att brott mot dessa principer får allvarliga konsekvenser – indragning av läkemedel, höga böter och i värsta fall fängelse.

I USA finns för närvarande lagförslag i kongressen som omfattar dessa typer av straff. Om Lif och dess systerorganisationer i Europa är ovilliga att ta det andra steget, är risken att deras agerande faller under rubriken "lip service".

Curt Furberg
Professor, Wake Forest University, USA

”Lilly döljer negativ information om Zyprexa”
Läkemedelsvärlden (November 2005)
Curt Furberg kräver större ärlighet från läkemedelsindustrin

Enligt Curt Furberg försvinner läkemedelsföretagens etiska tänkande så fort ett läkemedel blir storsäljare – då har man inte råd att vara öppna med negativa studieresultat och biverkningsrapporter. Företagen lovar också rutinmässigt inför godkännanden att genomföra uppföljningsstudier – som sedan sällan blir av. (...)

– Det jag reagerar på är att många tror att det här bara gäller Merck och Vioxx. Men det enda nya här är att vi fått en öppen diskussion i media efter indragningen. Men det finns i själva verket värre exempel, exempelvis Zyprexa.

– Det stora problemet är att industrin känner till biverkningar som inte rapporteras till FDA, inte till läkarkåren, inte till patienterna. (...)

– Det jag reagerar på är att många tror att det här bara gäller Merck och Vioxx. Men det enda nya här är att vi fått en öppen diskussion i media efter indragningen. Men det finns i själva verket värre exempel, exempelvis Zyprexa.

– Det stora problemet är att industrin känner till biverkningar som inte rapporteras till FDA, inte till läkarkåren, inte till patienterna.

Hur vet du det?

– Jag har suttit som expertvittne i flera rättsfall. Då släpps all intern dokumentation så att vittnena kan ta del av den. Det har bland annat gällt i rättegångar om cerivastatin (Lipobay) som försvann från marknaden, och Warner Lamberts diabetesmedel troglitazon (Rezulin), där interna dokument tidigt visat att läkemedlen hade fler biverkningar än vad alla utomstående visste.

Menar du att Zyprexa kan bli ”nästa Vioxx”?

– Allvarliga former av diabetes och kraftig viktökning har rapporterats. Ett rättsfall var på gång med Zyprexa och jag blev inkopplad, fick ta del av information och talade med en advokat. Han, som var erfaren av liknande fall, berättade att ”det här är värre än allt annat jag sett, det finns ingen chans att företaget kan låta det här gå till domstol, då offentliggörs allting. De måste gå med på en uppgörelse i godo.”

Så blev det också. Man jobbar konsekvent med sådana uppgörelser i USA.

– Problemet är att företagen inte har råd att vara öppna när läkemedel kommit ut på marknaden och säljer mycket. Man undanhåller data. Min förhoppning är att företagen under trycket av böter, rättsfall och nya lagar tvingas vara mer öppna.

– Det som är skrämmande är att så länge böterna är lägre än inkomsterna vill man ha kvar ett läkemedel på marknaden. Med ett sådant resonemang ser man inget människovärde.

– Så har åtminstone inte MSD resonerat. Man drog visserligen på Vioxx-beslutet men när studien kom agerade man föredömligt på en gång. Man hade viss intern dokumentation, och kanske borde man dragit in Vioxx tidigare, men det är alltid lätt att säga i efterhand. Merck är alltså inte på något sätt värre än de andra företagen, vilket man kan tro av debatten, kanske till och med tvärtom.

Lilly replikerar: "Felaktigt och oansvarigt om Zyprexa"
Läkemedelsvärlden (November 2005)

Svidande kritik mot Lilly måste bemötas
Lederartikkel. Nils Bergeå, t f chefredaktör
Läkemedelsvärlden (Novemger 2005)
SE ÄVEN ADDENDUM (20051104) NEDANFÖR LEDARTEXTEN

Efter Vioxx-indragningen har läkemedelsindustrins rykte slagit alla bottenrekord. Det gäller inte minst i USA, och situationen är till stor del självförvållad.
Den mest relevanta kritiken mot företagen handlar om mörkning av studieresultat och biverkningsrapporter, ovilja att genomföra uppföljningsstudier som man utfäst sig att verkställa, olika former av studiemygel och publikationsbias till förmån för ”fördelaktiga” studieresultat. Detta har parats med ett i många fall osunt förhållningssätt till kunderna, läkarkåren.

Det tycks vara en bister sanning att företagen, som i fallet med Vioxx, inte ansett sig ha råd att vara öppna om säkerhetsproblem när ett läkemedel blivit en storsäljare. Det nya efter Vioxx är att den amerikanska allmänheten börjat förstå det.

Enligt professor Curt Furberg, som intervjuas i detta nummer, är Zyprexa ett väl så flagrant aktuellt exempel. Lilly vet betydligt mer än vad som är allmänt känt om läkemedlets koppling till allvarliga metabola biverkningar och diabetes, menar han. Uppgörelser med drabbade patienter betingar i tysthet skyhöga belopp i USA, men än så länge är dessa summor lägre än intäkterna och läkemedlet måste därför hållas kvar på marknaden, hävdar Furberg. (...)

Curt Furbergs kritik mot Lilly om Zyprexa, se länk i högermarginalen här intill, är stenhård. Jag har sedan jag genomförde intervjun med honom även tagit del av Lillys syn på saken, och företagets bild av verkligheten är inte oväntat en helt annan.

Är det Furberg gett uttryck för korrekt är det skrämmande och ett tecken på att industrins rörelse mot ökad öppenhet inte kommit så långt som man kan önska. För patienternas skull är förhoppningsvis Lillys version den som bäst överensstämmer med verkligheten. Lilly har gått i första ledet i en föredömlig utveckling mot ökad transparens, och det agerande Curt Furberg beskriver vore helt oförenligt med detta.

I alla händelser lär antagligen ord stå mot ord i frågan om Zyprexa, vilket riskerar leda till en infekterad ordväxling i Läkemedelsvärldens spalter. Lilly har nu replikerat – se länk i högermarginalen – och Curt Furberg har sagt sig vilja föra meningsskiftet vidare.

Kommentar till Lillys replik från Läkemedelsvärlden
Läkemedelsvärlden (November 2005)

Replik från Lif: "Vi menar vad vi säger"
Läkemedelsvärlden (November 2005)

Lilly Profit Rises on Sales of Newer Drugs
New York Times 20.10.2005
INDIANAPOLIS, Oct. 20 (AP) - Eli Lilly & Company said Thursday that its third-quarter profit rose 5 percent on strong sales of newer drugs and diabetes products, which helped offset lackluster growth of its anti-psychotic drug Zyprexa.

Net income grew to $794.4 million, or 73 cents a share, from $755.2 million, or 69 cents a share, a year earlier. Revenue rose 10 percent, to $3.60 billion from $3.28 billion, led by a 13 percent increase in sales of diabetes products to $652.8 million. (...)

Sales of Zyprexa rose 1 percent to $1.04 billion. Zyprexa sales fell 10 percent in the United States but rose 14 percent overseas.

Sales of Lilly's treatment for attention deficit disorder, Strattera, fell 14 percent, to $140.9 million from a year ago. In late September, Lilly announced it was adding a warning to the medication to alert patients that it could cause suicidal thoughts in children taking the drug.

Shares of Lilly, which is based in Indianapolis, fell 35 cents, to close at $51.25.

Study Finds No Best Schizophrenia Drug
Los Angeles Times 19.9.2005
— The nation's leading schizophrenia drug doesn't work much better than an older, far cheaper medicine, says a major government study that found no clear winner in comparing treatments for the devastating mental illness.

The biggest surprise: An overlooked generic drug called perphenazine -- around since the 1950s but seldom used -- proved as effective as all but one of a class of newer treatments called atypical antipsychotics that make up 90 percent of schizophrenia-related prescriptions today. (...)

Government study information: http://www.nimh.nih.gov/healthinformation/catie.cfm

Leading schizophrenia drug no better than older, cheaper kind
USA TODAY 19.9.2005
— The nation's leading schizophrenia treatment doesn't work much better than an older, far cheaper drug, says a government study that is the most comprehensive comparison of therapies for the 3.2 million Americans with the devastating mental illness. (...)

Those taking Eli Lilly & Co.'s Zyprexa did slightly better, staying on the medicine longer before switching and thus experiencing slightly fewer hospitalizations, researchers reported Monday.

However, Zyprexa was far more likely than leading competitors to cause some troubling side effects: severe weight gain associated with high cholesterol, high blood sugar and even Type 2 diabetes.

The big surprise was that older generic drug perphenazine was just as effective as Zyprexa's main competitors — Seroquel, Risperdal and Geodon — and Zyprexa's advantage was modest, the study found.

That is a striking finding, considering that the newer drugs cost more than 10 times as much as perphenazine, used since the 1950s.

"It's simply playing to the bias of jurors ... a certain perception that there are too many lawsuits and that it's causing society problems," Higbee said.

Lilly to pay nearly $700M to settle Zyprexa claims (Lilly betaler nærmere 700 millioner dollar for å forlike krav)
USA TODAY 10.6.2005
INDIANAPOLIS (AP) - Eli Lilly & Co. endret sin preparatomtale for å advare publikum om at deres antipsykotika legemiddel kunne utsette pasienter for risiko for å utvikle diabetes. (Eli Lilly & Co. changed its labels to warn people that its anti-psychosis drug Zyprexa could put patients more at risk for developing diabetes.)

But the warning came after 8,000 people claimed the labels before September 2003 did not tell them of the risk. The company now is prepared to pay nearly $700 million to those people as part of a settlement announced Thursday.

The Indianapolis-based company plans to establish the settlement fund, which will affect its second-quarter earnings. The company said it plans to take a pretax charge of at least $700 million for the fund and to cover other claims not in the agreement.

When the settlement is finalized, it will resolve the majority of Zyprexa claims pending in the United States, according to a Lilly news release Thursday.

However, the agreement only involves people who filed claims arguing that they developed diabetes-related conditions from using Zyprexa, which is used to treat schizophrenia and bipolar disorder. Lilly said it is prepared to continue its "vigorous defense" of the drug in the remaining cases.

"While we believe the claims are without merit, we took this difficult step because we believe it is in the best interest of the company, the patients who depend on this medication, and their doctors," Lilly Chairman and CEO Sidney Taurel said in the statement.

Most of the lawsuits claimed that before September 2003, the information on Zyprexa labels regarding the risk of hyperglycemia and diabetes was not adequately displayed. Hyperglycemia is a condition in which the blood has elevated sugar levels, typical in diabetics.

In September 2003, the FDA required label changes for all atypical anti-psychotic drugs to warn against the risk.

Christopher Seeger, a member of the plaintiffs' steering committee, said the group was pleased with the agreement.

"The patient population to which this drug is given has difficult medical histories," Seeger said. "Protracted litigation was in no one's interest."

In April, Lilly said worldwide sales of Zyprexa fell 5% to $1.04 billion. Sales in the United States fell 17% to $517.4 million because competing drugs are reducing demand for Zyprexa, the company said. U.S. sales of the treatment for schizophrenia and other disorders brought in $2.4 billion for Lilly last year. The drug had worldwide sales of $4.4 billion in 2004.

However, Lilly prevented further erosion of the still lucrative U.S. franchise for the drug when a federal judge in April upheld its patent giving its exclusive U.S. rights until 2011. The case could still face appeals.

Lilly to settle for up to $690M
indystar.com 10.6.2005
Deal may resolve 8,000 Zyprexa claims
Eli Lilly and Co. said Thursday it will pay up to $690 million to settle legal claims by about 8,000 patients alleging they were harmed by the antipsychotic Zyprexa, Lilly's top-selling drug.

The proposed settlement comes six months before the first trial in a rash of Zyprexa lawsuits is scheduled to begin in federal court in New York.

The Indianapolis drug maker said it's not admitting in the agreement that its star drug caused the diabetes-related injuries alleged by claimants, many of whom are schizophrenia patients. The drug also is approved to treat manic depression.

"While we believe the claims are without merit, we took this difficult step because we believe it is in the best interest of the company, the patients who depend on this medication, and their doctors," said Lilly President Sidney Taurel in a statement.

The agreement in principle covers about 75 percent of the filed or pending claims that Lilly knows about in the Zyprexa litigation, the company said. The final wording of the deal has to be approved by both sides.

"This takes the lion's share of the risk to the company off the table," said a Lilly executive vice president, John Lechleiter.

He said the settlement would remove a major distraction to Lilly and allow it to devote more time and resources to marketing Zyprexa.

A New York plaintiff's attorney, Jerrold Parker, said: "It's really remarkable to arrive at a settlement of this magnitude so early" in the litigation process. The proposed settlement comes before federal Judge Jack Weinstein has ruled on whether the hundreds of lawsuits being consolidated in his court in New York can be combined as a class action.

Parker said a team of trial attorneys from 12 firms, including some of the best-known product litigators in the nation, "were able to demonstrate to Lilly extremely early in the litigation there were certain possibilities they had to face up to. They (Lilly) realized their exposure and decided to live up to the consequences."

Parker estimated about $500 million of the settlement money will go to patients, after subtracting nearly $200 million for attorney fees and costs of claims administration.

Patients would be compensated in large part on the extent of their alleged injuries, although guidelines have not been drawn up, Parker said.

"There's a range of injuries here, from a little weight gain to death," he said.

If $500 million were split equally among the 8,000 patients, the average payout would come to $62,500. Claimants would be allowed to opt out of the agreement and individually pursue their claims. (...)

Lilly said it would take a $700 million charge against earnings in the current quarter to cover the cost of the settlement.

The company said it will continue to fight in court any new Zyprexa lawsuits that are filed.

Many of those who have sued Lilly allege the company failed to warn patients and doctors of Zyprexa's link to diabetes, possibly caused by a side effect of weight gain.

While Zyprexa was launched on the U.S. market in 1996, Lilly did not add a significant warning about the risk of diabetes and hyperglycemia to the drug's label until September 2003. That warning was required by the Food and Drug Administration for all antipsychotics in Zyprexa's class.

Lilly has maintained that its drug is not to blame for diabetes-related problems. Lechleiter said schizophrenia patients are prone to weight gain and also suffer a fourfold greater incidence of diabetes than the general population.

The agreement also would result in the dismissal of claims against physicians and other health care professionals named as co-defendants, Lilly said.

Zyprexa, which is taken in pill form, became Lilly's best-selling drug after Prozac lost U.S. patent protection in 2001. Last year Zyprexa generated almost a third, or $4.4 billion, of Lilly's total sales of $13.86 billion.

In part because of the litigation and charges that the drug caused diabetes, Zyprexa's U.S. sales have been slowing.

Lilly's settlement was announced after the markets closed. Lilly shares closed Thursday at $57.07, down 30 cents.

Zyprexa Trial in Schizophrenia 'Prodome' Yields Only Hints
medpagetoday.com 3.5.2006
(...) NEW HAVEN, Conn., May 3 — A two-year study of Zyprexa (olanzapine) in patients thought to have early signs of schizophrenia had mixed results, researchers reported.

On one hand, daily Zyprexa appeared to blunt symptoms and delay the onset of full-blown schizophrenia, according to Thomas McGlashan, M.D., of Yale and colleagues in the multicenter Prevention Through Risk Identification, Management, and Education (PRIME) project.

On the other hand, patients taking Zyprexa had large weight gains and the dropout rate in the study was so high that no definitive conclusions about the efficacy of the drug could be drawn, the researchers reported in the May issue of the American Journal of Psychiatry. (...)

(Anm: Randomized, Double-Blind Trial of Olanzapine Versus Placebo in Patients Prodromally Symptomatic for Psychosis. Am J Psych 2006; 163:790-799.)

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