MinTankesmie

- Mange får antidepressiva uten psykiatrisk grunn

Læger kan skubbe medicinmisbrugere ud i alkoholisme
information.dk 1.8.2011
En intensiv indsats har kraftigt reduceret danskernes årelange overforbrug af sove- og angstmedicin. Men der er ingen afvænningstilbud til den procentdel, der er blevet afhængige, og det er et problem, påpeger Sundhedsstyrelsen. Misbruget kan blive erstattet med alkohol.

Det danske sundhedsvæsen risikerer at skubbe folk fra det ene misbrug ud i et andet, når man forsøger at reducere danskernes overforbrug af medicin.

Ifølge tilsynschef i Sundhedsstyrelsen Anne Mette Dons er det problematisk, at der ikke eksisterer nogen tilbud for de medicinafhængige på eksempelvis sove- og nervemedicin. (...)

Sove- og angstmedicinen benzodiazepin kaldes også tørsprit og virker samme sted i hjernen som alkohol. Derfor vil en del af de afhængige formentlig erstatte medicinen med alkohol, hvis ikke de bliver ordentligt afvænnet,« siger misbrugsekspert Henrik Rindom, der er psykiatrisk overlæge på Hvidovre Hospital. (...)

(Anm: Alkohol (mintankesmie.no).)

Antidepressant Scripts Often Lack Diagnosis (Forskrivninger av antidepressiva mangler ofte diagnoser)
medpagetoday.com 8.8.2011
Nesten trefjerdedeler av forskrivninger av antidepressiva skrevet av ikke-psykiatere hadde ingen dokumentasjon på psykiatriske diagnoser, ifølge en nylig analyse av forskrivningstrender. (Almost three-quarters of the antidepressant prescriptions written by nonpsychiatrists had no documentation of psychiatric diagnoses, an analysis of recent prescribing trends showed)

Prescriptions without psychiatric diagnoses accounted for a majority of nonpsychiatrists' antidepressant prescriptions from 1996 to 2007, according to an article published online in Health Affairs.

And the proportion of prescriptions without documented psychiatric indications increased from about 60% to almost 73% over the study period. (...)

(Anm: Patients Getting Antidepressants More Often From Nonpsychiatrists Without Psychiatric Diagnoses. Health Aff 2011 (August).)

(Anm: Proportion Of Antidepressants Prescribed Without A Psychiatric Diagnosis Is Growing. Health Aff 2011; 30(8):1434-1442 (August).)

Many get antidepressants for no psychiatric reason (Mange får antidepressiva uten psykiatrisk grunn)
reuters.com 4.2.2011
(Reuters Health) - More than a quarter of Americans taking antidepressants have never been diagnosed with any of the conditions the drugs are typically used to treat, according to new research.

Det betyr at millioner kan være eksponert for sideeffekter fra legemidlene uten bevis på helsenytte, ifølge forskerne (That means millions could be exposed to side effects from the medicines without proven health benefits, researchers say.)

"We cannot be sure that the risks and side effects of antidepressants are worth the benefit of taking them for people who do not meet criteria for major depression," said Jina Pagura, a psychologist and currently a medical student at the University of Manitoba in Canada, who worked on the study. (...)

(Anm: Antidepressant Use in the Absence of Common Mental Disorders in the General Population. J Clin Psychiatry 2011 (Online ahead of print: January 25).)

- Industrisponset skjevhet i kostnadseffektivitetsanalyser

Industry sponsored bias in cost effectiveness analyses (Industrisponset skjevhet i kostnadseffektivitetsanalyser)
Editorial (Lederartikkel)
BMJ 2010; 341:c5350 (13 October)
Det fremkommer stadig flere bevis på at industriens innblanding i kostnadseffektivitetsanalyser kan påvirke resultatene. En systematisk gjennomgang av publiserte kost-nytteverdi-analyser fant at industrifinansierte studier var mer enn dobbelt så sannsynlig å rapportere kost-nytteverdi-forhold under 20 000 dollar (£12 700; $14 850) per “kvalitetsjusterte leveår” (QALY) enn studier som ikke er finansiert av industrien.¹ National Institute for Health og Clinical Excellence (NICE) i Storbritannia fant at kostnadseffektivitetsanalyser fremlagt av produsenter kom frem til signifikant lavere forholdstall enn de som stammet fra akademiske sentre.² (...) (Evidence is growing that the involvement of industry in cost effectiveness analyses can affect the findings. A systematic review of published cost-utility analyses found that industry funded studies were more than twice as likely to report a cost-utility ratio below $20 000 (£12 700; $14 850) per quality adjusted life year (QALY) as studies sponsored by non-industry sources.¹ The National Institute for Health and Clinical Excellence (NICE) in the United Kingdom found that cost effectiveness analyses submitted by manufacturers produced significantly lower ratios than those derived by assessors at academic centres.²)

(Anm: Interessekonflikter, bestikkelser og korrupsjon (mintankesmie.no).)

- Forringede medisinske bevis

Evidence debased medicine (Forringede medisinske bevis)
BMJ 2010; 341:c5715 (13 October)
Dagens bevisgrunnlag for nytteverdi og skadelige virkninger for mange behandlinger inneholder mangelfulle og tvilsomme bevis. Denne uken krever Elizabeth Loder og Fiona Godlee at man får saker og ting på plass og presenterer en temautgave av BMJ sent i 2011 for forskning som analyserer ikke fremlagte bevis (doi:10.1136/bmj.c5641). Målet er å gjenopprette tilliten til bevisgrunnlaget, ikke for å rette pekefingre. (doi:10.1136/bmj.c5641). (Our current evidence base on the benefits and harms of many treatments contains incomplete and questionable evidence. This week Elizabeth Loder and Fiona Godlee call for the record to be set straight and announce a BMJ theme issue in late 2011 for research that analyses uncovered evidence (doi:10.1136/bmj.c5641). The aim is to restore trust in the evidence base, not to point fingers.)

This is an early call, but such studies take time because they often depend on freedom of information requests and protracted negotiations with companies. Dirk Eyding, Beate Wieseler, and colleagues from the German Institute for Quality and Efficiency in Health Care (IQWiG) show how it’s done.
Their health technology assessment of the antidepressant reboxetine began in the usual way last year with an extensive literature search for primary and secondary studies (doi:10.1136/bmj.c4737). They found a yawning gap: around 4600 people had taken part in trials of reboxetine, yet adequate data on outcomes had been published for only 1600 or so of the participants (doi:10.1136/bmj.c4942). Over the next seven months the institute issued its preliminary conclusion that no benefit of reboxetine could therefore be proved; Pfizer (the drug’s manufacturer) stated “we provided IQWiG with sufficient data” but then released most of the missing data; and the full assessment showed that, overall, reboxetine had no benefit. At the start, IQWiG had asked the manufacturer to sign an agreement requiring: (1) submission of a list of all sponsored published and unpublished trials investigating reboxetine; (2) submission of documents (generally the clinical study reports) compliant with the CONSORT criteria for all relevant trials selected by IQWiG; and (3) permission for publication of all previously unpublished relevant data. (...)

(Anm: reboxetine (Edronax) (felleskatalogen.no).)

Firmaer skjuler negative medicinforsøg
ekstrabladet.dk 13.10.2010
Medicinalfirmaerne vildleder forbrugerne ved kun at offentliggøre de testresultater, som kommer positivt ud, advarer forskere (...)

Læger og patienter bliver ført bag lyset af medicinalfirmaerne, som skjuler negative resultater fra kliniske forsøg, så deres medicin fremstår mere effektiv end den er, advarer eksperter. (...)

Et tysk forskerhold har i det anerkendte tidsskrift British Medical Journal offentliggjort en gennemgang af ikke tidligere offentliggjorte forsøg med antidepressivet reboxetine (Edronax). De konkluderer, at medicinen ikke er blevet fremstillet i et sandfærdigt lys, skriver BBC.co.uk. (...)

'Vores fund understreger det tvingende behov for tvungen offelitggørelse af førsøgsdata' konkluderer undersøgelsens bagmænd ifølge BBC.co.uk. (...)

Undersøgelsen kommer i kølvandet på flere kritiske historier om medicinalindustrien: Medicinalgiganten Glaxo Smith Kline er ligesom Pfizer blevet anklaget for at tilbageholde kritiske resultater i forhold til diabetesmedicinen Avandia og antidepressivet Seroxat.

Tidligere på måneden blev medicinalfirmaerne i bogen 'Sex, lies and Pharmaceuticals' anklaget for at opfinde nye sygdomme og sygeliggøre raske, så de kunne sælge mere medicin. (...)

Finding studies on reboxetine a tale of hide and seek (Funn i studier på reboxetine en historie om hemmelighold)
BMJ 2010; 341:c4942 (12 October)
Beate Wieseler, Natalie McGauran, and Thomas Kaiser use their experience with the assessment of reboxetine to illustrate how publication bias affects health policy decisions and offer some solutions

The antidepressant reboxetine, a selective noradrenaline (norepinephrine) reuptake inhibitor, has been approved in several European countries (including the United Kingdom and Germany) since 1997. However, approval was declined in the United States in 2001. The German Institute for Quality and Efficiency in Health Care (IQWiG) report on the benefit and harm of newer antidepressants concluded in 2009 that, overall, reboxetine was both ineffective and potentially harmful.^{1 2} (...)

(Anm: reboxetine (Edronax) (felleskatalogen.no).)

Data availability for industry sponsored trials: what should medical journals require? (Datatilgjengelighet for industrisponsede forsøk: hva bør medisinske tidsskrifter kreve?)
BMJ 2010; 341:c5391 (12 October)
Several recent examples illustrate the problems of trusting drug companies to provide the complete picture about the clinical trials they sponsor. Robert Steinbrook and Jerome P Kassirer propose that there is a strong case for journals defining full access to the trial data and requiring that investigators and journal editors have full access. (...)

Companies have financial interests in the outcome of the studies they sponsor; they own the data, and set the rules for access to the data. Unfortunately, they cannot be relied on to consistently provide dispassionate evaluations of their own drugs and medical devices.¹¹ Moreover, many investigators have notable financial interests with the same sponsors. According to the voluntary principles of the Pharmaceutical Research and Manufacturers of America, “As sponsors, we are responsible for receipt and verification of data from all research sites for the studies we conduct; we ensure the accuracy and integrity of the entire study database, which is owned by the sponsor.”¹² These obligations may be appropriate, but it has become impossible to assess which industry studies are trustworthy. (...)

Drug firms 'must publish all data' (Legemiddelfirmaer "må publisere alle data")
google.com/hostednews/ukpress/article 13.10.2010 (The Press Association)
Drug companies should be forced to publish all their trial data rather than selecting evidence to back up their claims, experts have said. (...)

Publication bias refers to positive trial results being more likely to be published than those that are unfavourable. (...)

The authors wrote: "Published data overestimated the benefit of reboxetine versus placebo by up to 115% and reboxetine versus SSRIs by up to 23%, and also underestimated harm. Reboxetine is, overall, an ineffective and potentially harmful anti-depressant.

"Published evidence is affected by publication bias, underlining the urgent need for mandatory publication of trial data." (...)

(Anm: reboxetine (Edronax) (felleskatalogen.no).)

Drug trial claims 'misleading' (Påstander i legemiddelforsøk villedende)
hc2d.co.uk 13.10.2010
Experts writing in the British Medical Journal have suggested that doctors and patients are being misled about the effectiveness of some drugs because negative trial results are not published. (...)

Writing in the BMJ, they say the findings "underline the urgent need for mandatory publication of trial data".

The MHRA said: "There is a European initiative to provide public access to the results of clinical trials. The currently planned timeline is that this information could become available in 2011/12."
Pfizer said reboxetine is licensed in the UK for the acute treatment of depressive illness and that it presents an effective treatment option.

A spokesman added that Pfizer discloses the results of its clinical trials "to regulatory authorities all around the world" who "carefully balance the risks and benefits of each medication". (...)

(Anm: reboxetine (Edronax) (felleskatalogen.no).)

Patients and Doctors Are Being Misled by Published Data on Medicines, Germany Study Suggests (Tysk studie tyder på at pasienter og leger er blitt villedet av publiserte data for legemidler)
sciencedaily.com 16.10.2010
ScienceDaily (Oct. 12, 2010) — The drug reboxetine is, overall, an ineffective and potentially harmful antidepressant, according to a comprehensive study of the evidence published online in the British Medical Journal.

The study also shows that nearly three quarters of the data on patients who took part in trials of reboxetine were not published until now, and that the published data on the drug overestimate the benefits and underestimate the harms of treatment -- all underlining the urgent need for mandatory publication of all clinical trial results. (...)

They show that reboxetine is, overall, an ineffective and potentially harmful antidepressant. They found no significant difference in benefit (remission and response rates) versus placebo and inferior benefit versus SSRIs, as well as a higher rate of patients affected by adverse events than with placebo and higher withdrawal rates owing to adverse events than with placebo and the SSRI fluoxetine.

A further comparison of published and unpublished trials shows that published data overestimated the benefit of reboxetine and underestimated harm. (...)

(Anm: reboxetine (Edronax) (felleskatalogen.no).)

Journals mislead public over drugs (Tidsskrifter villedet publikum om legemidler)
presstv.ir 16.10.2010
While drugs should undergo various tests before receiving approval in Europe, pharmaceuticals often mislead consumers and authorities by not publishing the results.

According to an article published in the British Medical Journal, pharmaceuticals only publish the positive points of the trial. The publication bias overestimates the benefits of many medications. (...)

Experts criticise new German law for favouring drug companies (Eksperter kritiserer ny tysk lov for å favorisere legemiddelfirmaer)
BMJ 2010; 341:c5650 (13 October)
En ny lov som godkjenner legemidler for godtgjørelse av tyske forsikringsfirmaer er for tiden debattert i parlamentet kan utsette pasienter for risiko, advarer eksperter (A new law on approving drugs for reimbursement by German insurance companies currently being debated in parliament could put the safety of patients at risk, experts have warned.)

The law would substantially weaken the role of the German Institute for Quality and Efficiency in Health Care (IQWiG), the German equivalent of the UK National Institute for Health and Clinical Excellence, and lead to inefficient and dangerous drugs being approved, say experts.

An amendment to the law proposed by the governing coalition of the Christian Democrats and the liberal Free Democratic Party says that all new drugs admitted to the market should be reimbursed by health insurance companies unless they are proved to be inefficient.

Under current regulations new drugs are excluded from reimbursement if they have severe side effects or if no additional advantages over drugs already on the market have been proved. These requirements would disappear under the new law.

Parlamentsmedlemmer som var imot og som kritisertre regjeringen hevder at det er banet vei for lobbying fra legemiddelindustrien. (Opposition MPs have criticised the government, claiming that it has given way to lobbying from the drug industry.)

Drugs are presently admitted on the German market if they fulfil certain standards of efficiency and safety. However, IQWiG focuses solely on pharmacological criteria, such as reduction of hypertension or blood glucose concentrations. It is down to the Federal Joint Committee of the German healthcare system to decide whether a drug improves outcomes and quality of life, has no major side effects, and should be refunded by the health insurance companies. The committee asks IQWiG to analyse and prepare the scientific evidence for its decision.

Under the new law the committee will have to base its decision to reject reimbursement of a drug’s cost on proved inefficiency.

But Jürgen Windeler, the director of IQWiG, said, “We cannot prove that inefficiency is there. There are no studies, least of all by the pharmaceutical industry.”

Reiner Hess, the head of the joint committee, told Der Spiegel magazine on 4 October, “This reversal of the burden of proof jeopardises patient safety.” He criticised the fact that in future the health ministry, not the joint committee, will set the criteria for reimbursement of drug costs. He also condemned the new regulation, which would automatically certify all drugs for rare diseases as they came on the market. (...)

(Anm: Lobbyisme (lobbying – lobbyregister - interessekonflikter - korrupsjon) (mintankesmie.no).)

- Bivirkninger om lykkepiller ble skjult

Bivirkninger om lykkepiller blev skjult
b.dk 27.10.2011
Medicinalfirmaer politianmeldes for at tie om døde babyer

Medicinalfirmaer har skjult, at kvinder risikerer aborter, dødfødte babyer og misdannede børn, hvis de spiser lykkepiller under graviditeten. (...)

Producenterne blev i juni pålagt at advare om bivirkningerne efter, at det var kommet frem, at myndighederne havde fået 51 indberetninger om alvorlige bivirkninger ved lykkepiller fra danske gravide. Herunder 12 indberetninger om aborter og fosterdød og fire om døde babyer. (...)

Det er jo ganske alvorlige bivirkninger, som de skulle fortælle om - bl.a. at gravide risikerede misdannede babyer og at abortere?

- Ja, når vi advarer er det jo alvorligt. Derfor har vi krævet, at de trækker de pakninger tilbage, hvor advarslen ikke står på indlægssedlen, siger afdelingschef Anne-Marie Vangsted til B.T.

Foreningen for den danske medicinalbranche LIF er særdeles fåmælte om sagen.

- Ingen kommentarer, skriver kommunikationschef Lars Bech Pedersen i en sms. (...)

- Gjør antidepressiva mer skade enn nytte?

Are antidepressants doing more harm than good? (Gjør antidepressiva mer skade enn nytte?)
canada.com 26.10.2011
Doctors, scientists and Big Pharma industry have not been honest in what they tell the public about psychiatric drugs, says Robert Whitaker, author of Anatomy of an Epidemic, Magic Bullets, Psychiatric Drugs and the Astonishing Rise of Mental Illness. (...)

All is not well in the land of antidepressants.

Doctors, scientists and Big Pharma industry have not been honest in what they tell the public about psychiatric drugs, says Robert Whitaker, author of Anatomy of an Epidemic, Magic Bullets, Psychiatric Drugs and the Astonishing Rise of Mental Illness.

Whitaker's book eloquently argues that psychiatric drugs — including brand-names such as Prozac, Zoloft and Paxil and antipsychotics such as Risperdal, Zyprexa, and Seroquel — are driving an epidemic of drug-induced mental illness.

Perhaps better detection and various cultural factors contribute to the spike in the number of disabled mentally ill in society, Whitaker told the Montreal Gazette. (...)

Author questions use of antidepressant drugs (Forfatter stiller spørsmål ved bruk av antidepressiva)
montrealgazette.com 26.11.2011
Psychiatric drugs are driving an epidemic of drug-induced mental illness: Whitaker

Author Robert Whitaker argues that Prozac, Zoloft and other psychiatric medications are driving an epidemic of drug-induced mental illness.

Doctors, scientists and Big Pharma have not been honest in what they tell the public about psychiatric drugs, says Robert Whitaker, author of Anatomy of an Epidemic, Magic Bullets, Psychiatric Drugs and the Astonishing Rise of Mental Illness.

Whitaker's book argues that psychiatric drugs - including brand names such as Prozac, Zoloft and Paxil and antipsychotics such as Risperdal, Zyprexa and Seroquel - are driving an epidemic of drug-induced mental illness.

Perhaps better detection and various cultural factors contribute to the spike in the number of disabled mentally ill in society, Whitaker told The Gazette.

But studies looking at health outcomes suggest a different story, Whitaker said: The very drugs prescribed to treat mental disorders are inducing changes in brain chemistry and triggering suicide, manic and psychotic episodes, among other illnesses.

Whitaker is in Montreal on Wednesday for a lecture titled Doing More Harm than Good? Time to revisit the use of psychiatric drugs.

One in five will experience mental illness. According to a 2006 Canadian government report, mental health is the No. 1 cause of disability in Canada, accounting for nearly 30 per cent of disability claims and 70 per cent of the total costs.

Drugs are now the mainstay of treatment, replacing "talk therapy" of the 1980s. Shouldn't the prevalence of mental illness be declining? (...)

"The bottom line is some people clearly do well - but you really do see a lot of harm with long-term use," Whitaker said. "Who do the drugs benefit and for how long? That's a more subtle question."

That's precisely the kind of debate that interests AMI-Québec, a grassroots organization committed to helping families manage the effects of mental illness, and which sponsored the event.

"We don't want people to stop taking their medication the next day but the issue is something we have to talk about," said AMI-Québec executive director Ella Amir. (...)

- Kognitiv terapi er (i motsetning til SSRI-er (lykkepiller)) effektivt mot PTSD

Cognitive Therapy Effective in Preventing PTSD (Kognitiv terapi effektivt mot PTSD)
medscape.com 6.12.2011
October 11, 2011 — Prolonged exposure (PE) therapy and cognitive therapy (CT) may help prevent chronic posttraumatic stress disorder (PTSD). However, drug therapy with the selective serotonin reuptake inhibitor (SSRI) escitalopram appears to have no efficacy, a new study shows.

In addition, the randomized controlled trial, which compared early- and delayed-exposure-based cognitive and pharmacological interventions to prevent PTSD, showed that delaying treatment did not increase the risk for chronic PTSD.

"The results of our study show that there are significant and similar preventive effects of PE and CT. Delaying PE did not affect the 9-month outcome," the investigators, led by Arieh Y. Shalev, MD, and colleagues from Hadassah University Hospital, Jerusalem, write.

"Imidlertid, "tilla de at "gruppen som gikk på escitalopram (Lexapro/Cipralex) klarte seg dårligere enn alle undergruppene etter 9 måneder ("[H]owever," they add, "the escitalopram subgroup fared worse than all the other groups at 9 months.")

According to the authors, the study, which was published online October 3 in the Archives of General Psychiatry, is "the first comparative study of early and delayed cognitive behavioral interventions for PTSD."

They also note that this is the first randomized controlled trial to test an SSRI for the prevention of PTSD. (...)

- Eksport av sykdom, gjør stor suksess

Exporting disease, making a killing (Eksport av sykdom, gjør stor suksess)
business-standard.com 19.5.2010
Dette er uten tvil en av de mest skremmende bøker jeg har lest den senere tid. Journalisten og forfatteren Ethan Watters fra San Francisco, som undersøker sosiale trender for publikasjoner som Wired og The New York Times Magazine, har skrevet en uhyggelig bok om hvordan multinasjonale farmasøytiske firmaer eksporterer ideer om at mentale sykdommer vanlig i USA for å oppnå stor gevinst på å markedsføre legemidler for slike tilstander i land som ikke har et konsept for slike ting som depresjon. (This is without question one of the scariest books I’ve read in recent times. Ethan Watters, a San Francisco-based journalist and author who explores social trends for publications such as Wired and The New York Times Magazine, has written a chilling book on how multinational pharmaceutical companies export ideas about mental illnesses common in the US to make a killing from marketing the drugs for such conditions in countries which had no concept of such things as depression.)

Mental illnesses popular in the US, such as post-traumatic stress disorder (PTSD), anorexia and depression, in particular, are now spreading across the world with the speed of contagious diseases, says Watters, who went about investigating why this was happening although different cultures view mental illnesses through a complex prism of religious, scientific and social attitudes. In short, the West, primarily the US, has been homogenising the way the world goes mad. (...)

(...) Sjakkstrekket var en reklamekampanje som beskrev depresjon som kokoro no kaze, “en sjelelig kulde”, en vanlig lidelse i hjernen som kunne ta livet av pasienter dersom de ikke ble medisinert. Innen et år etter at Seroxat (Paxil) kom på markedet i Japan oppnådde GSKs antidepressive legemiddel et salg på over 100 millioner dollar. I 2008 hadde salget økt til over én milliard dollar. Den tragiske ironien er at de nyere storskalaforsøk på SSRIer i Japan ikke har lykkes å vise noen form for positiv effekt. (The master stroke was an advertising campaign that described depression as kokoro no kaze, “a cold of the soul”, a common illness of the brain that could kill patients if they were not medicated. Within a year of Paxil, GSK’s top anti-depressant medication, coming into Japan, sales had topped $100 million. In 2008, it had crossed $1 billion. The tragic irony is that recent large-scale trials of SSRIs in Japan have failed to show any positive effects.)

Even if you’ve read The Truth About the Drug Companies, The $800-Million Pill or Selling Sickness, Watters’ book comes as an eye-opener. Among the more disturbing disclosures is his detailing of GSK’s dishonesty on Paxil. In-house assessments of the drug that have come to light through lawsuits and government inquiry reports show the drug has not been effective. He quotes a company memo that reported that results of Paxil were “insufficiently robust” and urged GSK to “effectively manage the dissemination of these data in order to minimise any potential commercial impact”.

Crazy like Us reveals what is undeniably the most disturbing aspect of globalisation so far. (...)

(Anm: Salg av sykdom (mintankesmie.no).)

(Anm: paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

(Anm: Ethan Watters. CRAZY LIKE US. The Globalisation of the American Psyche (amazon.com (17.6.2010).)

(Anm: Merrill Goozner. The $800 Million Pill: The Truth behind the Cost of New Drugs (amazon.com (17.6.2010)).)

- Antidepressiva: Negative resultater blir ikke publiceret

Antidepressivt läkemedel utan effekt
lakemedelsvarlden.se 14.10.2010
Nu kommer ännu ett larm om att opublicerade data har påverkat bilden av effektiviteten hos ett läkemedel. Forskare som har granskat reboxetin menar att preparatet är verkningslöst mot depression och dessutom kan ge allvarliga bieffekter.

SNEDVRIDET I genomgången analyserade forskarna 13 studier med reboxetin. Åtta av dessa hade aldrig publicerats och omfattar 74 procent av alla patienter som har ingått i kliniska prövningar med reboxetin. Resultaten visar att reboxetin inte har någon effekt jämfört med placebo. De patienter som tog preparatet fick däremot fler allvarliga biverkningar och avslutade oftare behandlingen.

Publicerade studier överdrev effekten av substansen och underdrev biveffekterna, konstaterar forskarna som nu rapporterar sina resultat i British Medical Journal.

Reboxetin säljs under namnet Edronax och är sedan 1997 godkänt för användning i Sverige. Förra året såldes Edronax för lite över sju miljoner kronor. Forskarnas misstankar om preparatets ineffektivitet väcktes när det fick avslag i USA 2001. (...)

(Anm: Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials. BMJ 2010; 341:c4737 (12 October).)

(Anm: reboxetine (Edronax) (felleskatalogen.no).)

Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials.
BMJ 2010; 341:c4737 (12 October)
Objectives To assess the benefits and harms of reboxetine versus placebo or selective serotonin reuptake inhibitors (SSRIs) in the acute treatment of depression, and to measure the impact of potential publication bias in trials of reboxetine.

Design Systematic review and meta-analysis including unpublished data. (...)

Conclusions Reboxetine is, overall, an ineffective and potentially harmful antidepressant. Published evidence is affected by publication bias, underlining the urgent need for mandatory publication of trial data. (...)

Table 4 Examples of publication bias and industry sponsorship bias in trials of antidepressants

In addition to publication bias, outcome reporting bias has been identified as a major problem in the reporting of clinical trials, resulting in a distorted public record of an intervention.^{35 36 37 38} Our review also identified this type of bias—for three reboxetine trials, only results on subpopulations or selected outcomes were available in the published literature (trials 047, 050, 052; table 1).

The more positive benefit-risk ratio in published data compared with unpublished data also affects the content of clinical guidelines. For example, the National Institute for Health and Clinical Excellence (NICE) guideline on the treatment and management of depression in adults is based on published studies of reboxetine, and concludes that “Reboxetine is superior to placebo and as effective as other antidepressants in the treatment of depression.”¹⁰ In our opinion, this conclusion can no longer be upheld.

The ongoing problem of publication bias shows that unbiased decision making in health care requires mandatory public disclosure of all clinical trial data. The US FDA Amendments Act of 2007³⁹ solves the problem in part by requiring protocol information and study results for clinical trials to be made public on the clinicaltrials.gov website (www.clinicaltrials.gov; please see accompanying comment (doi:10.1136/bmj.c4942) for further details). Similar legislation is also being introduced in Europe, with the mandatory public disclosure of data from the clinical trials database EudraCT (eudract.ema.europa.eu),^{40 41} but the date of implementation is not yet clear.

As the full assessment reports on reboxetine prepared by regulatory authorities are not publicly available, it is not clear as to how the comprehensive body of evidence (including that on efficacy outcomes) generated after reboxetine was approved in Europe in the late 1990s has been analysed by these authorities. The reason for the difference in approval status of reboxetine between Europe and the US thus remains unclear.(...)

Tvivl om antidepressiv medicin
videnskab.dk 21.9.2009
En kritisk artikel i det højt ansete, videnskabelige tidsskrift The New England Journal of Medicine har sat spørgsmålstegn ved effekten af 'lykkepiller'. (...)

Kun positive resultater publiceret
Faktisk var der nøjagtig lige mange undersøgelser med positive resultater (36), som med direkte negative resultater (24) samt tvivlsomme resultater (12), der hverken var klart positive eller negative med hensyn til en tydelig virkning af den antidepressive medicin. (...)

Resultater 'fordrejet'
Det amerikanske forskerhold bag den omtalte kritiske gennemgang af forskningen vedrørende effekten af antidepressiv medicin mener altså, at resultaterne bliver "fordrejet" i en retning til fordel for medicinalindustrien, der producerer denne medicin, dels ved at negative resultater holdes skjult, og dels ved at negative eller tvivlsomme resultater fremstilles som om de var positive, selvom det - ifølge forskerholdets egne analyser - ikke var tilfældet. (...)

- Lykkepillen fungerer ikke
vg.no 26.2.2008
(...) INGEN EFFEKT: En ny undersøkelse setter spørsmålstegn ved virkningene av Prozac og andre antidepressiver. (...)

En omfattende britisk undersøkelse av antidepressiver konkluderer med at de ikke har noen betydelig klinisk effekt. (...)

- Ikke slutt
I studien, som ble ledet av prosessor Irving Kirsch, ble 47 tidligere kliniske forsøk analysert. Dette var både publiserte og upubliserte forsøk, som var registrert hos FDA (The Food and Drug Administration).

Psykiater Jørgen Bramness ved Folkehelseinstituttet, synes det er positivt at det gjøres undersøkelser på dette feltet. Samtidig understreker han at folk som går på disse medisinene ikke må kutte dem ut. (...)

Professoren som ledet arbeidet med studien, Irving Kirsch, mener disse nye oppdagelsene gjør at man må sette spørsmålstegn ved lisensieringen av slike medisiner. (...)

Antidepressiva: Negative resultater bliver ikke publiceret
irf.dk 13.2.2008 (Institut for Rationel Farmakoterapi (IRF)
Nyt amerikansk studie viser, at den videnskabelige litteratur om moderne antidepressiva er misvisende pga. selektiv publicering af positive fund, så lægemidlernes effekt overvurderes.

Kort om studiet
• Formålet med studiet var at undersøge i hvilken grad den information om et lægemiddel, som man få ved en systematisk litteratursøgning, er i overensstemmelse med den information om lægemidlet, som findes i en lægemiddelmyndigheds database.

• Forfatterne udgik fra 74 kliniske forsøg, der omhandlede den antidepressive effekt af de 12 antidepressiva, som den amerikanske lægemiddelmyndighed FDA havde godkendt til markedsføring i perioden 1987-2004, fx citalopram, escitalopram, sertralin, mirtazapin, venlafaxin og duloxetin. Studierne blev klassificeret som positive, tvivlsomme eller negative i henhold til FDA’s vurdering.
• 33 af 36 (92 %) negative eller tvivlsomme studier var enten ikke videnskabeligt publiceret eller publiceret med en positiv konklusion i strid med FDA’s vurdering.
• Kun 1 af 38 positive studier var ikke publiceret.
• Positive studier havde ca. 12 gange større sandsynlighed for at være publiceret på linie med FDA’s konklusion end ikke-positive studier (95 % CI 6,2-22,0; P<0,001).
• I 94 % af de videnskabelige artikler fremstod resultaterne som positive. Det skal sammenlignes med kun 51 % af studierne i FDA’s analyse.
• Effekten mod depression for de 12 antidepressiva blev vurderet 32 % højere, hvis man udgik fra den systematiske litteratursøgning, end hvis man udgik fra FDA’s database. (...)

Det mener IRF
Disse fund er rystende, men egentlig ikke overraskende. Lignende fund er tidligere set i studier fra USA, Europa og Danmark. (...)

Med tanke på, at de videnskabelige publikationer tilsyneladende giver et for optimistisk billede af antidepressivas effektivitet (1), og at effekten på depression, udover placeboeffekten, tilsyneladende er ret lille (2) og muligvis delvist kan forklares af ineffektiv blindning i studierne (5), må man spørge, om denne fortsatte stigning er rationel for patienter, samfund og den fortsatte udvikling af vigtig viden på området. (...)

- Negative legemiddelstudier publiseres ikke, ifølge rapport

Unfavorable drug studies don't see print: report (Negative legemiddelstudier publiseres ikke, ifølge rapport)
reuters.com 17.1.2008
BOSTON (Reuters) - Nearly a third of antidepressant drug studies are never published in the medical literature and nearly all happen to show that the drug being tested did not work, researchers reported on Wednesday.

And in some of the studies that are published, unfavorable results have been recast to make the medicine appear more effective than it really is, said the research team led by Erick Turner of the Oregon Health & Science University. (...)

The idea that unfavorable test results get quietly tucked away so nobody will see them -- sometimes call the "file drawer effect" -- has been around for years. (...)

They could see which experiments approved by the FDA between 1987 and 2004 were ultimately publicized in the medical literature and the main criteria the researchers planned to measure success.

"It tells you where they placed their bets before they saw the data," Turner said in a telephone interview. (...)

REWRITTEN STUDIES
However, when it came to the 36 studies with negative or questionable results, as assessed by the FDA, only three were published and another 11 were turned around and written as if the drug had worked.

"Not only were positive results more likely to be published, but studies that were not positive, in our opinion, were often published in a way that conveyed a positive outcome," said the team.

For example, of the seven negative studies done on GlaxoSmithKline's Paxil, five were never published. The researchers found three studies for GSK's Wellbutrin SR, but the two negative ones never reached print. (...)

"There's an expectation that if you get a positive result, that's what you're supposed to do, and if you get a negative result you have failed," said Turner. "The first impulse is to say, 'I was wrong. Maybe I should move on to something more interesting'" so the results may never get written up. (...)

Antidepressants Less Effective Than Doctors Have Been Led to Believe: Study
therapeuticsdaily.com 17.1.2008
TORONTO - Antidepressants are far less effective than doctors have been led to believe, a new study has found.

That's because 88 per cent of clinical trials that showed the drugs didn't work either weren't published in medical journals or were presented as positive findings, says the study in the New England Journal of Medicine. (...)

Snedvriden publicering om antidepressiva
lakemedelsvarlden 17.1.2008
Studier som visar negativa resultat för antidepressiva läkemedel publiceras inte i den vetenskapliga litteraturen. Det visar en jämförelse som forskare gjort mellan de studier som amerikanska läkemedelsverket har tillgång till och de studier som är offentliggjorda i medicinska tidskrifter. (...)

Lyver om negative legemiddelstudier
helserevyen.no 23.1.2008
I en gjennomgang har den amerikanske legemiddelmyndigheten, FDA, funnet at legemiddelindustrien underslår negative tester på antidepressive midler.

Undersøkelsen tyder på at effekten av antidepressive legemidler er sterkt overdrevet i forhold til testresultatene.

Grunnen er at negative resultat aldri blir offentliggjort, eller at de blir presentert som positive istedenfor negative, ifølge The Wall Street Journal. (...)

Antidepressants Less Effective Than Doctors Have Been Led to Believe: Study
therapeuticsdaily.com 17.1.2008
TORONTO - Antidepressants are far less effective than doctors have been led to believe, a new study has found.

That's because 88 per cent of clinical trials that showed the drugs didn't work either weren't published in medical journals or were presented as positive findings, says the study in the New England Journal of Medicine. (...)

Snedvriden publicering om antidepressiva
lakemedelsvarlden 17.1.2008
Studier som visar negativa resultat för antidepressiva läkemedel publiceras inte i den vetenskapliga litteraturen. Det visar en jämförelse som forskare gjort mellan de studier som amerikanska läkemedelsverket har tillgång till och de studier som är offentliggjorda i medicinska tidskrifter. (...)

Antidepressants Under Scrutiny Over Efficacy (Effekt av antidepressiva granskes)
wsj.com 17.1.2008
Sweeping Overview Suggests
Suppression of Negative Data
Has Distorted View of Drugs

The effectiveness of a dozen popular antidepressants has been exaggerated by selective publication of favorable results, according to a review of unpublished data submitted to the Food and Drug Administration.

ACCENTUATE THE POSITIVE

A review of research submitted to the FDA:
• Of 74 studies reviewed, 38 were judged to be positive by the FDA. All but one were published, researchers said.
• Most of the studies found to have negative or questionable results were not published, researchers found.
Source: The New England Journal of Medicine (...)

Five Trials
For example, Pfizer submitted five trials on its drug Zoloft to the FDA, the study says. The drug seemed to work better than the placebo in two of them. In three other trials, the placebo did just as well at reducing indications of depression. Only the two favorable trials were published, researchers found, and Pfizer discusses only the positive results in Zoloft's literature for doctors. (...)

The average effect size of the antidepressant Zoloft rose 64% by the failure to publish negative or questionable data on the drug, the researchers found. (...)

Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy (Selektiv publikasjon av forsøk på antidepressiva og dets innflytese på angivelig effektivitet)
NEJM 2008; 358:252-260 (January 17)
Background Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials — and the outcomes within those trials — can lead to unrealistic estimates of drug effectiveness and alter the apparent risk–benefit ratio. (...)

According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive. Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall.

Conclusions We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both. Selective reporting of clinical trial results may have adverse consequences for researchers, study participants, health care professionals, and patients. (...)

Antidepressant Studies Unpublished
nytimes.com 17.1.2008
Eli Lilly, manufacturer of Prozac, was among those criticized.

The makers of antidepressants like Prozac and Paxil never published the results of about a third of the drug trials that they conducted to win government approval, misleading doctors and consumers about the drugs’ true effectiveness, a new analysis has found. (...)

Antidepressant Trial Results Exaggerated (Forsøksresultater på antidepressiva overdrevet)
ivanhoe.com 16.1.2008
(Ivanhoe Newswire) – A new study shows a problem with past reporting of antidepressant research. The analysis finds selective publication in reporting exaggerates the effectiveness of antidepressants. (...)

Turner’s team found that whether and how the studies were published depended on how they turned out. They found 94 percent of the studies had positive results, but the FDA data showed only half of the study were positive. All but one of the positive studies was published. Most of the studies that were not positive were not published or they were published with a positive spin.

“Selective publication can lead doctors and patients to believe drugs are more effective than they really are, which can influence prescribing decisions,” says Turner. “Doctors and patients must have access to evidence that is complete and unbiased when they are weighing the risks and benefits of treatment.” (...)

Ingen større forskel på antidepressiva
irf.dk 17.9.2007
Institut for Rationel Farmakoterapi (IRF) har tidligere tilkendegivet, at der ikke er den store forskel på effekten blandt de nye antidepressiva, og at prisen derfor bør være en vigtig parameter i valget af behandling. En sundhedsøkonomisk analyse (1) sponsoreret af medicinalvirksomheden H. Lundbeck konkluderer imidlertid, at de totale udgifter ved brug af SSRI’et escitalopram (Cipralex) er lavere end generisk citalopram (Akarin, Cipramil, Citaham, Citalopram mfl.) og på niveau med venlafaxin (Efexor) over en seks måneders periode.

Det problematiske ved sundhedsøkonomiske analyser er generelt, at datagrundlaget er usikkert, ligesom der er mange faldgruber. Kvaliteten af analyserne afhænger blandt andet af validiteten af de kliniske studier. I dette tilfælde bygger analysen af escitalopram, citalopram og venlafaxin på udvalgte kliniske studier af 8-24 ugers varighed samt en spørgeskemaundersøgelse med ni praktiserende læger og 21 psykiatere. (...)

Antidepressive legemidler: Kun små forskjeller i effekt og bivirkninger avdekket
kunnskapssenteret.no 21.6.2007
(...) Det er bare avdekket små forskjeller i effekt og bivirkninger av nyere antidepressive legemidler. Studiene som sammenlikner legemidlene, er få og kortvarige, viser Kunnskapssenterets systematiske gjennomgang av litteraturen på området. (21.06.07) (...)

Kunnskapsgrunnlaget er av lav til middels kvalitet for de fleste sammenlikningene. (...)

Les rapporten ”Effekt og sikkerhet for SSRI og andre nyere antidepressive legemidler ved depresjon hos voksne” (pdf, 1MB) (...)

Eldre antidepressive legemidler ble brukt mindre enn dagens antidepressive legemidler bl.a. på grunn av bivirkningene. MAOI antidepressiver viste økt fare for hypertensive kriser særlig ved samtidig inntak av matvarer med høyt innhold av tyramin. TCA som ble mest brukt fra 1960- til 80-tallet hadde bivirkninger som søvnforstyrrelser, fare for omslag til hypomani, forvirringstilstander, tremor og i noen tilfeller ekstrapyramidale effekter (3). TCAs anti-histamin effekt ga sedasjon. Anticholinerge bivirkninger var bl.a. munntørrhet og forvirring, mens antiadrenerge bivirkninger ga blodtrykksproblemer med bl.a. svimmelhet. Den viktigste var imidlertid den toksiske påvirkningen av hjertets ledningssystem, som kunne gi hjerterytmeforstyrrelser og død ved overdoseringer. På bakgrunn
av dette ble det sett som et framskritt da nyere antidepressive medikamenter kom på markedet på slutten av 1980-tallet (mianserin og moklobemid) og rundt 1990 (SSRIpreparatene). (...)

Efficacy of antidepressants in adults (Effektivitet til antidepressiva hos voksne)
BMJ 2005;331:155-157 (16 July) (British Medical journal)
(...) Data fra NICE-gjennomgangen tyder på at selektive serotonin reopptakshemmere ikke har en klinisk relevant nytte over placebo, hvilket er i overensstemmelse med andre nylige metaanalyser. (...) (The NICE review data suggest that selective serotonin reuptake inhibitors do not have a clinically meaningful advantage over placebo, which is consistent with other recent meta-analyses.)

Depression study: Fewer steps better
dallasnews.com 1.12.2006
Odds of remission drop with repeated attempts at treatment, trial finds (...)

"If it takes more steps to get [better], you really have to be careful, because in the long run, you have more of a chance to relapse," said Dr. A. John Rush, the UT Southwestern psychiatrist who led the study. (...)

These findings, reported Wednesday in the American Journal of Psychiatry, are the latest from the six-year, $35 million STAR*D trial, the largest study to measure how well depression treatment works on everyday patients in private practice and public clinics, outside the structure of clinical trials. (...)

The researchers found that the remission rates were about 37 percent for the first level, 31 percent for the second level and 13 percent for both the third and fourth levels. Some patients dropped out of the study without reporting whether they went into remission, so it wasn't possible to calculate an overall remission rate with certainty.

Based on those numbers, the overall remission rate could be as high as 67 percent, but in actuality, it was probably lower, Dr. Rush said. (...)

(Anm: Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report. Am J Psychiatry 163:1905-1917 (November 2006).

Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report
Am J Psychiatry 163:1905-1917 (November 2006)
(...) RESULTS: The QIDS-SR16 remission rates were 36.8%, 30.6%, 13.7%, and 13.0% for the first, second, third, and fourth acute treatment steps, respectively. The overall cumulative remission rate was 67%. Overall, those who required more treatment steps had higher relapse rates during the naturalistic follow-up phase. In addition, lower relapse rates were found among participants who were in remission at follow-up entry than for those who were not after the first three treatment steps.

CONCLUSIONS: When more treatment steps are required, lower acute remission rates (especially in the third and fourth treatment steps) and higher relapse rates during the follow-up phase are to be expected. Studies to identify the best multistep treatment sequences for individual patients and the development of more broadly effective treatments are needed. (...)

In This Issue. Suicide and Antidepressants in Children
Am J Psychiatry 163:66A (November 2006)
(...) STAR*D: The Big Picture

In the Sequential Treatment Alternatives to Relieve Depression (STAR*D) study, remission was more common among patients in their first or second treatment trial (37% and 31%, respectively) than among those requiring three or four trials (14% and 13%). Rush et al. (p. 1905) also note that the 67% overall remission rate is misleading because many patients left the study after each step. Participants who required more treatment steps tended to have more chronic depression and more coexisting psychiatric and general medical disorders. Among responding patients who entered a follow-up period, relapse was associated with a lack of full remission and a higher number of treatment steps. Dr. Craig Nelson assesses what has been learned from STAR*D results in an editorial on p. 1864. (...)

Psykiater dømt til drøyt 8 års fengsel for svindel bl.a. i Seroxat-forsøk

Maria Carmen Palazzo: Debarment Order (Maria Carmen Palazzo: Kjennelse om utelukkelse)
federalregister.gov 28.3.2011
The Food and Drug Administration (FDA) is issuing an order under the Federal Food, Drug, and Cosmetic Act (the FD&C Act) permanently debarring Maria Carmen Palazzo, M.D. from providing services in any capacity to a person that has an approved or pending drug product application. We base this order on a finding that Dr. Palazzo was convicted of felonies under Federal law for conduct relating to the development or approval, including the process for development or approval, of any drug product or otherwise relating to the regulation of any drug product under the FD&C Act. Dr. Palazzo was given notice of the proposed permanent debarment and an opportunity to request a hearing within the timeframe prescribed by regulation. (...)

FDA's finding that debarment is appropriate is based on the felony convictions referenced herein for conduct relating to the development or approval, including the process for development or approval, of any drug product and otherwise relating to the regulation of any drug product under the FD&C Act. The factual basis for those convictions is as follows: Dr. Palazzo was a licensed medical doctor with offices located in New Orleans, Louisiana. SmithKline Beecham, Corporation, d.b.a. GlaxoSmithKline (SKB) was a pharmaceutical company engaged in developing, testing, and marketing pharmaceutical products including Paroxetine, also known as “Paxil.” Under the FD&C Act and its implementing regulations, SKB had to apply to FDA for approval to market Paxil. SKB was required to demonstrate, through clinical investigations in which Paxil was given to human subjects, the safety and effectiveness of the drug in order to receive approval from FDA. (...)

(Anm: paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

Paxil Researcher Pleads Guilty to Charges (Seroxat-forsker erklærer seg skyldig i anklager)
lawyersandsettlements.com 2.9.2010
Washington, DC: GlaxoSmithKline er gjenstand for mer dårlig publisitet etter at en forsker angivelig har forfalsket data i forsøk på Seroxat (Paxil). Samtidig er legemiddelfirmaet saksøkt grunnet påstander om at nyfødte er påført fødselsskader grunnet eksponering for Seroxat (Paxil) i svangerskapet. (Washington, DC: GlaxoSmithKline is the subject of more bad publicity after a researcher was allegedly found to have falsified data in trials about Paxil. Meanwhile, the drug maker faces lawsuits alleging newborns suffered Paxil Birth defects when they were exposed to Paxil prior to birth.)

The psychiatrist who reportedly falsified clinical data, Dr. Maria Carmen Palazzo, was a clinical investigator on studies conducted by SmithKline Beecham (doing business as GlaxoSmithKline). According to CNBC on 8/20/10, Palazzo has now pleaded guilty to 15 counts of failing to prepare and maintain records with the intent to defraud and mislead.

Palazzo reportedly included children in a study that involved diagnoses the children did not have. Prosecutors claimed that Palazzo also reported symptoms that her study subjects did not exhibit. She was sentenced to 13 months in prison, which she is serving at the same time as an 87-month term for healthcare fraud.

Ifølge BNET (08/19/10) ble Palazzo anklaget av den amerikanske legemiddelkontrollen FDA (Federal Drug Administration) for hennes innrullering av barn i studier med tvangslidelser (OCD) og tyngre depressive lidelser til tross for at barna hun undersøkte ikke hadde en egnet diagnose for inkludering i studien. (According to BNET (08/19/10), Palazzo was charged after the Federal Drug Administration (FDA) accused her of enrolling children in studies of obsessive-compulsive disorder and major depressive disorder even though the children she studied did not have the proper diagnosis for inclusion in the study.)

Paxil now carries a black box warning about the risk of suicide in children. It also carries a warning about the risk of birth defects in babies exposed to the antidepressant prior to birth. (...)

(Anm: paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

Jailed psychiatrist pleads guilty (Fengslet psykiater erkjenner seg straffeskyldig)
cnbc.com 20.8.2010
NEW ORLEANS – En 58 år gammel psykiater involvert i to kliniske forsøk som evaluerte legemidlet Seroxats (Paxils) sikkerhet og effekt hos barn og ungdommer har i forbindelse med disse kliniske forsøk erkjent seg straffeskyldig på 15 statlige tiltalepunkter for manglende utarbeidelse og oppfølging av protokoller, med den hensikt å bedra og villede. (NEW ORLEANS - A 58-year-old psychiatrist involved in two clinical trials evaluating the drug Paxil's safety and effectiveness in children and adolescents has pleaded guilty to 15 federal counts of failing to prepare and maintain records, with intent to defraud and mislead, in connection with those clinical trials.)

Dr. Maria Carmen Palazzo var klinisk forsker hos SmithKline Beecham som utførte arbeider under GlaxoSmithKline. Aktorene sa at hun i løpet av disse studier inkluderte psykiatriske diagnose uten overensstemmelse med pasienters psykiatriske historier; utarbeidet atskillige psykiatriske evalueringer på studiedeltakere som inneholdt forskjellige diagnoser og rapporterte symptomer hun visste studiedeltakerne ikke hadde. (Dr. Maria Carmen Palazzo was a clinical investigator for SmithKline Beecham doing business as GlaxoSmithKline. Prosecutors say that during those studies she included psychiatric diagnoses inconsistent with patients' psychiatric histories; prepared multiple psychiatric evaluations on study patients which contained different diagnoses and reported symptoms she knew the study subject did not demonstrate.)

Hennes tilståelse kom torsdag for den amerikanske distriktsdommeren Mary Ann Vial Lemmon, som dømte henne til 13 måneders fengsel. Denne tiden løper samtidig som hun soner en fengselsdom på 87-måneders for svindel innen helsevesenet. (...) (She entered the plea Thursday before U.S. District Judge Mary Ann Vial Lemmon, who sentenced her to 13 months in prison. That term will run at the same time as her current 87-month prison term for health care fraud.)

(Anm: paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

(Anm: Uredelighet og fusk i medisinsk forskning. (mintankesmie.no/).)

JAILED PSYCHIATRIST PLEADS GUILTY AND IS SENTENCED ON CHARGES OF FALSIFIED RECORDS OF CLINICAL TRIALS INVOLVING CHILDREN (FENGSLET PSYKIATER ERKLÆRER SEG SKYLDIG OG ER DØMT FOR ANKLAGER OM FORFALSKNING AV JOURNALER FOR KLINISKE FORSØK SOM INVOLVERER BARN)
justice.gov 19.8.2010
DR. MARIA CARMEN PALAZZO, age 58, pled guilty in federal court today before U. S. District Judge Mary Ann Vial Lemmon to fifteen (15) counts of failing to prepare and maintain records, with intent to defraud and mislead, in connection with clinical trials to evaluate the efficacy and safety of Paxil in children and adolescents with Obsessive-Compulsive Disorder (OCD), announced U. S. Attorney Jim Letten.

According to court documents, PALAZZO, who specialized in psychiatry, was a clinical investigator for SmithKline Beecham d/b/a GlaxoSmithKline, was involved in two clinical trials evaluating Paxil’s safety and effectiveness in children and adolescents. Some of the study records indicated that PALAZZO included psychiatric diagnoses inconsistent with patients’ psychiatric histories; prepared multiple psychiatric evaluations on study patients which contained different diagnoses and treatment plans; reported symptoms of OCD when PALAZZO knew that the study subject did not demonstrate such symptoms; and reported that PALAZZO examined study subjects when she had not.

PALAZZO is currently serving an 87 month prison sentence after being convicted of 39 counts of health care fraud following a 12-day trial in April 2008. In the instant case, PALAZZO was sentenced to thirteen (13) months in prison to run concurrent to the previous sentence as well as serve one (1) year of supervised release during which time she will be under federal supervision and risk additional imprisonment should she violate any rulesof the release. Additionally, PALAZZO was ordered to pay restitution to GlaxoSmithKline in the amount of $91,824 and $1,500 in special assessments.

The case was investigated by the Food and Drug Administration’s Office of Criminal Investigations, U. S. Department of Health and Human Services, Office of Inspector General, the Federal Bureau of Investigation and the Louisiana Medicaid Fraud Control Unit.

The case was prosecuted by Assistant U. S. Attorney Patrice Harris Sullivan, the Health Care Fraud Coordinator in this District.

(Download Factual Basis) (...)

(Anm: paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

10 Years Later, Glaxo Still Haunted by Faked Studies of Paxil in Kids (Glaxo 10 år senere fortsatt hjemsøkt av forfalskede studier på Seroxat hos barn)
bnet.com 19.8.2010
A crooked doctor who faked data in a GlaxoSmithKline (GSK) study of the antidepressant Paxil in children pled guilty to criminal charges today, causing groans among GSK’s senior management as the company hopes to fend off a different criminal investigation into whether it manipulated clinical data on its diabetes drug, Avandia. She was sentenced to 13 months in prison. (...) (A crooked doctor who faked data in a GlaxoSmithKline (GSK) study of the antidepressant Paxil in children pled guilty to criminal charges today, causing groans among GSK’s senior management as the company hopes to fend off a different criminal investigation into whether it manipulated clinical data on its diabetes drug, Avandia. She was sentenced to 13 months in prison.)

(Anm: paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

Psychiatrist indicted for fraud in Paxil trials (Psykiater anklaget for svindel i Seroxat-forsøk)
dailycomet.com 14.6.2007
NEW ORLEANS Dr. Maria Carmen Palazzo was indicted by a federal grand jury on 55 counts of health care fraud and false documentation in connection with a clinical trial of Paxil in children and adolescents, U.S. Attorney Jim Letten said on Thursday. (...)

According to the indictment, Palazzo, as a clinical investigator for SmithKline Beecham doing business as GlaxoSmithKline, fraudulently failed to maintain and prepare records required by the FDA for evaluation the drug's safety and effectiveness in children and adolescents.

If convicted, Palazzo faces a maximum term of 445 years, and a fine of $10.15 million, Letten's office said. (...)

(Anm: paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

- Hvorfor antidepressiva ikke alltid virker

Why Antidepressants Don't Always Work (Hvorfor antidepressiva ikke alltid virker)
depression.about.com 26.10.2009
Ifølge forskere ved Northwestern University har halvparten av de som får antidepressiva ingen nytte av midlene. Forskningen synes å indikere at det kan skyldes at hva vi tror trigger depresjon er fullstendig feil. (...) (According to background information provided in a new paper by Northwestern University researchers, over half of antidepressants fail to provide relief to depression sufferers. Their research seems to indicate it may be because what we believe about what triggers depression is entirely wrong.)

Konsekvensen av disse resultater? Redei og hennes gruppe konkluderte at stress ikke spiller noen rolle i trigging av genetiske endringer knyttet til depresjon; og, dersom stress ikke spiller noen rolle ved depresjon innebærer dette at antidepressiva, som stort sett er testet på dyr ved å stresse dyrene og så observere hvordan antidepressiva modifisere deres atferd, i virkeligheten behandler stress, ikke depresjon. (The implication of these results? Redei and her team concluded that stress does not play a role in triggering the genetic changes associated with depression; and, if stress does not play a role in depression then this means that antidepressants, which are generally tested on animals by stressing the animals and then observing how the antidepressant modifies their behavior, are actually treating stress, not depression.)

Redei sier at legemiddelutviklere har fokusert på effekten (stress) snarere enn årsaken til depresjon. "Det er derfor det tar så lang tid for midlene å virke og hvorfor de ikke er effektive for mange mennesker," forklarte Redei. De behandler faktisk ikke depresjon i det hele tatt. (...) (Redei says that drug developers have been focusing on the effect (stress) rather than the cause of depression. "That's why it takes so long for them to work and why they aren't effective for so many people," explained Redei. They are not actually treating depression at all.)

Northwestern Research Finds Antidepressant Drugs Aim At Wrong Target (Northwestern-forskning viser at antidepressiva bommer på målet)
medicalnewstoday.com 25.10.2009
More than half the people who take antidepressants for depression never get relief.

Why? Because the cause of depression has been oversimplified and drugs designed to treat it aim at the wrong target, according to new research from the Northwestern University Feinberg School of Medicine. The medications are like arrows shot at the outer rings of a bull's eye instead of the center. (...)

Both findings are significant because these beliefs were the basis for developing drugs currently used to treat depression.

Redei, the David Lawrence Stein Professor of Psychiatry at Northwestern's Feinberg School, found powerful molecular evidence that quashes the long-held dogma that stress is generally a major cause of depression. Her new research reveals that there is almost no overlap between stress-related genes and depression-related genes.

"Dette er en stor og statistisk sterk studie," uttalte Redei. "Denne forskningen åpner opp for nye veier for utvikling av antidepressiva som kan være mer effektive. Der har ikke vært et antidepressiva basert på et nytt konsept på 20 år." (...) ("This is a huge study and statistically powerful," Redei said. "This research opens up new routes to develop new antidepressants that may be more effective. There hasn't been an antidepressant based on a novel concept in 20 years.")

Why Antidepressants Don't Work For So Many
northwestern.edu 23.10.2009
CHICAGO --- For more than half the people who take antidepressants, relief from their symptoms never comes.

Why? Because the cause of depression has been oversimplified and drugs designed to treat it aim at the wrong target, according to new research from the Northwestern University Feinberg School of Medicine. The medications are like arrows shot at the outer rings of a bull's eye instead of the center. (...)

- Kan antidepressiva forverre langtidsutviklingen av depresjon

Can Antidepressant Drugs Worsen The Long Term Course Of Depression? (Kan antidepressiva forverre langtidsutviklingen av depresjon)
medicalnewstoday.com 4.10.2011
Some new data emerge from a study published in Progress in Neuro-psychopharmacology and Biological Psychiatry by Giovanni Fava and Emanuela Offidani of the University of Bologna.

There is increasing awareness that, in some cases, long-term use of antidepressant drugs (AD) may enhance the biochemical vulnerability to depression and worsen its long-term outcome and symptomatic expression, decreasing both its likelihood of subsequent response to pharmacological treatment and the duration of symptom-free periods. A review of literature suggesting potential side effects during long treatment with antidepressant drugs was performed. Studies were identified electronically using the following databases: Medline, Cinahl, PsychInfo, Web of Science and the Cochrane Library. (...)

(Anm: The mechanisms of tolerance in antidepressant action. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2011;35(35): 1593-1602 (15 August).)

- Serotonerg ubalanse? (Svindelen som aldri tar slutt)

Study Undermines Case For Antidepressants (Studie undergraver bevis for antidepressiva)
forbes.com 5.1.2010
(...) Såkalte selektive serotoninreopptakshemmere (SSRIer) slik som Seroxat, Prozac og Zoloft, er utstrakt brukt på bakgrunn av teorien om at deprimerte mennesker lider av mangel på hjernekjemikaliet serotonin. Men få harde data støtter det populære konseptet, ifølge Kirsch. "Hele idéen med serotoninmangel er en myte." (...) (So-called selective serotonin reuptake inhibitors such as Paxil, Prozac and Zoloft, gained widespread use on the theory that depressed people suffer from a deficit of the brain chemical serotonin. But little hard data supports the popular concept, Kirsch says. "This whole idea of serotonin deficiency is a myth.")

Det er ikke eksakt kjent hvor mange pasienter med mild depresjon som tar antidepressiva. Men en undersøkelse sitert av forskerne fant at 71 % av alle pasienter som søker behandling for depresjon faller i den mildere kategori, hvor det er sannsynlig at placebo virker like bra. (...) (It is unknown exactly how many patients taking antidepressants have milder cases of depression. But one survey cited by the researchers found that 71% of all patients seeking treatment for depression fall in the milder category, where placebos are likely to do as well.)

(Anm: paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

(Anm: Svindelen som aldri tar slutt (forskning.no 17.4.2004).)

(Anm: Antidepressant Drug Effects and Depression Severity A Patient-Level Meta-analysis. JAMA. 2010;303(1):47-53 (January 6).)

Ads for SSRI antidepressants are misleading, say researchers (Reklamer for SSRI-antidepressiva er villedende, ifølge forskere)
medicalnewstoday.com 12.11.2005
Reklamer for en klasse antidepressiva kalt SSRI-er påstår ofte at depresjon skyldes kjemisk ubalanse i hjerne, og at SSRI-er korrigerer denne ubalansen, men disse påstander er ikke støttet av vitenskapelig bevis, uttaler forskere i PLoS Medicine. (Consumer ads for a class of antidepressants called SSRIs often claim that depression is due to a chemical imbalance in the brain, and that SSRIs correct this imbalance, but these claims are not supported by scientific evidence, say researchers in PLoS Medicine.)

Selv om forskere på 1960-tallet antydet at depresjon kan være linket til lavt nivå av serotonin (den såkalte "serotonin-hypotese"), sier de at forskning hittil har mislykkes å bekrefte hypotesen. (Although scientists in the 1960s suggested that depression may be linked to low brain levels of the chemical serotonin (the so-called "serotonin hypothesis"), contemporary research has failed to confirm the hypothesis, they say.)

Forskerne--Jeffrey Lacasse, doktorgradkandidat Florida State University og dr. Jonathan Leo, professor i neuroanatomi ved Lake Erie College of Osteopathic Medicine--gransket amerikansk forbrukerreklame for SSRI-er publisert i trykte medier, fjernsyn, og internett. De fant mange påstander om at SSRI-er gjenoppretter serotoninbalansei hjernen. "Men likevel er der ikke etablert noe vitenskapelig som tilsier at "balanse" av serotonin korrigeres," ifølge forfatterne. (...) (The researchers--Jeffrey Lacasse, a doctoral candidate at Florida State University and Dr. Jonathan Leo, a neuroanatomy professor at Lake Erie College of Osteopathic Medicine--studied US consumer advertisements for SSRIs from print, television, and the Internet. They found widespread claims that SSRIs restore the serotonin balance of the brain. "Yet there is no such thing as a scientifically established correct 'balance' of serotonin," the authors say.)

(Anm: Serotonin and Depression: A Disconnect between the Advertisements and the Scientific. PLoS Medicine 2005;2:0101-0106 (December 2005). (PDF).)

Debate Simmers Over Popular Antidepressant Ad Claims (healingwell.com) (Debatten koker grunnet reklamepåstander om populær antidepressiva)
healthfinder.gov 28.2.2006
Der er ingen bevis for at depresjon stammer fra en kjemisk ubalanse i hjernen, hevder kritikere. (There's no evidence depression stems from a chemical imbalance in the brain, critics say.)

-- Mange amerikanere har sett TV-reklamer for Pfizers reseptbelagte antidepressiva Zoloft. (...) (-- Many Americans have seen the television ad for Pfizer Inc.'s prescription antidepressant Zoloft.)

Denne type utsagn er formidlet i reklamekampanjer så ofte overfor forbrukere av selektive serotoninreopptakshemmere (SSRI) at kritikere sier at disse påstander nå tilsynelatende oppfattes som en slags vitenskapelig sannhet. (Statements like these have been repeated so often in direct-to-consumer ad campaigns for selective serotonin reuptake inhibitor (SSRI) antidepressants that critics say they now have the ring of scientific truth.)

Derfor kan mange amerikanere "bli svært overrasket over at ikke en eneste artikkel kan fremvises som direkte påviser at depresjon er et resultat av mangel på serotonin," sa Jeffrey Lacasse, en doktorgradsstudent ved Florida State University's College of Social Work. (...) (That's why many Americans "might be particularly surprised that not a single article can be produced which directly demonstrates that depression is the result of a serotonin deficiency," said Jeffrey Lacasse, a doctoral student at Florida State University's College of Social Work.)

Talking therapies are more effective than Prozac-type drugs, says scientist (Samtaleterapi er ifølge forsker mer effektivt enn Prozac og andre liknende legemidler)
timesonline.co.uk 14.6.2010
Antidepressants of the Prozac type are no better than a placebo, a leading psychologist has claimed. According to Irving Kirsch, the evidence is overwhelming that there is no link between depression and serotonin, the brain chemical that such drugs are supposed to affect. (...)

Professor Kirsch’s research, presented at The Times Cheltenham Science Festival, shows that a new drug, tianeptine, is just as effective as SSRIs in treating depression. Tianeptine, which is a serotonin reuptake enhancer, actually decreases the level of the chemical.

I sammenlikninger av tianeptine med SSRI-er og de tidligere trisykliske antidepressiva, produserte de bortimot identiske responsrater: 63 prosent av pasienter responderte på tianeptine, 62 prosent på SSRI-er og 65 prosent på trisykliske. Dersom legemidler som har tre forskjellige effekter på serotonin forårsaker liknende nytte, kan det ikke skyldes deres spesifikke kjemiske aktivitet, uttalte professor Kirsch. “Ideen om at neurotransmitteren serotonin er en kausal faktor i depressjon er feil.” (...) (In comparisons of tianeptine with SSRIs and the earlier tricyclic antidepressants, the three produced virtually identical response rates: 63 per cent of patients responded to tianeptine, 62 per cent to SSRIs and 65 per cent to tricyclics. If drugs having three different effects on serotonin brought similar benefits, these could not be due to their specific chemical activity, Professor Kirsch said. “The idea that the neurotransmitter serotonin is a causal factor in depression is wrong.”)

- SSRI-preparater reorganiserer hjernens plastisitet

Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine (Destabiliserende atferd forårsaket av den selektive serotoninreopptakshemmeren (SSRI-en) fluoxetine (Prozac))
Molecular Brain 2011, 4:12 doi:10.1186/1756-6606-4-12 (16 March)
Background Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat mood and anxiety disorders. However, neuronal bases for both beneficial and adverse effects of SSRIs remain poorly understood. We have recently shown that the SSRI fluoxetine can reverse the state of maturation of hippocampal granule cells in adult mice. The granule cell "dematuration" is induced in a large population of granule cells, and greatly changes functional and physiological properties of these cells. Here we show that this unique form of neuronal plasticity is correlated with a distinct change in behavior of mice. (...)

Conclusions Our results demonstrate that the SSRI fluoxetine can induce marked day-to-day changes in activity levels of mice in the familiar environment, and that the dematuration of the hippocampal granule cells is closely associated with the expression of this destabilized behavior. Based on these results, we propose that the granule cell dematuration can be a potential cellular basis underlying switching-like changes in the behavioral state associated with SSRI treatments. (...)

Depression Drugs -- SSRIs -- May Reorganize Brain Plasticity, New Research Suggests (Legemidler mot depresjon -- SSRI-er -- kan ifølge ny forskning reorganisere hjernens plastisitet)
sciencedaily.com 18.3.2011
ScienceDaily (Mar. 18, 2011) — Selective serotonin reuptake inhibitors (SSRI) such as Prozac are regularly used to treat severe anxiety and depression. They work by immediately increasing the amount of serotonin in the brain and by causing long term changes in brain function. However it can take weeks of treatment before a patient feels any effect and both beneficial effects and side effects can persist after treatment is stopped.

New research published by BioMed Central's open access journal Molecular Brain investigates physiological changes within the brain that may be caused by SSRI treatment.

The hippocampus is an area of the brain involved in long term memory and spatial awareness, and is involved in symptoms afflicting people with Alzheimer's disease, such as loss of memory and disorientation. Neuronal cells in the hippocampus can change their activity and strength of connections throughout life, a process known as plasticity, which thought to be one of the ways new memories are formed. Altered plasticity is often associated with depression and stress.

Researchers from the Department of Pharmacology, Nippon Medical School, showed that chronic treatment of adult mice with fluoxetine (Prozac) caused changes to granule cells, one of the main types of neuronal cells inside the hippocampus, and to their connections with other neuronal cells. The granule cells appeared to undergo serotonin-dependent 'dematuration', which increased their activity and reversed adult-type plasticity into an immature state. These changes to the cell's plasticity were associated with increased anxiety and in alternating between periods of hyper or hypo activity.

Katsunori Kobayashi explained, "Some of the side effects associated with Prozac in humans, such as anxiety and behavioral switching patterns, may be due to excessive dematuration of granule cells in the hippocampus." (...)

Prozac reorganizes brain plasticity (Prozac reorganiserer hjernens plastisitet)
eurekalert.org 15.3.2011e
Selective serotonin reuptake inhibitors (SSRI) such as Prozac are regularly used to treat severe anxiety and depression. They work by immediately increasing the amount of serotonin in the brain and by causing long term changes in brain function. However it can take weeks of treatment before a patient feels any effect and both beneficial effects and side effects can persist after treatment is stopped. New research published by BioMed Central's open access journal Molecular Brain investigates physiological changes within the brain that may be caused by SSRI treatment.

The hippocampus is an area of the brain involved in long term memory and spatial awareness, and is involved in symptoms afflicting people with Alzheimer's disease, such as loss of memory and disorientation. Neuronal cells in the hippocampus can change their activity and strength of connections throughout life, a process known as plasticity, which thought to be one of the ways new memories are formed. Altered plasticity is often associated with depression and stress.

Researchers from the Department of Pharmacology, Nippon Medical School, showed that chronic treatment of adult mice with fluoxetine (Prozac) caused changes to granule cells, one of the main types of neuronal cells inside the hippocampus, and to their connections with other neuronal cells. The granule cells appeared to undergo serotonin-dependent 'dematuration', which increased their activity and reversed adult-type plasticity into an immature state. These changes to the cell's plasticity were associated with increased anxiety and in alternating between periods of hyper or hypo activity.

Katsunori Kobayashi explained, "Some of the side effects associated with Prozac in humans, such as anxiety and behavioral switching patterns, may be due to excessive dematuration of granule cells in the hippocampus." (...)

(Anm: Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine (Destabiliserende atferd forårsaket av den selektive serotoninreopptakshemmeren (SSRI-en) fluoxetine (Prozac)). Molecular Brain 2011, 4:12 (16 March).)

A New Troublesome Long-Term Effect Of Antidepressant Drugs; Tardive Dysphoria (En ny plagsom langtidseffekt av antidepressiva, tardive dysfori)
medicalnewstoday.com 8.3.2011
(...) A possible prodepressant effect of antidepressants has been previously proposed. Fava was the first to suggest that an antidepressant-related neurobiochemical mechanism of increasing vulnerability to depression might play a role in worsening the long-term outcome of the illness. Understanding of potential mechanisms of this phenomenon can be gleaned from observations regarding the short form of the serotonin transporter (5HTTR). Patients with the short form of the 5HTTR and prolonged antidepressant exposure, may be particularly vulnerable to antidepressant-related worsening. In other words, prolonged exposure to antidepressants can induce neuroplastic changes that result in the genesis of antidepressant-induced dysphoric symptoms. The investigators propose the term 'tardive dysphoria' to describe such a phenomenon and describe diagnostic criteria for it. Tapering or discontinuing the antidepressant might reverse the dysphoric state. Antidepressant discontinuation may not provide immediate relief. In fact, it is likely that transient symptoms of withdrawal will occur in the initial 2-4 weeks following antidepressant discontinuation or tapering. However, after a prolonged period of antidepressant abstinence, one may see a gradual return to the patient's baseline. (...)

(Anm: Antidepressants: Tardive dysphoria in an elderly patient?: case report. Journal of Psychotherapy and Psychosomatics 2011 (January 29).)

Langvarig udsættelse for antidepressiva kan fremkalde tardive Dysfori
news-medical.net/news.com 9.3.2011
I den aktuelle udgave af psykoterapi og Psykosomatik en ny vigtig bivirkning af antidepressiv medicin er beskrevet: tardive dysfori.

Behandling-resistent depression (TRD) kan være relateret til utilstrækkeligt dosering af antidepressiva eller antidepressiv tolerance. Alternativt er der grund til at tro, at antidepressiv behandling selv kan bidrage til en kronisk depressiv syndrom. Denne undersøgelse rapporterer et tilfælde af antidepressiv ophør i en TRD patient, en 67-årig hvid mand med pludseligt opstået major depressiv sygdom i en alder af 45 år. (...)

Are Psychiatric Medications Causing More Mental Illness? (Forårsaker psykiatriske legemidler mer psykisk sykdom?)
radioboston.wbur.org 19.1.2011
According to some sources, the use of psychiatric drugs like ritalin, prozac and xanax, has doubled in the last decade

A local science journalist and author, Robert Whitaker, says in his recent book, “Anatomy of an Epidemic: Magic Bullets, Psychiatric Durgs, and the Astonishing Rise of Mental Illness in America,” that the long-term use of these popular psychiatric medications is actually causing more mental illness — not less.

Whitaker says his research which examines for the first time the long-term effects of psychiatric drugs, shows that these medications are often making diseases such as depression and schizophrenia worse, not better. He points to a major increase in the number of people getting federal disability benefits for mental illness who are taking these medications as a sign that the drugs are, in fact, contributing to chronic mental illness in America. For example, Whitaker points out that between 1987 and 2007, “the number of disabled mentally ill children rose thirty-five fold.”

Whitaker’s claims are refuted by reputable members of the psychiatric community here in Boston. (...)

SSRI versus placebo

Why Antidepressants Don't Live Up to the Hype
time.com 6.5.2009
In the '90s, Americans grew fond of the idea that you can fix depression simply by taking a pill — most famously fluoxetine (better known as Prozac), though fluoxetine is just one of at least seven selective serotonin reuptake inhibitors (SSRIs) that have been prescribed to treat hundreds of millions of people around the world. (...)

Meta-analysis of the placebo response in antidepressant trials.
J Affect Disord. 2009 Feb 25. [Epub ahead of print]
Improvements in placebo groups of antidepressant trials account for a major part of the expected drug effects. We aimed to determine overall effect sizes of placebo and drug effects in antidepressant trials, and to analyze whether the placebo effect in antidepressant trials also occurs for patient self-perception, general psychopathology, and quality of life. (...)

CONCLUSIONS The placebo effect accounted for 68% of the effect in the drug groups. Whereas clinical trials need to control the placebo effect, clinical practice should attempt to use its full power. (...)

The Powerful Placebo: From Ancient Priest to Modern Physician (Den sterke placebo: Fra gammel prest til moderne lege)
Arthur K. Shapiro, M.D & Elaine Shapiro PH. D. 1997, ISBN 0-8018-55691-I)
En alvorlig reservasjon angående gyldigheten av disse og andre kontrollerte legemiddelstudier er at uvirksom placebo er brukt i stedet for aktiv placebo som etterlikner sideeffekter av det eksperimentelle legemidlet som blir evaluert (Blumenthal et al 1974). (A serious reservation about the validity of these and other controlled studies of drugs is that inert placebos were used instead of active placebo that mimic the side effects of the experimental drug being evaluated (Blumenthal et al 1974). (...)

Et stadig voksende materiale viser at når aktiv placebo blir brukt i kontrollerte studier for antidepressiva og andre legemidler, er det aktive legemidlet knapt bedre enn placebo, hvis det, i det hele tatt, er bedre enn placebo. (...) (A growing literature demonstrates that if active placebo controls are used in studies of antidepressant and other drugs, the active drug is only slightly, if at all, better than placebo.)

The use of placebo controls (Bruk av placebo som kontroll)
N Engl J Med 1995;332:62
Av de 14 effektstudier utført før FDA godkjente bruken av Prozac (fluoxetine) viste kun 5 av disse at Prozac statistisk var overlegen placebo. (...) (Of the 14 efficacy studies conducted before the FDA approved the use of Prozac (fluoxetine) only 5 showed Prozac to be statistically superior to placebo.)

(Anm: FDAs Summary basis of approval: NDA 18-936 (Prozac). Rockville. Md.: Food and Drug Administration, oktober, 1988. (Oppsummerende grunnlag for godkjennelse).)

Novo Nordisk” (paroksetin): Nytt ikke-tricyklisk antidepressivum
Setekleiv J.
Nytt fra Statens legemiddelkontroll 1993;16(2):8-9)
I åtte av tretten placebokontrollerte studier ble det konkludert med at paroksetin hadde bedre antidepressiv effekt enn placebo. I de øvrige fem studiene var det ingen signifikant forskjell. I seksten studier med aktiv kontroll over seks uker ble paroksetin funnet likeverdig med de øvrige antidepressiva. Paroksetin ble sammenlignet med imipramin i seks av studiene, med amitriptylin i fire, klomipramin i to, og mianserin i fire studier. I én undersøkelse var paroksetin bedre enn imipramin, i to studier ga henholdsvis imipramin og klomipramin bedre effekt enn paroksetin. (...)

(Anm: I praksis innebærer dette at to av de mest omsatte SSRI-preparater i 14 av 27 (52%) studier ikke kom bedre ut enn placebo: Dette til tross for at forskning viser at studier som er finansiert av legemiddelfirmaer generelt favoriserer legemidlene.)

Can the Placebo Treat Depression? That Depends (Kan placebo behandle depresjon? Det kommer an på)
New York Times. 25.06.2002
(...) I en studie som snart blir publisert, analyserte dr Arif Khan, en psykiater ved Northwest Clinical Research Center i Washington, Food and Drug Administrations database for 52 kiniske forsøk på depresjon, som involverte ni nye antidepressiva, utført fra 1985 til 2000. Siden byrået krever at legemiddelfirmaene rapporterer alle data fra alle studier for legemidler under utvikling, kan databasen gi et mer nøyaktig bilde av nye legemidlers effektivitet enn medisinske tidsskrifter, hvor positive resultater er langt mer sannsynlig å bli rapportert enn de negative. (In a soon to be published study, Dr. Arif Khan, a psychiatrist at the Northwest Clinical Research Center in Washington, analyzed the Food and Drug Administration's database of 52 clinical trials in depression, involving nine new antidepressants, conducted from 1985 to 2000. Since the agency requires drug companies to report all data from all studies for drugs under development, the database can give a more accurate picture of a new drug's efficacy than the medical journals, where positive findings are far more likely to be reported than negative ones.)

Dr. Khan fant at i bare 48 prosent av de 52 kliniske forsøk var antidepressiva overlegen placebo. Betyr dette virkelig at antidepressiva gjennomsnittlig ikke er bedre enn placeboer for depresjon? (...) (Dr. Khan found that in only 48 percent of the 52 clinical trials was the antidepressant superior to the placebo. Does this really mean that antidepressants are on average no better than placebos for depression?)

(Anm: Placebo response and antidepressant clinical trial outcome. J Nerv Ment Dis. 2003;191:211-8.)

Listening to Prozac but Hearing Placebo: A Meta-Analysis of antidepressant Medication (Lytt til Prozac men hør på placebo: En metaanalyse av antidepressiv medikasjon)
Prevention & Treatment 1998;1:1-17 (26.06.1998)
Størrelsen på effekten for de aktive legemidler, som ikke er ansett å skyldes antidepressiva, var like så stor som de klassifisert som antidepressiva, og i begge tilfeller, produserte inaktiv placebo en forbedring som var 75% av effekten for det aktive legemidlet. Disse data øker muligheten for at den tilsynelatende legemiddeleffekt (25% av legemiddelreaksjonen) i virkeligheten er en aktiv placebo effekt. Granskning av størrelsen på før-etter-effekt blant depressive personer, som ble anvist til ikke-behandling eller venteliste-kontrollgrupper, tyder på at omtrent en fjerdedel av legemiddelresponsen er på grunn av den aktive medisinering, halvdelen er en placebo effekt, og den gjenstående fjerdedel på grunn av andre uspesifikke faktorer. (...) (The effect size for active medications that are not regarded to be antidepressants was as large as that for those classified as antidepressants, and in both cases, the inactive placebos produced improvement that was 75% of the effect of the active drug. These data raise the possibility that the apparent drug effect (25% of the drug response) is actually an active placebo effect. Examination of pre–post effect sizes among depressed individuals assigned to no-treatment or wait-list control groups suggest that approximately one quarter of the drug response is due to the administration of an active medication, one half is a placebo effect, and the remaining quarter is due to other nonspecific factors.)

Yes, There Is a Placebo Effect, but Is There a Powerful Antidepressant Drug Effect? (Ja, der er en placebo effekt, men er der en sterk antidepressiv legemiddeleffekt?)
Prevention & Treatment 2002; 5:1-8
journals.apa.org (15.07.2002)
Da Guy Sapirstein og jeg foretok vår meta-analysis (Kirsch & Sapirstein, 1998), tvilte vi ikke på at antidepressiva er farmakologiske effektive. Vår intensjon var å evaluere placeboeffekten. Resultatat av analysen overasket oss. Vi forventet en virkelig placeboeffekt, men vi forventet ikke en slik liten medikamenteffekt. (...) (When Guy Sapirstein and I undertook our meta-analysis (Kirsch & Sapirstein, 1998), we did not doubt that antidepressants are pharmacologically effective. Our intent was to evaluate the placebo effect. The results of that analysis surprised us. We expected a substantial placebo effect, but we did not expect such a small medication effect.)

Placebo response in depression: bane of research, boon to therapy (Placebo respons ved depresjon: forbannelse for forskning, velsignelse for terapi)
Andrews G.
Br J Psychiatry. 2001;178:192-4
publisert i British journal of Psychiatry, hvor det blant annet heter at “Noen ganger mislykkes antidepressiva, og for den del kognitiv atferdsterapi, å vise en positiv effekt ovenfor placebo, ganske enkelt fordi behandlingene ikke er spesielt virksom i forhold til forandringer i kontrollgruppen for placebo. (Sometimes antidepressant drugs, and for that matter cognitive-behavioural therapies, fail to show superiority over placebo, simply because the treatments are not very powerful compared with the change in the placebo control group.)

Andre (Quality Assurance Project, 1983; Joffe et al, 1996) hadde konstatert at størrelsen på den fremgangen som ble tillagt placebogruppen i depressive forsøk var større enn den ekstra framgang som ble tillagt legemidler, således representerer ikke resultatet noe nytt. Hva som var nytt var at korrelasjonen på 0,9 mellom placeboeffekten og legemiddeleffekten indikerte at praktisk talt alt avvik i reaksjon mellom forbedringen i de legemiddelbehandlede grupper i de ulike studier kunne forutses av reaksjonen hos personer randomisert til placebogrupper. (...) (Others (Quality Assurance Project, 1983; Joffe et al, 1996) had noted that the size of the progress attributed to the placebo group in depression trials was greater than the additional progress attributed to the drugs, so the finding is not new. What was new was that the correlation of 0.9 between the placebo effect and drug effect indicated that virtually all the variation between the improvement in the drug-treated groups in the different trials could be predicted by the response in the subjects randomised to the placebo groups.)

Moncrieff et al (1998), tok opp dette i en liten metaanalyse på 9 studier og fant at overlegenheten for legemidlet ovenfor det aktive placeboet atropine ble redusert fra 0,50 i undersøkelser på ikke-aktiv placebo til en effekt på 0,21 for aktiv placebo, i overensstemmelse med Kirsch & Sapirstein forslag om at mennesker i undersøkelser responderer mer positivt dersom de erfarer sideeffekter. (...) (Moncrieff et al (1998), in a small meta-analysis of nine studies, addressed this and found that the superiority of drug over the active placebo atropine was reduced from an effect size of 0.50 in non-active placebo trials to an effect size of 0.21 with active placebos, consistent with the Kirsch & Sapirstein suggestion that people in trials respond more positively if they experience side-effects.)

Kendler et al (1997) studerte et befolkningsutvalg av kvinner og fant at median tiden for helbredelse var 6 uker, med 75% helbredelse etter 12 uker. Dersom tiden for helbredelse i befolkningen er 8 uker og 75% blir helbredet etter 16 uker, da vil mennesker rekruttert i forsøk etter å ha vært deprimert i 8 uker ha 50% risiko til å komme seg i løpet av utførelsen av det vanligvis 8-uker lange forsøket. Disse to faktorer, respons på oppmuntring og en 50% sannsynlighet for spontan bedring i løpet av forsøket, kan redegjøre for den betydelige fremgangen for placebo kontrollgrupper i depresjonsforsøk. (...) (Kendler et al (1997) studied a population sample of women and found a median time to recovery of 6 weeks, with 75% recovering in 12 weeks. If the population time to recovery were a median of 8 weeks and 75% recovered within 16 weeks, then people recruited into a trial after being depressed for 8 weeks would have a 50% chance of remitting during the conduct of the usual 8-week trial. These two factors, response to encouragement and a 50% probability of spontaneous remission during the trial, could account for the considerable progress of placebo control groups in depression trials.)x (ref The prediction of length of major depressive episode: results from an epidemiological survey of female twins. Psycological Medicine;1997:107-7.)

From Placebo to Panacea: Putting Psychiatric Drugs to the test
NEJM1998;339:275
En kritisk gjennomgåelse av psykoaktiv-legemiddellitteratur, påstår at der i alt vesentlig er en utilstrekkelig vitenskapelig informasjon til å konkludere at psykoaktive legemidler er vesentlig mer effektive enn placeboer. (...) (A critical review of the psychoactive-drug literature, it asserts essentially that there is inadequate scientific information to conclude that psychoactive drugs are substantially more effective than placebos.)

Med hensyn til legemidler brukt til å behandle barn, konkluderer Rhonda L. Fisher and Seymour Fisher, ”Det er ikke en overdrivelse å hevde, alt i alt, at psykofarmakaterapi for et segment av ungdommer i befolkningen er vitenskapelig uforsvarlig. Leger som forskriver ”psykotrope legemidler mot depressiv og engstelse symptomatologi gjør dette uten rasjonell støtte. (With regard to drugs used to treat children, Rhonda L. Fisher and Seymour Fisher conclude, "It is not an exaggeration to assert that, by and large, the psychopharmacotherapy of the youth segment of the population is scientifically unjustified." Physicians who prescribe "psychotropic drugs for depressive and anxiety symptomatology are doing so without rational support.)

Bokens budskap er sjokkerende og nihilistisk med hensyn til legemiddelterapier, men dersom det får oss til å reflektere i vår praksis, vil forfatterne ha gitt et viktig bidrag. (The book's message is shocking and nihilistic regarding drug therapies, but if it makes us reflect on our practices, the authors will have made an important contribution.)

(Anm: From Placebo to Panacea: Putting Psychiatric Drugs to the test (Fra placebo til pancea: Testing av psykiatriske legemidler). Seymour Fisher, Roger P. Greenberg. New York: John Wiley, 1997. ISBN 0-471-14848-2.)

Penetrating the blind in a study of an SSRI (Bryting av blindheten i en studie av en SSRI)
J Behav Ther Exp Psychiatry 2002;33:67-71
Vi vurderte blind integritet in en dobbeltblindet studie som sammenliknet paroxetine 20 mg med uvirksom placebo hos 20 frivillige som forsøkte å slutte med metamfetamin. På slutten av studien, gjennomgikk de blindede klinikere diagrammene og forsøkte å identifisere de utpekt tilstander for de 13 kasus som fullførte mer enn uker av studien. De tre kasus som fullførte hele studien forsøkte også å identifisere sine tilstander på et spørreskjema. Vi konkluderte at blindheten uforvarende kan bli brutt når behandlingene som studeres er placebo og den selektive serotonin reopptakshemmeren (SSRI) paroxetine. Rettskaffenheten for blindheten bør testes i alle dobbeltblindede SSRI-studier. (...) (We assessed blind integrity in a double-blinded study comparing paroxetine 20 mg with inert placebo in 20 volunteer subjects who were attempting to stop using methamphetamines. At the end of the study, the blinded clinicians reviewed subject charts and attempted to identify the assigned conditions for the 13 subjects who completed two or more weeks of the study. The three subjects who completed the entire study also attempted to identify their conditions on a questionnaire. We conclude that the blind may unwittingly be broken when the treatments under study are placebo and the selective serotonin reuptake inhibitor (SSRI) paroxetine. The integrity of the blind should be tested in all double-blind SSRI studies.)

(Anm: paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

The validity of ”identical matching placebos” (Gyldigheten av ”identiske matchende placebos”)
Arch Gen Psychiatry 1974;31:214-5)
Denne studien var en laboratorie-simulering av en dobbel blindet klinisk studie hvor inaktive kontroll-legemidler for kontroll er beskrevet som “identiske matchende placeboer. For fem av seks legemiddelkategorier skjelnet personer som simulerte eksperimentatorer eller pasienter signifikant (P 0,001) mellom aktivt legemiddel og placebo basert på fysiske særpreg ved medisineringen. På denne måte er at mange av de identisk matchende placebo faktisk ikke identiske men var forskjellig fra aktive legemidler i fysiske egenskaper slik som tekstur, farge, og tykkelse. (...) (This study was a laboratory simulation of the double-blind clinical study in which inactive control drugs are described as “identical matching placebos. For five of six drug categories, subjects simulating experimenters or patients significantly (P 001) differentiated active drug from placebo based on physical characteristics of the medications. Thus, many of the identical matching placebos were not in fact identical but were different from the active drug in physical properties such as texture, color, and thickness.)

Resulatet tyder på at antagelsen om at "identisk matchende placeboer’, som brukes i en studie bør testes ved innledende sammenligning av placebo med aktivt legemiddel. Viktige anbefalinger er at aktivt legemiddel og kontroll blir administrert som kapsler. At forskningsassistenter er minst mulig kjent med det eksperimentelle design av studien, at Federal Drug Administration eller National Institutes of Health formular for standard kapsler i kontrollerte kliniske evalueringsstudier brukes, og at placebo inneholder aktive ingredienser for å mimikere effekten av det aktive legemidlet. (The results suggest that the assumption that "identical matching placebos', as used in a study should be tested by preliminary comparison of the placebo with the active drug. Major recommendations are that active drug and control be administered as capsules. That research assistants be minimally aware of the experimental design of the study, that the Federal Drug Administration or National Institutes of Health formulate standard capsules for use in controlled clinical evaluation studies, and that the placebo contain active ingredients to mimic the side effects of the active drug.)

Placebo response and antidepressant clinical trial outcome (Respons på placebo og resultater for antidepressiva)
J Nerv Ment Dis. 2003;191:211-8)
Kun 21,1% av antidepressiv behandling i forsøk med høy placeborespons (> 30 % gjennomsnittlig forandring fra bais) viste statistisk overlegenhet over placebo sammenliknet med 74,2 % i forsøk med lav placeborespons (< eller =30).” (Only 21.1% of antidepressant treatment arms in trials with high placebo response (>30% mean change from baseline) showed statistical superiority over placebo compared with 74.2% in trials with a low placebo response (< or =30).) (...)

An application of the revised CONSORT standards to FDA summary reports of recently approved antidepressants and antipsychotics
Biol Psychiatry 2002;52:62-7
En anvendelse av reviderte CONSORT standarder fra FDA sammendragrapporter for nylige godkjente antidepressiva og antipsykotika) (CONSORT: Consolidated Standards of Reporting; konsoliderte standarder for rapportering; utviklet for å bedre kvaliteten på artikler som beskriver randomiserte forsøk)

Bakgrunn: De senere år er der blitt introdusert mange antidepressiva og antipsykotika. Typisk for disse substanser er at de er basert på publiserte positive kliniske forsøk; imidlertid, utarbeider Food and Drug Administration (FDA) rapporter med sammendrag av alle sentrale randomiserte kliniske forsøk, som er tilgjengelig for offentlig gjennomgåelse under Freedom of Information Act. De er sjelden brukt men kan ha offentlig nytte. På denne måte vurderte vi disse rapportene for å evaluere om de kliniske data data kan brukes til å sammenligne psykotrope legemidler. (Background: Recent years have seen the introduction of many antidepressants and antipsychotics. Typically, efficacy of these agents is based on published positive clinical trials; however, the Food and Drug Administration (FDA) compiles summary reports of all pivotal randomized clinical trials, which are available for public review under the Freedom of Information Act. They are rarely accessed but may have public health utility. Thus, we assessed these reports to evaluate if the clinical data can be used for comparing psychotropics.)

Metode: Vi gransket FDA rapportsammendrag for 58 sentrale forsøk for 10 antidepressiva og 7 sentrale forsøk for tre antpsykotika godkjent i USA mellom 1985 og 1998. Vi evaluerte hver enkelt FDA rapport basert på kriterier utledet fra de nylig reviderte Consolidated Standards of Reporting Trials (CONSORT standards) lagt frem av Journal of the American Medical Association for å forbedre randomisere kliniske forsøksrapporter. (Methods: We examined FDA summary reports of 58 pivotal trials from 10 antidepressants and 7 pivotal trials from three antipsychotics approved in the United States between 1985 and 1998. We evaluated each FDA report based on criteria derived from the recently revised Consolidated Standards of Reporting Trials (CONSORT standards) proposed by the Journal of the American Medical Association to improve randomized clinical trial reports.)

Resultater: Samlet, møtte FDA rapporter forsøk på antidepressiva og antipsykotika 38,1 % av CONSORT kriterier tilfredsstillende. Blant antidepressva rapporter, møtte 36,7 % tilfredsstillende CONSORT criteria sammenlignet med 49,0 % blant antipsykotiske legemiddel rapporter. Omfanget som møtte CONSORT kriterier har økt over de siste 15 årene; 21,0 % for de godkjent mellom 1985 og 1989, 37,8% for de mellom 1990 og 1994, og 40,5 % for de mellom 1995 og 1998. (Results: Overall, the FDA reports of antidepressant and antipsychotic trials adequately met 38.1% of the CONSORT criteria. Among the antidepressant reports, 36.7% adequately met CONSORT criteria compared with 49.0% among the antipsychotic reports. The proportions meeting CONSORT criteria have increased over the past 15 years; 21.0% for those approved between 1985 and 1989, 37.8% for those between 1990 and 1994, and 40.5% for those between 1995 and 1998.)

Konklusjoner: FDAs store og omfattende offentlige tilgjengelige oppsummeringsrapporter kan gi en balansert oversikt over forsøksdata fra kliniske studier. Med mindre endringer i klargjøringen av rapportering ved bruk av CONSORT eller lignende retningslinjer vil dataene bli enda mer verdifulle. (Conclusions: The large and inclusive public domain FDA summary reports may provide balanced efficacy clinical trial data. With minor changes in the preparation of reporting by using CONSORT or similar guidelines, the data would be even more valuable.)

- They describe these effects as a "nightmare" and like "torture."

Antidepressants Now No. 1 Drug Prescribed For Women 18-44
nbc4.com 16.11.2007
High Number Of Prescriptions Worrying Some Experts (...)

But not everyone is so lucky. In fact, about two-thirds of people on these drugs experience side effects, which can be severe and devastating.

Internet bloggers are even sharing their experiences with antidepressants online. They describe these effects as a "nightmare" and like "torture." Common reactions include "weight gain, decreased sex drive and severe stomach cramping."

"Something is going on with these drugs," Zuckerman said. "Not everybody metabolizes them the same way. It doesn't have the same effect on every person and some people are harmed by them."

Casalihno is now exercising to combat her depression. She says a pill wasn't the answer for her.

"I was overloaded with everything and I wasn't really addressing the root of the problems," Casalihno said. (...)

- The researchers found that assignment to sertraline did not improve symptoms or wellbeing or length of life (survival) compared with placebo

Screening Heart Patients for Depression Not Effective, Says Study (Screening av hjertepasienter for depresjon ikke effektivt, ifølge studie)
about.com 18.11.2008
In a study which appeared in the November 12 issue of the Journal of the American Medical Association, researchers questioned the American Heart Association's recent suggestion that heart patients be automatically screened for depression.

Dr. Brett Thombs, of McGill and the affiliated Jewish General Hospital, and Dr. Roy Ziegelstein, of Johns Hopkins, said there was not enough evidence to support this "massive, expensive and labor-intensive undertaking." The doctors then went even further and presented evidence that depression testing would not benefit heart patients. (...)

Use of antidepressants for depression in patients with advanced cancer (Bruk av antidepressiva mot depresjon hos pasienter med fremskreden kreft)
Lancet Oncology 2007; 8:567-568
(...) In this issue of The Lancet Oncology, Stockler and colleagues⁴ report on the Zoloft's Effects on Symptoms and survival Time (ZEST) trial, a randomised, placebo-controlled trial comparing the usefulness of an antidepressant with that of placebo in patients with advanced cancer.⁴ This study focused on the care of ambulatory patients with advanced cancer who self-report that they are bothered by at least moderate-intensity depressed mood, anxiety, or fatigue. The researchers found that assignment to sertraline did not improve symptoms or wellbeing or length of life (survival) compared with placebo. (...)

Depression screening and patient outcomes in cardiovascular care: a systematic review (Screening av depressjon og behandlingsresultater ved hjerte- og karsykdommer)
JAMA. 2008 Nov 12;300(18):2161-71.
CONTEXT: Several practice guidelines recommend that depression be evaluated and treated in patients with cardiovascular disease, but the potential benefits of this are unclear. OBJECTIVE: To evaluate the potential benefits of depression screening in patients with cardiovascular disease by assessing (1) the accuracy of depression screening instruments; (2) the effect of depression treatment on depression and cardiac outcomes; and (3) the effect of screening on depression and cardiac outcomes in patients in cardiovascular care settings. (...)

CONCLUSIONS: Depression treatment with medication or cognitive behavioral therapy in patients with cardiovascular disease is associated with modest improvement in depressive symptoms but no improvement in cardiac outcomes. No clinical trials have assessed whether screening for depression improves depressive symptoms or cardiac outcomes in patients with cardiovascular disease. (...)

- Antidepressiva linket til hjertedød

'Lykkepiller' kan give hjertestop
videnskab.dk 24.11.2011
Det populære antidepressive middel Cipramil kan ifølge et nyt studie få hjertet til at slå ude af takt, så det i sjældne tilfælde går i stå. Lægemiddelstyrelsen ændrer nu sine anbefalinger til brugen af 'lykkepillerne'.

(Redaktionel note, 24. november 2011: Nyheden om det amerikanske studie har hurtigt fået mange patienter til at blive bekymrede for, om de skal holde op med at tage deres medicin. Lægemiddelstyrelsen beder i den forbindelse om, at man ikke ringer til styrelsen, men taler med sin egen læge, hvis man er usikker på sin medicin. Lægemiddelstyrelsen understreger samtidig, at det er sundhedsfarligt at holde op med at tage sin medicin uden lægens anbefaling.)

Et nyt amerikansk studie har for nylig afsløret en hidtil ukendt potentiel farlig bivirkning ved Cipramil, som mange depressive danskere for øjeblikket bliver behandlet med. Omkring 178.000 danskere er i behandling med Cipramil og kopiudgaverne af dette lægemiddel, der alle rummer det virksomme stof Citalopram. (...)

Det kan undre, hvorfor man ikke fra begyndelsen undersøgte, om lægemidlet havde denne effekt, men Lundbecks pressechef Mads Kronborg fortæller, at man ikke tidligere har været opmærksom på mekanismen, da indrapporteringerne fra læger og patienter i årenes løb ikke viser nogen tegn på, at der skulle være en forhøjet risiko. (...)

Dansk Psykiatrisk Selskab og Dansk Kardiologisk Selskab har netop behandlet dette spørgsmål og andre problemer med medicinen i en fælles rapport. (...)

Antidepressants linked to cardiac death (Antidepressiva linket til hjertedød)
hospitalpharmacyeurope.com 16.11.2011
People taking anti-psychotic drugs and anti-depressant drugs have a much higher risk of dying during an acute coronary event of a fatal arrhythmia than the rest of the population, according to research published in the European Heart Journal.

The study showed that the combined use of both antipsychotic and antidepressant drugs was associated with an even greater risk of sudden cardiac death (SCD) during a coronary event. (...)

(Anm: Antidepressant medication use and future risk of cardiovascular disease: the Scottish Health Survey. Eur Heart J (2011) 32 (4): 437-442 (November 30).)

Høye doser citalopram kan gi hjertebivirkninger
legemiddelverket.no 8.11.2011
Det er påvist sammenheng mellom høye doser citalopram og hjertebivirkninger. Ny maksimaldose for citalopram er 40 mg.

Citalopram brukes for å behandle depresjoner, panikkangst og tvangslidelse. En gjennomgang av studier og spontanrapporter viser er en sammenheng mellom bruk av høye doser citalopram og forlenget QT-intervall ved EKG. (...)

Daily Mail: - Liv ødelagt av lykkepiller

Lives destroyed by happy pills: As our use of antidepressants DOUBLES in a decade, experts say thousands are being given dangerous drugs they don't need (Liv ødelagt av lykkepiller: Idet vårt forbruk av antidepressiva DOBLES på et tiår, sier eksperter at tusener er gitt legemidler de ikke trenger)
dailymail.co.uk 29.6.2010
(...) After about six weeks she went to see her doctor, who diagnosed depression and anxiety. 'I asked him if he was sure, because there were other symptoms such as diarrhoea, weight-loss and vomiting. But he confirmed his diagnosis and prescribed an antidepressant.' (...)

Unfortunately this only made her feel worse; she developed the shakes as well as suicidal thoughts. In an attempt to remedy this, her GP changed the medication three weeks later. But nothing changed.
And after mentioning her suicidal thoughts to her doctor, she was put under the supervision of a mental health team.

Six weeks later, Clare was put on yet another antidepressant, along with a tranquilliser and an anti-psychotic drug. She was now sleeping 14 hours a day; unable to work, she had to rely on her boyfriend for support.

'I was zombified, but still felt the anxiety and the terror, and that didn't seem right. However, my doctor simply increased my dose.' (...)

'The only good part was a brilliant nurse, who took me seriously when I said I'd always felt that something physical had caused my symptoms and put me in touch with a sympathetic private doctor,' she says.

A year-and-a-half after her symptoms began, Clare was diagnosed with an overactive thyroid and a problem with her adrenal glands. 'That was why I had been so bizarrely agitated, had diarrhoea and had lost weight.' (...)

Clare's story is extreme, but it is far from unique. Increasing numbers of Britons are taking antidepressant drugs, with prescriptions doubling over the past ten years, according to a report this month. In 2000, there were 20 million prescriptions - this rose to 39 million last year.

While this rise is partly being blamed on the recession, experts are concerned that misdiagnosis is a major factor. Indeed, a study published recently in The Lancet found that the average GP will wrongly diagnose 16 out of every 100 patients they see with depression and anxiety. (...)

SSRI-er: Ingen kost-nytteverdi i primærhelsetjenesten

Cost-Effectiveness of a Disease Management Program for Major Depression in Elderly Primary Care Patients.
J Gen Intern Med. 2006 (Jul 7)
BACKGROUND: Major depression is common in older adults and is associated with increased health care costs. Depression often remains unrecognized in older adults, especially in primary care. OBJECTIVE: To evaluate the cost-effectiveness of a disease management program for major depression in elderly primary care patients compared with usual care. (...)

INTERVENTIONS: General practitioners in the intervention group received training on how to implement the disease management program consisting of screening, patient education, drug therapy with paroxetine, and supportive contacts. General practitioners in the usual care group were blind to the screening results. Treatment in this group was not restricted in any way. (...)

KONKLUSJONER: Dette sykdomsprogrammet for behandling av alvorlig depresjon hos eldre i primærhelsetjenesten hadde ingen statistisk signifik