freakoutcrazy

Blog des AK Psychiatriekritik der NFJ Berlin

Kategorie: Seroquel

Enough is Enough Series: 2-Year-olds on Anti-psychotics and Biological Markers for Psychosis

What is so disturbing about this destructive belief system leads right to the second article, “Still in a crib, Yet being Given Antipsychotics,” by Alan Schwarz in the New York Times, December 10, 2015. In fairness to the writer, he seems rather appalled himself. 20,000 prescriptions for Risperidone and Seroquel were written in 2014 for children under 2 years old; 83,000 prescriptions for Prozac have been given to children under 2; 10,000 children age 2 or 3 have been given Adderall; the numbers for benzodiazepines are not given, but they are large.

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Federal Judge Allows Testimony on Seroquel/Tardive Dyskinesia Link

A Federal Judge ruled Monday that the science linking Seroquel to tardive dyskinesia is sufficiently reliable to be heard by a jury, saying that the theory had been tested, peer reviewed and sufficiently accepted by the medical community. The judge further noted that Seroquel’s FDA-approved label warns of tardive dyskinesia as a potential side effect, and that many reliable medical studies suggest that Seroquel and other antipsychotics can cause the condition.

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AstraZeneca, PTSD And A Buried Seroquel Study

by Pharmalot

File this under ‘hidden clinical trial disorder.’ For a decade, the US military regularly prescribed its service members atypical antipsychotics, which are approved to treat schizophrenia and bipolar disorder, for various off-label uses, notably insomnia and post-traumatic stress disorder. And the antipsychotic that was most widely prescribed has been the Seroquel pill, which is sold by AstraZeneca.

For instance, a 2009 review of off-label use in the Veterans Affairs health care system found that 60 percent of patients who received an antipsychotic had no record of a diagnosis for which these drugs are approved. The largest proportion of prescriptions for off-label use were written for PTSD and Seroquel had the greatest off-label use (see this).

Last year, the armed services issued more than 54,500 prescriptions for Seroquel alone, which was, by far, the most for any antipsychotic (see here). And by 2009, Seroquel became the VA’s second-biggest pharmaceutical expenditure, reaching $125.4 million, up from $14.4 million in 2001 (back story).

This off-label use occurred even though VA clinical guidelines issued in 2004 stated that “there is insufficient evidence to recommend atypical antipsychotics for the treatment of PTSD” (see page I-5 here). By 2010, though, the VA guidelines were recommending atypical antipsychotics for augmented therapy, reflecting various small studies that indicated the pills were useful in treating symptoms (see page 151).

By 2008, however, AstraZeneca (AZN) was aware of at least one study that indicated Seroquel – when added to an existing therapy – was no better than a placebo in reducing PTSD symptoms, and 65 percent of the participants experienced side effects related to the drug. But the study, which was sponsored by the drugmaker, was never published and a VA spokeswoman says the agency was not aware of its existence. At some point, however, the results were posted on the AstraZeneca web site (here it is).

The disclosure comes amid a growing controversy over hidden clinical trial data that has plagued the pharmaceutical industry. In recent years, scandals over undisclosed data linked to serious side effects involved Merck and its Vioxx painkiller, as well as the Avandia diabetes pill sold by GlaxoSmithKline. In fact, Glaxo recently pledged to make data available after paying a $3 billion fine, in part, for failing to release some Avandia data (read here).

The failure to disclose the Seroquel study prompts concern, experts say, not only because AstraZeneca failed to make the findings known, but because antipsychotics have been linked to irregular heartbeats. For instance, a 2009 study in The New England Journal of Medicine found the rate of sudden cardiac death doubled for those taking atypical antipsychotics, and there were three such deaths each year for every 1,000 patients taking such a drug (here is the abstract). The Seroquel study says that electrocardiagrams were taken, but there is no mention of any findings.

For these reasons, industry critics say the Seroquel study is only the latest example of a clinical trial result that should have been publicized, especially given what was growing use in the military for an unapproved purpose. “This seems to be important and useful information that should be publicly known,” says Yale University cardiologist Harlan Krumholz, who has pushed for greater disclosure (read this). “It speaks to the importance of the totality of data being available for public scrutiny.”

There was no explanation given by the drugmaker for not publicizing the study, but the failure to do so raises questions about the extent to which AstraZeneca has willingly shared all the available data about its drug and just how difficult it can be to identify and access some of this data. The only other place that any information about this study is available is on ClinicalTrials.gov, but the results are not noted (see here).

However, the Seroquel brand – there is Seroquel and Seroquel XR – has been a huge seller for AstraZeneca, which has been struggling to bolster its pipeline at the same time that various big-selling medicines have lost patent protection. Last year, the Seroquel brand accounted for 17 percent of total sales of $33.6 billion; the only drug to ring the register even more was the Crestor cholesterol pill.

As for the VA, the agency spokeswoman notes that last year, a study sponsored by the VA found that Johnson & Johnson’s Risperdal antipsychotic was not effective in reducing PTSD symptoms (read here). The agency acknowledged this “called earlier studies on this topic into question. Previous small, single-site studies were considered impressive because they involved veterans with chronic PTSD who were not responding” to antidepressants and suggested “augmentation with atypical antipsychotics,” according to a VA statement.

At least one of those small studies was co-authored by Mark Hamner, an associate professor of psychiatry at the Ralph Johnson VA Medical Center in Charleston, South Carolina (see here). A study published in 2003 in the Journal of Clinical Psychopharmacology (read this) concluded that Seroquel is “well tolerated and may have efficacy in reducing PTSD symptoms in patients who have not had an adequate response other medications.”

Hamner, who also co-authored a 2005 paper that found Seroquel improves sleep disturbances in combat veterans with PTSD, has been a paid speaker for – and a consultant to – AstraZeneca and has also received grant money from the drugmaker (look here). We asked him if he was aware of the study that had not been published, but he did not respond to the question and referred us to VA public affairs.

This was not the only instance, by the way, in which the handling of Seroquel data has been inconsistent. Two versions of another study, which explored the use of the pill for maintenance treatment of major depressive disorder, reveal an inconsistency concerning QT prolongation, the medical term for irregular heartbeat. One version was published in a journal two years ago and the other, which concluded in January 2008, is located on the AstraZeneca web site.

The published paper states “there were no clinically relevant mean changes from baseline in vital signs, ECG, hematology, or clinical chemistry parameters” (see page 970). But the same study from the web site reports clinically relevant changes in the QT interval in more than one place (see page 15). We reached out to Michael Leibowitz of the psychiatry department at Columbia University about the discrepancy, but he has not responded.

An AstraZeneca spokeswoman, meanwhile, wrote us that “the traditional presentation of clinical trial results is in the form of a group mean (average) change and this is reported in the clinical study report and the publication. The interpretation of ‘no clinically relevant mean changes’ is supported by the data. When secondary analyses, like the ECG shift analysis, do not contradict the mean changes (which are the primary analyses) they are generally not included in study publications.” Of course, ‘not generally’ does not mean never.

Seroquel- AstraZeneca settles with South Carolina

by goupstate.com

The S.C. Attorney General’s Office has secured a $26 million settlement against the multi-billion pharmaceutical company AstraZeneca for violating the state Unfair Trade Practices Act by willfully misleading consumers on the potentially serious side effects of the anti-psychotic drug Seroquel.

The settlement order was filed Aug. 22 and is the third award, and final case against anti-psychotic drug manufacturers in South Carolina, that the Attorney General’s Office has prosecuted since 2009. The cases began under former Attorney General Henry McMaster, who contracted with the Spartanburg law firm of Harrison, White, Smith and Coggins to prosecute the case on behalf of the state. The Spartanburg firm then contracted with two other firms in Columbia and Houston to assist with the litigation, which continued under Attorney General Alan Wilson.

In the lawsuit order, the company agreed to pay $26 million, which includes $20 million in damages and restitution to the state, $5 million in penalties and $1 million in trial costs. In 2010, AstraZeneca had $5.3 billion in worldwide sales including $3.75 billion in the U.S.

Bryan Stirling, deputy attorney general, said the settlement is fair to the state. A portion of the funds will go into the general fund, some will go to Medicaid and other funds to insurance companies.

Stirling said the Attorney General’s Office sued on behalf of the state and the state agencies that paid additional funds because of the medication side effects.

AstraZeneca did not admit any wrongdoing or violation, but agreed to pay the sum to resolve the state action, according to the order signed by Circuit Court Judge Roger Couch.

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„After years of costly litigation, we decided that settling this case was the appropriate way to resolve the matter and allow the company to focus on our core mission of delivering meaningful medicines to patients,“ according to a statement issued by Tony Jewell, AstraZeneca senior director of corporate communications.

The lawsuit maintains that AstraZeneca violated the state’s Unfair Trade Practices Act by willfully misleading consumers of Seroquel, a second generation anti-psychotic drug, on the risk of diabetes, high blood pressure, weight gain and other serious health risks. AstraZeneca was aware of the risks, but failed to include a warning for the potential for weight gain and diabetes in its warning label for many years, the lawsuit states.

After Seroquel was launched, the U.S. Food and Drug Administration sent letters to AstraZeneca in 1998 and 1999 warning of the „false and misleading campaign in its promotion of Seroquel,“ the lawsuit states.

The FDA noted the following false and misleading statements: claims that Seroquel is effective in mental conditions including bipolar disorder and schizoaffective disorder; AstraZeneca’s claims as to how Seroquel works and that the drug was safer and more effective than first generation anti-psychotics.

The FDA also cited the company for failing to disclose risks and important warnings including neuroleptic malignant syndrome, a life-threatening neurological disorder caused by an adverse reaction to neurological or anti-psychotic drugs; tardive dyskinesia, a disorder of involuntary, repetitive muscle movements; orthostatic hypotension, sudden low blood pressure; and seizures in its labeling.

The lawsuit alleges that even after the 1999 letter, the labeling was still misleading and the federal agency again admonished AstraZeneca in 2006 for false and misleading marketing.

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The lawsuit was based on Unfair Trade Practices Act violations that the Seroquel package insert through Jan. 26, 2009 was willfully, deceptively and misrepresented and/or concealed the drug’s dangerous side effects.

This case marks the third successful case prosecuted by state Attorney General’s Office against manufacturers of second-generation anti-psychotics. The first case against Eli Lilly settled for $45 million and Circuit Court Judge Roger Couch ordered a $327 million in damages last year following a jury verdict against Janssen Pharmaceuticals Inc., a subsidiary of Johnson & Johnson, for the anti-psychotic drug, Risperdal. Janssen has appealed that award.

The Risperdal award is believed to be the largest in the state’s history against a company found to have violated the state’s Unfair Trade Practices Act.

According to AstraZeneca, another similar case is pending in Mississippi involving Seroquel.

The company has settled similar cases in New Mexico, Utah and Montana this year.

Journal retracts antipsychotic study when all subjects’ PET scans turn out to be unreliable or invalid

by Retraction Watch

The Journal of Psychiatric Researchis retracting a 2010 paper claiming to show a relationship between quetiapine (Seroquel) and certain lab tests and brain scans, after it turns out the brain images were either unreliable or invalid.

Here’s the notice for “Relationship between dopamine D2 receptor occupancy, clinical response, and drug and monoamine metabolites levels in plasma and cerebrospinal fluid. A pilot study in patients suffering from first-episode schizophrenia treated with quetiapine”:

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).

This article has been retracted at the request of the Editors

Key results are based on invalid data, according to a recent notification by the authors. The findings of the article are significantly related to dopamine D2 receptor occupancy data, obtained from a Positron Emission Tomography (PET) scan in five individuals. According to new evidence, PET data of two out of these individuals did not show a reliable signal at all, while the PET results of the remaining three subjects are partly invalid. As a result, the reported findings are most likely incorrect. Journal of Psychiatric Research is dedicated to the highest scientific standards, therefore, this article has been retracted. The Editors regret if any misleading conclusions have been drawn from this publication, and apologies are offered to the readers of the journal.

The study was partially funded by Seroquel maker AstraZeneca, which paid more than half a billion dollars to the U.S. government last year to settle charges it paid “kickbacks to doctors as part of an illegal scheme to market [Seroquel] for unapproved uses.” It has been cited six times, according to Thomson Scientific’s Web of Knowledge.

It’s not clear how the problems with the data came to the attention of the authors. We tried contacting the editors of the journal, and the corresponding author, and will update with anything we hear back.