GSK’s May 2006 Analysis of Paxil Clinical Trials Confirms Risk in Adults
For its meta-analysis of suicidality data from the adult clinical trials, the FDA asked companies to submit data only from short term depression studies up to 17 weeks, which had at least 30 patients in the study. GSK decided to do its own blinded analysis of its adult clinical trial data. The results of the new analysis showed: “In adults with MDD (all ages), there is a statistically significant increase in the frequency of suicidal behavior in patients treated with paroxetine compared with placebo.” (http://www.baumhedlundlaw.com/23.pdf)
The masking of this risk in previous analyses was the result of a contamination of the data-set from inappropriately included anomalous studies. Once these studies were excluded due to FDA’s criteria, the increased risk of suicidality in adult patients taking Paxil, which had been evident from GSK’s initial submission, reappeared. The odds ratio is 6.7.
As a result of GSK’s recent analysis, GSK strengthened Paxil’s label to include this new information and sent a “Dear Doctor” letter to every doctor in the United States including this information. Id.
The Question of Efficacy
Doctors must weigh the benefits of drug treatment versus the risks. In order to do a proper risk benefit analysis, a doctor must be aware of the degree of effectiveness of the drug – not just drug company hype. Is the drug extremely effective or only marginally effective? Doctors know the drug was approved by the FDA, but do they know the FDA’s standards for approving a drug as effective?
In an analysis of efficacy data submitted to the FDA between 1987 and 1999 for six of the most popular selective serotonin reuptake inhibitor (SSRI) antidepressants, 75 to 80% of the response to medication was duplicated in placebo groups. (Kirsch and Moore, “The Emperor’s New Drugs: An Analysis of Antidepressant Medication Data Submitted to the U.S. Food and Drug Administration,” Prevention & Treatment, Volume 5, Article 23, July 15, 2002.) These data were the basis on which the medications were approved by the FDA. The researchers explained that the “small difference between the drug response and the placebo response has been a ‘dirty little secret’ known to researchers who conduct clinical trials, FDA reviewers, and a small group of critics who analyzed the published data …” Kirsch, Moore et al., “Antidepressants and Placebos: Secrets, Revelations, and Unanswered Questions,” Prevention & Treatment, Volume 5, Article 33, posted July 15, 2002 (http://www.baumhedlundlaw.com/24.pdf), Moncrieff and Kirsch, “Efficacy of antidepressants in adults” BMJ July 2005
FDA approval of these drugs implies that the data were strong enough and reliable enough to warrant approval, however, as one FDA memorandum written by Dr. Paul Leber illustrates, the FDA’s standards for approving antidepressants as effective are not robust: “Approval [of the antidepressant] may … come under attack by constituencies that do not believe the agency is as demanding as it ought to be in regard to its standards for establishing the efficacy of antidepressant drug products.” (http://www.baumhedlundlaw.com/26.pdf)
No Scientifically Reliable Evidence that Declining Suicide Rates are the Result of Increased Prescriptions of Antidepressants
On the issue of national suicide rates going down and, in particular, on the possible impact of antidepressants on these rates, as one renowned expert has noted: “This argument is like saying that, because there has been an increase in storks seen recently and a coincidental increase in births, babies are therefore brought by storks.” (Declaration of Dr. David Healy, Tucker v. GSK.)
In fact, according to Gunnel et al. 1, “Antidepressants and suicide: what is the balance of benefit and harm,” British Medical Journal (BMJ), 2004; 329:34-38 (3 July):
Surprisingly, direct evidence that antidepressants prevent suicide is hard to find. … In the most comprehensive synthesis of data from randomised trials, Khan and colleagues found no evidence of a beneficial effect of antidepressants on suicide.
Gunnell, citing Khan A, Khan S, Kolts R, Brown WA. “Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports,” Am J Psychiatry 2003;160: 790-2
The authors also pointed out that “Suicide is rare, even among people with depression. [Cite omitted.] Thus, most clinical trials have insufficient power to provide clear evidence on the effect of antidepressants on suicide.” Gunnell citing Jick SS, Dean AD, Jick H. Antidepressants and suicide. BMJ 1995;310: 215-8.
According to a study by Herman Van Praag published recently in World Journal of Biological Psychiatry titled “A Stubborn Behaviour: the Failure of Antidepressants to Reduce Suicide Rates,” despite the increased use of antidepressants “completed suicide has remained quite stable” and “suicide attempts even seem to have increased.”
For over a decade and a half, SSRI manufacturers have enjoyed enormous financial benefits from the flawed results of their defective analyses and their manipulations of the clinical trial data. They have been further shielded by their own failure to legitimately study and examine this serious risk. Instead, they have relied on studies that were not designed to detect a risk and conducted illegitimate analyses from them. Like an ostrich, they stuck their heads in the sand and pretended that no such risk could possibly exist, so why look? They have blamed patients, arguing that it’s “the disease, not the drug.” The FDA, likewise, has been derelict in its duties in protecting the public health on this issue. While it appears that the FDA has finally taken the issue more seriously, it is 20 years and thousands of lives too late. Through [our] representation of the more than 100 families who have lost loved ones to suicide or who have attempted suicide themselves while under the influence of an antidepressant, [we are] touched by a tremendous sense of duty to prevent this terrible tragedy from continuing to happen to others. [We are] motivated by our clients to seek out and expose the truth so their loved ones’ deaths will not be in vain.
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1. David Gunnell is professor of epidemiology, University of Bristol and Deborah Ashby is professor of medical statistics, Queen Mary’s School of Medicine and Dentistry.