by Gibbons RD, and Mann JJ.American Journal of Psychiatry. 2013 170[12]:1460-1467.
OBJECTIVE In 2009, the U.S. Food and Drug Administration issued a black box warning for varenicline regarding neuropsychiatric events. The authors used data from randomized controlled trials and from a large Department of Defense [DOD] observational study to assess the efficacy and safety of varenicline.METHOD The authors reanalyzed data from the 17 placebo-controlled randomized controlled trials [N=8,027] of varenicline conducted by Pfizer, using complete intent-to-treat person-level longitudinal data to assess smoking abstinence and reports of suicidal thoughts and behavior, depression, aggression/agitation, and nausea and to compare effects in patients with [N=1,004] and without [N=7,023] psychiatric disorders. The authors also analyzed a large DOD data set to compare acute [30-day and 60-day] rates of neuropsychiatric adverse events in patients receiving varenicline or nicotine replacement therapy [N=35,800] and to assess reports of anxiety, mood, and psychotic symptoms and disorders, other mental disorders, and suicide attempt.RESULTS In the randomized controlled trials, varenicline increased the risk of nausea [odds ratio=3.69, 95% CI=3.03-4.48] but not rates of suicidal events, depression, or aggression/agitation. It significantly increased the abstinence rate, by 124% compared with placebo and 22% compared with bupropion. Having a current or past psychiatric illness increased the risk of neuropsychiatric events equally in treated and placebo patients. In the DOD study, after propensity score matching, the overall rate of neuropsychiatric disorders was significantly lower for varenicline than for nicotine replacement therapy [2.28% compared with 3.16%].CONCLUSIONS This analysis revealed no evidence that varenicline is associated with adverse neuropsychiatric events. The evidence supports the superior efficacy of varenicline relative to both placebo and bupropion, indicating considerable benefit without evidence of risk of serious neuropsychiatric adverse events, in individuals with and without a recent history of a psychiatric disorder.
by A. Eden EvinsAmerican Journal of Psychiatry. 2013 170:1385-1387.
… Varenicline doubles to triples the likelihood of quitting smoking over placebo, and its most common side effects are nausea and vivid dreams. With the Gibbons and Mann report joining other published studies finding no increased incidence of psychiatric adverse events with varenicline over placebo or active controls, it is time to unring the alarm bell on varenicline and use this effective medication on a larger scale.
Pharmalotby Ed Silverman09/18/2013Faced with declining sales of its controversial Chantix quit-smoking pill, Pfizer has undertaken various educational and promotional efforts to revive its fortunes. And as part of the plan, the drugmaker funded a study that found people with a history of depression were no more likely to become depressed or have suicidal thoughts than those given a placebo. The study was designed to determine whether Chantix would help people who had been treated for depression quit smoking without worsening their depression and those findings were positive. Among those on Chantix, 35 percent did not smoke, compared with 15 percent of those in the placebo group. About three-quarters of the 525 participants regularly took antidepressants or anti-anxiety drugs.
However, the study also found that, during the final 30 days of a three-month treatment phase, 15 people taking Chantix experienced suicidal thoughts, compared with 19 on a placebo and another person who exhibited suicidal behavior. At the outset, 88 people taking Chantix reported any lifetime history of suicidal ideation or behavior, compared with 89 of those on placebo [here is the study]. The findings, which were published in The Annals of Internal Medicine, could be used to mitigate long-standing concerns about the extent to which Chantix causes psychiatric side effects, an issue that prompted Pfizer to add warnings that its pill is connected to suicidal thoughts and behavior after a spate of negative publicity [see this]…
More recently, Pfizer took charges totaling nearly $300 million to settle hundreds of product-liability lawsuits that were filed in the US, although the drugmaker continues to face litigation in Canada. Meanwhile, Chantix sales are slumping – revenue was $755 million in 2010 and fell 11 percent by last year to $670 million. Through the first six months of this year, sales were down 5 percent…
But lead author Robert Anthenelli, a psychiatry professor at the University of California San Diego School of Medicine, offers a caveat. “Because depression is an episodic illness prone to recurrence and, since a minority of smokers with past histories of depression may be at increased risk after quitting, it’s important for clinicians to remain vigilant and monitor their patients closely,” he tells Reuters.
We should note that in addition to funding the study, Pfizer also funded the editorial support and five of the seven authors are Pfizer employees. Anthenelli received funding from the Department of Veterans Affairs for writing the manuscript and has worked as a consultant to Pfizer and received about $400,000 for fees, meals, travel and research between 2009 and 2012 [look here]. Another author, Chad Morris of the University of Colorado, received about $500,000 in research grants from Pfizer over the last three years [see this]. However, the link to the disclosure form provided with the study does not list any details for any authors.
[UPDATE: We contacted the Annals of Internal Medicine to ask why the disclosure information had not been provided and Christine Laine, the editor, wrote us this: "The problem was a typo in the URL link to the forms. The disclosures are all accessible presently and the authors… did disclose potential conflicts of interest. Thanks for bringing this to our attention." And so, here is the correct link to the disclosures.]
Or we could just unring the bell on Gibbons and his friends – as here
http://hcrenewal.blogspot.com/2013/11/when-is-disclosure-not-disclosure.html
Since anything can be called “depression,” anyone in any study can have a “prior history of depression,” thereby negating all adverse psychological effects of psychiatric drugs as due to a pre-existing condition — if you cared to argue that way.
I think I long for the time when experiments on human beings with a toxic poison for profit becomes a thing of the past. Unfortunately I think that past failures become just an excuse for a lucrative future enterprise. Such is life. Oh well….