Varenicline ( Chantix ) does not produce depression or suicide: new study

The smoking cessation medicine, varenicline, has proven safe and effective in numerous placebo-controlled trials, but in the post-marketing phase there were numerous reports of patients experiencing “neuropsychiatric effects” ranging from poor concentration all the way to suicide. In July 2009, the US Food and Drug Administration (FDA) required the manufacturers of both varenicline and bupropion to add new “boxed warnings” to the product labeling based on continued review of postmarketing adverse event reports. These issues have been discussed on this blog before and many readers have provided very useful comments based on their own experience (you can find these by typing “varenicline “ in the box on the right and clicking on “search health experts”).

Today a major new study of this issue was published in the British Medical Journal (BMJ) by Professor Gunnell and colleagues of the University of Bristol in England. One of the main strengths of this study was its size. The study used the UK General Practice Research Database (GPRD) which collects all the clinical data and prescribing information from 500 family doctors (GPs) throughout the UK (covering 3.6 million patients). They identified all adult patients who were prescribed a smoking cessation medication between September 2006 and May 2008 and then searched their records for occurrence of suicide, self-harm (non-fatal self injury), and being prescribed an antidepressant medication in the following 6 months. Overall 80,660 patients were included in the study (63,265 on NRT, 6422 on bupropion and 10,973 on varenicline). So this is by far the largest and most thorough study examining this issue.

The researchers recognized that smokers are at increased risk of suicide and that smoking cessation itself can cause mood disturbance, and so they decided to compare the rates of adverse events in patients using varenicline with patients using nicotine replacement therapy (NRT) or bupropion. This is an excellent way to assess the risks of varenicline as compared with comparable patients trying to quit smoking, particularly as there is no concern about NRT causing depression or suicide. Another strength of this study was that the researchers had access to the patients’ prior medical history and so were able to control for potential differences in the characteristics of the patients using the different treatments.
Overall there were 166 episodes of self harm, 37 episodes of suicidal thinking and 2 suicides during the follow-up period. Both the suicides were in patients who had used NRT (no suicides in the 10,973 patients using varenicline) and there was no statistically significant increased risk of suicide, self-harm, suicidal thoughts, or subsequent use of antidepressants in patients using varenicline or bupropion as compared with NRT. In fact patients prescribed varenicline appear to have a significantly REDUCED risk of needing a prescription for antidepressants during the subsequent months. 208 people died during the follow-up period and patients on varenicline were significantly LESS likely to have died than patients taking NRT (although this analysis only controlled for age and sex and the effect may diminish when a wider array or risk factors are controlled for).
Overall, this large study found only 18 episodes of self harm out of 10,973 smokers prescribed varenicline, a proportion not significantly different from NRT or bupropion. In addition it found that significantly fewer varenicline-treated patients had a subsequent need for antidepressants.

The well controlled placebo-controlled trials found no evidence of varenicline causing more suicidal thoughts than placebo, but patients with serious mental health or medical problems were largely excluded from those studies. This sample, however, was a real world patient sample,. 10% had a history of alcohol misuse, 5% were using antipsychotic medication, 13% anti-anxiety medication and 24% antidepressants. 11% had experienced a previous suicide related event. So when such a large, well-designed study like this finds really no evidence to support the claim that varenicline causes depression or suicide I am inclined to believe the evidence.
I should disclose here that I have done consulting work for manufacturers of all of these products, but none of the authors of this report receive any funding from any of these companies.

This paper provides considerable reassurance over concerns that varenicline causes suicide. The data shows that it does not.

The reference and link for the paper are:

Gunnell D, Irvine D, Wise L, Davies C, Martin RM. Varenicline and suicidal behavior: a cohort study based on data from the General Practice Research database. BMJ 209: 339 (in press)

http://www.bmj.com/cgi/content/short/339/oct01_1/b3805?rss=1

Labels: bupropion, champix, Chantix, depression, Gunnell, jonathan foulds, NRT, self-harm, suicide, varenicline

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