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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Chantix and depression on stopping smoking.

Yesterday I saw a couple of newspaper reports on the potential link between Chantix and psychiatric side effects, including discussion of some of the stories reported by people on this blog.
http://www.nj.com/starledger/stories/index.ssf?/base/news-13/1203831450252170.xml&coll=1

I’ve written before about risks for depression on stopping smoking and we have also talked about psychiatric symptoms occurring while using Chantix. Right now we really don’t know whether these symptoms of depression are directly caused by Chantix, by stopping smoking or by other things but have captured the headlines because over 5 million people have used Chantix in a short space of time. One thing that is clear is that serious psychiatric side effects are rare while using Chantix – probably somewhere between 1% and one per thousand. So it is important to keep the risks in perspective and to bare in mind that right now we are not absolutely sure that Chantix has caused these serious adverse events. Its also important to bare in mind that continued smoking has 50% chance of killing you, and a virtual certainty that it will cause you to suffer non-fatal illnesses that affect your life.

But I’ve been contacted by a number of people who reported that their mood was fine before they started taking Chantix and they became uncharacteristically short tempered and depressed while on it. One particular question that I’ve been asked is how long do these feelings last for? We’ve discussed before how the mood disturbance on stopping smoking typically peaks in the first week and has largely resolved by the fourth week in smokers quitting without taking any medication, but of course that’s the average and there can be big differences between individuals.

So I’d really appreciate it if readers who quit smoking for a period of time could write in and comment on what kind of effect it had on their mood, and the time course of any mood disturbance (i.e. how long after stopping smoking was it at its worst, and how long before it was OK again). Please comment on whether or not you used any medicine (including NRT) at the time and whether you thought the medicine helped or made the mood disturbance worse. I think it may be helpful for those who have experienced mood swings while quitting smoking to hear the experiences of others.

Labels: Chantix, depression, jonathan foulds, smoking cessation, withdrawal

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Can quitting smoking trigger depression?

Adolescent smokers are more likely than non-smokers to subsequently develop depression, and adult smokers are more likely to have either current depression or a history of depression than adult non-smokers. So although some have suggested that tobacco may have some component that “medicates” depression, the evidence for this is not at all clear. But for the smoker who has previously suffered a major depressive episode it is reasonable to wonder whether stopping smoking might increase the risk of suffering another episode of depression.

Depression is one of the most common and most unpleasant of all illnesses. It is characterized by feeling consistently sad, hopeless and pessimistic for more than 2 weeks (usually much longer), and often involves sleep disturbance, fatigue and changes in appetite. Perhaps most importantly, major depression is a risk factor for both attempted and completed suicide. So anyone who has ever suffered from major depression may understandably be very reluctant to do anything that may increase the risk of feeling that bad again. Remembering that low/depressed mood (which is not the same as full blown depression) is one of the symptoms of nicotine withdrawal, one can understand why someone with a history of depression would become concerned when they experience the onset of depressive symptoms after quitting smoking. Some studies find that people with a history of depression have a lower quit rate when they try to quit smoking, compared to those without such a history. One reason for this may be that onset of depressive symptoms raises the concern that a major depressive episode may return and triggers a return to smoking. However, a critical question is whether such fears are justified. Can quitting smoking increase the risks of onset of major depression?

Professor John Hughes, of the University of Vermont recently reviewed all the published studies providing evidence relevant to this question. The rate of major depression in the year after successfully quitting varied considerably across studies, from as low as 1% to as high as 31%. There was fairly consistent evidence that people with a history of major depression were more likely to have another episode after quitting, but this is not surprising as people with a prior history of depression are more likely to have another episode regardless of whether they quit smoking or not. Two studies by Professor Stan Glassman at Columbia University found that depression occurred more frequently in people with a history of depression who succeeded in quitting smoking compared with those who continued to smoke. In his review, Professor Hughes commented that none of the studies provided conclusive evidence and that there was a high risk of “publication bias”. This refers to the tendency for studies that don’t find a difference/effect to be less likely to be published. So what can we conclude from all this?

It looks likely that having a history of major depression is associated with slightly greater difficulty quitting smoking, and an increased risk of recurrence of depression in the months/years after quitting smoking. It remains uncertain whether quitting smoking can actually trigger an occurrence of depression, although it is clear that the majority (69-99%) of people who quit (even those with a history of depression) do NOT experience major depression within a year of quitting.
But how might this affect the choice of treatment, particularly for those with a history of depression? If I had a close relative who wanted to quit smoking but had a history of major depression, my advice would be as follows:
1. To ensure that you get the best advice and support, attend a treatment center with staff who have been trained to provide tobacco treatment, including access to medical staff with experience providing the range of tobacco treatment medications.
2. To increase the chances of successfully quitting AND preventing unpleasant withdrawal symptoms make sure you use an adequate dose of medication approved for smoking cessation. For the heavy smoker that should involve discussing with the doctor the potential advantages of combination therapy, such as Zyban (bupropion), plus the nicotine patch, plus one of the acute dosing nicotine replacement therapies (nicotine gum, lozenge, inhaler or nasal spray).
3. Make use of all the counseling support services available – ideally combining attendance at regular group or individual appointments, plus registering with a smoking cessation website (e.g. www.quitnet.com ), plus use of a telephone quitline.
4. Don’t start reducing the prescribed medication until you are feeling very confident about maintaining abstinence from tobacco and have discussed it with your prescriber. As a rule of thumb, don’t consider reducing your prescribed smoking cessation medications until you have had fourteen consecutive days with no cravings, withdrawal symptoms or near lapses.
5. Stay engaged in counseling for at least a few months (and ideally longer) after you have come off your smoking cessation medications. This could be as simple as scheduled monthly appointments or telephone calls, but even this relatively infrequent contact during months 4-12 after quitting smoking will help maintain focus on abstinence and will enable the counselors to monitor symptoms and treat as required.

Now all of this may sound like a great deal more work than people typically plan on when they try to quit smoking. It is. But I would remind my relative that this is a difficult but life-saving behavior change they are about to embark on. One likely to add ten healthy years to their life. Its well worth the effort both to successfully quit and to look after ones mental health in the process.

Labels: bupropion, cessation, depression, nicotine addiction cigarette smoking tobacco

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