Doctors Under the Influence? The Real Story

About a month ago, my colleague, Dr Michael Steinberg, and I were contacted by a journalist for BusinessWeek magazine, who said she was interested in discussing “smoking cessation” with us, focusing on a paper we had recently published in Annals of Internal Medicine, entitled, “The case for treating tobacco dependence as a chronic disease.” On talking to Ms Weintraub, however, the focus of her questions very swiftly shifted to the topic of whether we have ever done any paid work for pharmaceutical companies and whether that presented a conflict of interest. Of course we explained that we have done some consulting work and presentations for pharmaceutical companies who make smoking cessation products, and we pointed out that this, including the names of the companies, was clearly disclosed at the end of our published paper, as is common practice when publishing in medical journals.

The journalist, recognizing that it is our practice to disclose our funding wherever it comes from, in our publications and presentations, then asked if we do so to our patients. We thought about this a little and stated that we don’t, and that this isn’t normal practice in any area of healthcare. I commented that when I go to see my own doctor about my asthma, I expect her to assess and treat my asthma to the best of her ability, and if she started telling me that she has been paid to do some work for pharma companies, I’d be a bit puzzled as to why she was telling me this. I am neither surprised nor concerned to hear that my doctor might do some work for pharma companies. It is probably a sign that she is regarded as having expertise in that field. Personally I don’t feel this is information I need to be provided with on a routine basis, and that if one day I decided I had a reason to ask, I’d do so and expect to be told. In fact I’ve never asked a medical doctor that question, nor ever thought of it. Similarly I don’t recall being asked by a patient, which is perhaps not surprising given that I’m a psychologist and don’t prescribe medicines at all.

I was then surprised when the journalist’s questions shifted from our article in Annals of Internal Medicine, to the new smoking cessation medicine, Chantix, which was barely mentioned (once) in the article. The questions were all about work we’d done for the manufacturer (Pfizer), and whether that made us biased towards the drug. The journalist appeared to be under the impression that the article aimed to persuade doctors to prescribe Chantix to patients for life. We explained that the article wasn’t about Chantix at all (the patient described in it wasn’t treated with Chantix) and that we do not recommend treating patients with any tobacco treatment medicines for life. We explained that we advise patients to use the medicines for as long as it takes to successfully quit smoking (typically until they have 14 consecutive days without cravings), and that the biggest problem we find is that patients often only use the medicines for a few weeks and go back to smoking. However, despite our repeated clarifications, we had a feeling that she was not particularly interested in the facts, but had an angle she wanted to pursue and was going to do it regardless.

So her article appeared in the June 26 issue of BusinessWeek under the title, “Doctors Under the Influence?” opposite a full-page cartoon depicting a doctor in a white coat being fed cash into his mouth, while simultaneously popping pills into the mouth of an open-mouthed patient. Get the idea? So I’d like to take this opportunity to clarify some facts and some issues that were badly misrepresented in the article.

Misrepresentation 1: In the opening paragraph, the article states that in our Annals of Internal Medicine publication we advised that addicted smokers should take prescription drugs for years to curb their cravings. In fact, nowhere in the paper did we advise that patients should take medicines for years. Rather, we state that some smokers may require extended treatment (both behavioral and pharmacological) to quit smoking. This is entirely consistent with the current US Public Health Service Clinical Practice Guideline, which states:

“For some patients it may be appropriate to continue medication treatment for periods longer than is usually recommended.

Although weaning should be encouraged for all patients using medications, continued use of such medications is clearly preferable to a return to smoking with respect to health consequences.” (p126).

Incidentally, the first of the 10 key recommendations of the US Public Health Service Clinical Practice Guideline states, “Tobacco dependence is a chronic disease that often requires repeated intervention….”.

Misrepresentation 2. The third paragraph points out that the paper was published around the time Pfizer was strengthening warnings on the labeling on its new smoking cessation drug, Chantix, and stated “This timing has fuelled concern that company-paid experts are trying to protect the drug…” In fact the paper described a case report of a patient who was successfully treated with other smoking-cessation medicines (not Chantix) over two years before Chantix was launched, and mentions the drug by its generic name (varenicline) only once in citing a paper showing that it was safe and effective for up to a year. In truth the paper is not about Chantix at all.

Misrepresentation 3. The title, attached artwork and overall thrust of the article implies that if a health professional has done some work for a pharmaceutical company, they must therefore be being paid by the company to get patients to use the drug. Well let’s think about that for a second. Healthcare providers who gain expertise in treating a specific health problem via their clinical work and research, whether it be tobacco addiction or diabetes, are clearly more likely to be offered paid work (including research funds) for their expertise by a range of interested parties, whether it be government organizations, non-profits, or pharma companies. None of these organizations are allowed to pay anyone to prescribe a specific medicine, and in my case, as a psychologist I don’t prescribe any medicines anyway. My consulting work has involved things like advising on clinical trial design, reviewing applications for research funds, discussing common barriers to quitting smoking, and advising on future potentially effective smoking cessation medicines. I have also provided presentations to doctors about smoking cessation medicines, so that they can become more knowledgeable both about these medicines and about effectively helping smokers to quit. None of these activities are linked to the medicines selected by patients at our clinic. As we very clearly explained to the journalist, our style at the Tobacco Dependence Clinic is to offer individual and group counseling and to show patients all the FDA-approved medicines for smoking cessation, and let them choose the ones they would like to try, based on a discussion of their pros and cons and of their own history. Only a minority of our patients choose Chantix.

Misrepresentation 4. The article implies that we have some kind of problem with disclosing our consulting work with pharma companies. On the contrary, our consulting work is stated very clearly on the specific paper that captured the journalist’s interest. In addition, both Dr Steinberg and I stated that we have no problem disclosing this work to patients if they ask, but we don’t see it as something that patients will want to have provided to them routinely. So we ask readers to consider whether they really want their hospital doctors to have a discussion with them about their various sources of income every time they see them. In considering this question, bear in mind that the more senior and the more “expert” the doctor you see, the greater the likelihood that they will have done work funded by a potentially long list of organizations. If the answer is yes, we will be happy to oblige, but until we hear that request consistently, we are happy to provide the information to patients on request.

Of all the misrepresentations in the article, the one that bothers me most is the entirely inaccurate picture the article paints of my colleague, Dr Michael Steinberg. He is without doubt one of the best medical doctors I have had the privilege to meet or work with. He has chosen to forego far more lucrative career options to focus on working as an academic hospital doctor and internal medicine specialist, with a specific clinical and research focus on helping the most addicted smokers to successfully quit. He has become a national expert on pharmacotherapy for smokers and so it is no surprise that many groups (including pharma companies) seek his expertise. He has every right to be paid for the work he does in sharing that expertise. I have no doubt at all that his clinical work is guided by the best scientific evidence, combined with his own expert judgment of what might be most helpful for the patient and an excellent clinical style that respects patient choice. The development of our Tobacco Dependence Clinic into one of the best clinical services for addicted smokers in the country is largely due to his expertise. Note that the service is funded by the New Jersey State Department of Health and Senior services.

As for myself, I continue to be happy for people to be fully informed about my funding, and to judge my actions and opinions on whether or not they are based on the best scientific evidence. Even the more positive things said about me in the article are inaccurate. I’m not a “celebrity in antismoking circles” and I never “launched an extensive telephone hotline for smokers” (I worked briefly as Director of Research for the UK charity, “Quit” which ran the UK Quitline for many years prior to my involvement). I find it an interesting coincidence that the BusinessWeek article, which appears to attempt to discredit reputations, is published less than a month before I am due to provide testimony as an expert witness in four law suits against tobacco companies. These lawsuits stemmed from the Florida-based “Engle” class-action lawsuit which led to the largest financial judgment of its type, ever ($145 billion against the tobacco industry). The class action was later decertified, resulting in these and numerous other individual cases, which the tobacco industry is obviously very eager not to lose. I’m sure this is just a coincidence, and that a magazine like BusinessWeek wouldn’t dream of being under the influence of big business itself.

FYI here are a couple of tobacco industry-friendly articles on the BusinessWeek website:

http://www.businessweek.com/investor/content/jan2008/pi20080129_262388.htm

http://www.businessweek.com/bwdaily/dnflash/content/jan2008/db20080129_130365.htm

So as far as BusinessWeek is concerned…...
doctors who have ever done work for a pharma company, then providing the most effective treatment to help smokers quit – unethical,
but multinational tobacco companies winning litigation and selling more cigarettes around the world – priceless.

You can find our original article in Annals of Internal Medicine at:
http://www.ncbi.nlm.nih.gov/pubmed/18378950?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

The citation is:
Steinberg MB, Schmelzer AC, Richardson D, Foulds J. Treating tobacco dependence as a chronic disease: a case illustration. Annals of Internal Medicine 2008 Apr 1;148(7):554-6.

Labels: BusinessWeek, Chantix, Chronic Disease, jonathan foulds, Pharmaceutical

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Chantix safety at the US Veterans Affairs Health Service

The US Department of Veterans Affairs (which provides healthcare for people who have served in the US armed forces) yesterday issues a bulletin on safety issues with varenicline. In addition to covering some of the safety issues that have been discussed previously on this blog, it provided some data on adverse events within the VA.

The report stated that between September 2006 and April 30, 2008 there were a total of 147,718 prescriptions for varenicline (69,765 unique patients) within the VA. As of May 26 2008 , VA healthcare providers had submitted 417 reports on possible adverse events associated with varenicline. The most common type of adverse event was vomiting (95), followed by nightmares/abnormal dreams (82), depression (68), agitation (33), suicidal ideation (31) and hallucinations (25). Other adverse events were reported much less frequently.

So the overall rate of adverse event reports appears to be around 6 per thousand, of which almost half consist of vomiting, abnormal dreams and other non-life threatening symptoms that are recognized as rarely occurring side effects of the drug. Interpretation of the rates of the other (primarily psychological) symptoms needs to bare in mind that the VA healthcare system provides fairly comprehensive and accessible mental health services and the rates of mental health problems in VA patients is therefore known to be higher than in the general population. For example, one recent study found that 40% of male VA patients were suffering from a current mental health disorder.
http://ajp.psychiatryonline.org/cgi/content/full/156/12/1924

With this background, and an annual rate of suicide attempts of 1% among adult smokers, the numbers of patient being reported as suffering these adverse events in the VA system does not appear to be particularly high. One patient was known to have committed suicide in association with varenicline use, and although every case of suicide is tragic, one case in almost 70,000 patients in the VA system is almost certainly less than the background rate of suicide in the VA system among patients not using Chantix. I am not saying that Chantix may prevent these symptoms or behaviors. However, even after allowing for under-reporting of adverse events (which is normal), the frequency with which these events are being reported among Chantix users does not appear to be above the frequency that we would expect these types of events to be occurring in patients not using Chantix (in fact its much lower). What this means to me is that there is nothing in this new data that stands out as a clear signal that Chantix likely caused these events (other than perhaps vomiting and abnormal dreams, which are known to be increased by Chantix).

Of course it is very difficult to interpret adverse event reports, which are not necessarily recorded in a very systematic manner. The data we have so far suggest the following:

1. Prescribers should continue to use varenicline as one of the first-line medicines shown to help treat nicotine dependence.
2. Prescribers should make patients aware of the potential side effects, including the relatively frequent effects that have been shown to be caused by the drug (e.g. mild nausea in around 30% of patients), as well as the much less frequent symptoms that have not been proven to be caused by the drug (e.g. depression).
3. Providers should follow the US Public Health Service Guideline that recommends not only assisting smokers to quit by prescribing an effective medicine, but also arranging follow-up with patients to monitor progress and side-effects etc. Patients should also be told to notify their doctor immediately if they experience any serious side-effects between appointments.
4. Patients should continue to consider varenicline as a safe and effective treatment for nicotine dependence, but should be prepared to keep in contact with their healthcare provider and to report onset of unpleasant/serious symptoms to that provider if they occur.
5. Additional placebo-controlled trials in more typical patient samples should be carried out, to provide further high-quality data on efficacy and safety.

Labels: champix, Chantix, cigarette smoking, jonathan foulds, safety, varenicline

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Chantix (varenicline) Safety

Last week a report was released by an organization called the “Institute for Safe Medication Practices” (ISMP) which claimed to have safety concerns about Chantix (varenicline, also marketed as Champix outside the United States). The Executive Summary of the report made two main recommendations:

1. Chantix should be avoided or used with caution by persons operating aircraft, motor vehicles or other machines (e.g. power stations) where a lapse in alertness or motor control could have serious consequences.
2. Patients and doctors should excercise caution in the use of Chantix (generally) and “consider the use of alternative approaches to smoking cessation.”

Given that most of us drive a vehicle, the report is basically suggesting that varenicline is such an unsafe drug that it should be avoided. These are strong recommendations, and have immediately resulted in the Federal Aviation Authority (FAA) and Federal Motor Carrier Safety Administration (FMCSA) adding varenicline to their list of drugs that should not be used by pilots or truck drivers. The report itself has not been published in a peer-reviewed journal and so it is reasonable to assess the quality of the data on which it was based, and to evaluate whether the recommendations are warranted on the basis of that data.

The ISMP report was based on an analysis of the frequency and type of serious adverse events that have been reported to the US Food and Drug Administration (FDA) about Chantix, in comparison to other drugs. In particular, the report noted that by the 4th quarter of 2007 Chantix “accounted for more reports of serious adverse events in the United States than any other drug.” This amounted to 988 reports about Chantix in the 4th quarter, as compared with 372 (Oxycodone) to 640 (Interferon Beta) reports about the next 5 most reported drugs.

The report then selected a sample (3063) of the total reports (excluding foreign or unclear reports) for slightly more detailed analysis. It noted that a much larger proportion of the reports about Chantix came from consumers (57%) than is typical of other drugs (26%) for which health professionals are the predominant source. The report also noted that a lower proportion of the reports about Chantix (2.5%) reported deaths, as compared with 17% of reports about other drugs.

The report summarized the most frequent medical terms included in the reports about Chantix. By far the most common term used was nausea (593), which was more than twice as common as any other reported symptom. It was also noteable that among the most commonly reported medical symptoms mentioned in the adverse event reports, many are also recognized nicotine withdrawal symptoms (i.e symptoms known to increase when smokers quit smoking, particularly without any treatment medication), such as depression (287), insomnia (242), anxiety (217), and weight increase (141).

Problems with the ISMP report and its conclusions

There are a number of fundamental problems with the quality of the data, analysis and interpretation in the ISMP report. Before discussing some of these, it is worth discussing the way that reports of serious adverse events are delivered to the FDA. There are 4 main sources of reports.

1. Members of the public can send reports directly to FDA, either by mail or via an on-line reporting system (and I have provided the link on previous posts on this blog about Chantix to ensure that reports reach FDA).
2. Health professionals can report adverse events to FDA.
3. Lawyers sometimes report adverse events to FDA.
4. The manufacturer is required to report to FDA any reports that are brought to its attention directly. Those adverse events that are already mentioned on the product labeling are reported on a quarterly basis, and novel symptoms must be reported within 15 days (expedited).

Reports from the first 3 of these sources are entirely voluntary and are made in a rather haphazard way. The ISMP report estimated that typically between 1 and 10% of serious adverse events are actually reported to FDA. It is commonly found that AE reports peak around two years after the launch of a drug, even if the drug becomes used more often thereafter. The purpose of the FDA’s reporting and monitoring system is to facilitate post-marketing surveillance and enable detection of patterns of adverse events that could potentially be caused by a medicine but were not detected in the initial placebo-controlled trials leading to drug approval. The main point here is that these reports are not made in a systematic way, and the frequency of reports can be influenced by factors such as (a) the frequency of use of the drug (b) the novelty of the drug (c) media coverage of the drug and (d) efforts by the company to interact with users in a manner that will lead to them hearing of and therefore being required to report on AEs.

With these factors in mind, here are some of the problems with the ISMP report:

1. The report fails to consider the frequency of the use of the drug when considering the number of adverse events being reported. Since its launch in August 2006 (i.e. less than 2 years), Chantix has been used by an estimated 5.5 million smokers in the United States. In 2007 alone it was used by 3.8 million new patients in the U.S. (6.2 million prescriptions). This is many times more than the other drugs listed in the ISMP report. For example, Etanercept (Enbrel, the drug with the 3rd largest number of adverse event reports to FDA) was launched in 1998, and has been used by a total of 450,000 patients WORLDWIDE in those 10 years. Comparing frequency of adverse events without adjusting for the frequency of drug use is so obviously inappropriate as to cast doubt on the reliability of the report as a whole.
As mentioned briefly in the ISMP report, many factors can affect the frequency of reporting of adverse events to FDA. In the case of Chantix, the widely publicized death of a rock musician (who was tragically shot by a neighbor in Texas) which his partner felt could have been related to Chantix, sparked off widespread media speculation about potential side effects. The manufacturer also offers a number of direct to consumer quit smoking services, including a free telephone hotline called “Get Quit”. Because this hotline is run by the manufacturer, whenever a caller mentions a symptom, they are immediately transferred to the medical department, the details are noted and the information reported to FDA. These events and procedures can have a large effect of increasing the number of serious adverse events reported and this was not adequately considered in the ISMP report. It is noteworthy that 92% of the events analyzed in the ISMP report came via the manufacturer.

2. The report fails to adequately consider the possibility that some of the reported adverse events may have been caused by nicotine withdrawal. The vast majority of those using Chantix were attempting to quit smoking, which itself is known to cause a range of nicotine withdrawal symptoms, including many of the symptoms most commonly reported to FDA and mentioned in the ISMP report (depression, insomnia, anxiety, weight increase). It is entirely plausible that many of these reported symptoms were caused by nicotine withdrawal rather than Chantix. In fact in the placebo-controlled trials of Chantix, withdrawal symptoms were REDUCED in those using Chantix.

3. The report doesn't adequately consider the serious health effects of tobacco dependence. The ISMP report characterizes the other comparison drugs as being “intended for serious illness in patients and have benefits that are accompanied by substantial risks. In comparison, varenicline is intended for use in healthy people to help stop smoking.” Unfortunately this statement indicates a misunderstanding of the nature of tobacco dependence as a serious illness causing the premature death of 50% of continuing smokers, and of the fact that a high proportion of patients using smoking cessation medications are already suffering from or at very high risk for smoking-caused illnesses, including some mentioned as adverse events in the report (e.g. cardiac arrhythmias).

4. The report inaccuratley characterizes the relative efficacy of varenicline versus other treatments. The ISMP report states that Chantix has similar long term quit rates to nicotine gum. This statement contradicts the findings of the new US Public Health Service Clinical Practice Guideline on Treating Tobacco Use and Dependence, which found a mean quit rate of 13.8% with placebo, 19% with nicotine gum and 33.2% with varenicline (p109) and that quit rates with varenicline are significantly greater than with the nicotine patch (p121). This Guideline, written after the recent labeling changes for varenicline, concluded that, “Varenicline is an effective smoking cessation treatment that patients should be encouraged to use.” (p113).

Probably the most basic problem with the ISMP report is its failure to consider the frequency of use of the medicines as a factor influencing the interpretation of the frequency of adverse events reported. It therefore remains unclear whether any of these serious adverse events were caused by varenicline. When added to the other problems of interpretation mentioned above, I prefer to rely on the recommendation of the US Clinical Practice Guideline, which resulted from a very thorough review of the available scientific evidence.

So what does this mean for patients considering quitting smoking? As always, rely on the advice of your own doctor rather than on reports in the media or the internet (including this one!).

The complete ISMP report can be found at:
Strong Safety Signal Seen for New Varenicline Risks
http://www.ismp.org/docs/vareniclineStudy.asp

Previous posts on this blog that are relevant to this issue are:
What is nicotine withdrawal syndrome? 3/6/07http://www.healthline.com/blogs/smoking_cessation/2007/03/what-is-nicotine-withdrawal-syndrome.html
Ten tips for coping with nicotine withdrawal. 3/7/07http://www.healthline.com/blogs/smoking_cessation/2007/03/ten-tips-on-coping-with-tobacco.html
Chantix: how does this new stop smoking medicine work? 4/15/07http://www.healthline.com/blogs/smoking_cessation/2007/04/chantix-how-does-this-new-quit-smoking.html
Can quitting smoking trigger depression? 6/16/07http://www.healthline.com/blogs/smoking_cessation/2007/06/can-quitting-smoking-trigger-depression.html
Chantix and mental illness. 08/12/07http://www.healthline.com/blogs/smoking_cessation/2007/08/chantix-and-mental-illness.html
Two new studies of Chantix (varenicline). 08/19/07http://www.healthline.com/blogs/smoking_cessation/2007/08/two-new-studies-of-chantix-varenicline.html
Does Chantix cause mental health problems? 9/20/07http://www.healthline.com/blogs/smoking_cessation/2007/09/does-chantix-cause-mental-health.html
Chantix (varenicline) safety being reviewed by FDA. 11/21/07http://www.healthline.com/blogs/smoking_cessation/2007/11/chantix-varenicline-safety-being.html
New study of Chantix in comparison with NRT. 11/28/07http://www.healthline.com/blogs/smoking_cessation/2007/11/new-study-of-chantix-in-comparison-with.html
Smoking and suicide. 4/22/08 http://www.healthline.com/blogs/smoking_cessation/2008/04/smoking-and-suicide.html

Full reports on the largest placebo-controlled trials of varenicline can be found via:
http://jama.ama-assn.org/cgi/content/full/296/1/47

Labels: cessation, champix, Chantix, cigarette smoking, jonathan foulds, Nicotine Replacement, safety, varenicline

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Smoking and suicide

It has long been known that people who smoke are at greater risk of attempting and committing suicide than people who don’t smoke. On the face of it this doesn’t seem particularly surprising as people who sometimes think that they would rather not live would appear to have less reason to quit smoking to improve their health and live longer.

But the recent concern about onset of depression and suicidal thoughts among people quitting smoking (who presumably are in a frame of mind in which they want to live longer when they decide to quit) has led to renewed interest in the relationship between smoking and suicide. A recently published study by Professor Ronald Kessler (Harvard University) and colleagues provided some data and analysis relevant to this issue.

The study involved a survey of a representative sample of the adult American English-speaking population (n=5692). The study found that 2.6% had seriously thought about committing suicide in the previous year, 0.7% had made a plan of how they would do it, and 0.5% had made an attempt. This study, like many prior studies, found that smokers were about two or three times as likely to have thought about or attempted suicide in the past year than non-smokers. Heavy smokers were generally more likely to have thought about suicide than light smokers.

This survey also included a diagnostic interview for recent mental disorders. Like other studies, it found that people with virtually any mental disorder (from specific phobias to bipolar disorder) were more likely to be smokers, with the strongest relationship being for substance use (people with dependence on other substances being around 5 times more likely to be smokers than those not having a substance use disorder). People with a mental disorder were also more likely to have suicidal thoughts or attempts.

The study then examined whether smokers remained at greater risk of suicidal thoughts or attempts, after controlling for mental disorders. Controlling for mental disorders reduced the association between smoking and suicidal behavior to the point that it was no longer statistically significant.

My own interpretation of the data from this and other studies, is that mental disorders or some other factors of which mental disorders are highly correlated (e.g. mental health or general satisfaction with ones life) are a risk factor for both smoking and suicidal behavior. Thus people who as kids are unhappy and have difficulties dealing with their emotion are more likely to take up smoking, and more likely to become addicted to tobacco, and as adults are less able to quit smoking and are also, by virtue of their dissatisfaction with life, more likely to consider and attempt suicide.

Thus the relationship between smoking and suicidality is very unlikely to be causal. It is also worth noting that the size of the association is not very large. About one in 200 non-smokers attempt suicide each year and about one in 100 smokers attempt suicide each year.

None of this provides a direct explanation or helps us understand what may be going on when an individual attempts suicide in close proximity to a time when they had been trying to quit smoking (with or without using Chantix). But it does give us some idea of the frequency of certain events in the population. Around 45 million Americans smoke. At least 15 million of them make a quit attempt each year, and at least 5 million have already tried Chantix. This would imply that in the past year around 450,000 smokers made a suicide attempt, and possibly as many as 150,000 of them in the same year they made a quit attempt. Assuming around 2 million Chantix users in one year, and the same rate of suicide attempts per year as other smokers, this would lead us to expect around 20,000 smokers to make a suicide attempt in the same year they used Chantix, even if a quit attempt or Chantix use had no effect on risk for a suicide attempt. The precise number of events expected by chance will of course vary a bit according to the study one bases ones estimates on. But either way, one would expect a large number of cases by chance.

Now none of this means that making a quit attempt, or taking any particular medication, could or could not affect an individual’s risk for depression or suicide. That is a more complex question. But it does demonstrate that we might expect to hear of a large number of cases of suicide attempts by smokers taking any commonly used medicine, even if that medicine had no causal relationship with the suicide attempt.

The full text of the study by Kessler and colleagues can by accessed via the following link:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17502801

Labels: Chantix, cigarette smoking, jonathan foulds, suicide

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Why Chantix may reduce alcohol consumption.

Some of those people who have posted comments on my blog have commented that when they were using Chantix (varenicline) their interest in drinking alcohol or smoking marijuana also decreased. There are a couple of obvious potential mechanisms for that effect. Firstly, we are all familiar with the association between smoking tobacco and other substance use. Smokers are much more likely to take other substances than non-smokers, and when a smoker has a drink it often increases their desire to smoke and vice versa. So Chantix may reduce other substance use simply by helping take out cigarettes as a trigger. In addition, there have been reports that in a small but significant proportion of cases, Chantix use has coincided with a period of low mood or depression. So it is plausible that those affected in this way may lose part of their taste or enthusiasm for a number of activities they had previously enjoyed (including alcohol).

But there is also some evidence from studies of experimental rats, which suggests that varenicline (Chantix) may have a more direct effect on alcohol consumption. Last year, Dr Pia Steenland and colleagues at University of California published a paper in the prestigious journal, “Proceedings of the National Academy of Sciences” Their study found that animals who became used to drinking ethanol (alcohol) and were then treated with varenicline showed reduced alcohol-seeking behavior, and reduced alcohol consumption, without having any effects on water or sugar consumption. The authors concluded that,
“The finding that varenicline decreased ethanol consumption in chronically exposed ethanol-consuming rats suggests that varenicline may serve as a therapeutic treatment to reduce alcohol consumption in alcoholic subjects; however, this remains to be examined.”

This means that these results in animals are suggestive of a potential effect in humans, but proper clinical trials in humans will be needed. So these reports of reduced interest in drinking alcohol among people taking Chantix for smoking cessation, may have a real pharmacological basis that may ultimately be clinically useful for people with alcohol problems.

The full study can be viewed at:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17626178

Labels: alcohol problem relapse, champix, Chantix, jonathan foulds, smoking cessation, 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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New study compares Chantix to the nicotine patch

We have already talked about the studies showing that Chantix (varenicline or Champix outside the US) is more effective than both placebo pills and Zyban (bupropion) for smoking cessation. There has also been one study comparing smoking cessation outcomes before and after Chantix was available (by John Stapleton and colleagues in the UK).

Today a new study has been published comparing the effects of a standard course of Chantix (12 weeks) with a normal course of the nicotine patch (10 weeks) for stopping smoking. This was a randomized “open-label” study, meaning that neither the participants nor the researchers were able to choose which participants got which treatment, (they were allocated to treatment on the basis of random numbers), but that everyone new which treatment they got (i.e. there were no placebo or dummy patches or pills).

The study by Aubin and colleagues was carried out across 5 countries (Europe and USA), with 376 smokers being assigned to Chantix and 370 to the patch. All the participants smoked at least 15 cigarettes per day (average = 23 per day). The participants were required to be relatively healthy with no unstable illnesses within the previous 6 months (including psychological problems or substance dependence). None had used nicotine replacement therapy in the previous 6 months. About half (48%) had previously tried the nicotine patch, and almost 90% had previously tried to quit. The average age of participants was 43, and they had smoked for around 26 years. 93% of the participants were white.

Participants attended weekly appointments for the first 12 weeks, then had 7 further appointments up to the one year follow-up, as well as 5 telephone contacts.

3 months after the target quit date, 56% of those treated with Chantix had not used any tobacco during the prior month, as had 42% of those treated with the nicotine patch. This advantage for Chantix treatment was statistically significant. At the one year follow-up (i.e. after about 9 months without treatment medications) 26% of those allocated Chantix treatment remained remained quit, as did 20% of those treated with the patch (also a statistically significant difference). During the first 7 weeks of treatment, those treated with Chantix reported significantly lower craving, negative affect (bad mood) and restlessness.

About twice as many patients treated with Chantix (8%) as the patch (4.3%) had to discontinue the medicine due to an adverse event. The most frequent adverse events were nausea (37% on Chantix versus 10% on the patch), insomnia (around 20% in both groups) and headache (19% Chantix, 10% patch).

There has been some recent concern (discussed on this forum) about Chantix potentially causing depression and suicidal thoughts. In this trial, one person became depressed and it was believed to be caused by Chantix, and another person had suicidal thoughts (causing hospitalization) 11 days after completing Chantix treatment. These low rates of serious depression (<1%) in association with Chantix treatment are consistent with prior reports. It is interesting that ratings of “negative affect” were significantly lower among those taking Chantix than the patch during the first 7 weeks (meaning that Chantix users experienced, on average less bad moods/depressive thoughts than those wearing the patch). So the etiology of depression while taking Chantix remains a mystery. One possibility is that Chantix, because it is slightly more effective than prior medications, enables some people to successfully quit who would not otherwise have succeeded, and some of those people may be more prone to depression in association with quitting smoking.

Overall, the results from this study are consistent with previous studies in showing that Chantix is probably the most effective single medicine for smoking cessation, that it frequently causes mild side effects (e.g. transient nausea) and that serious adverse events are uncommon.

Ref:
Aubin HJ et al. Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomized, open-label trial. Thorax published online Feb 8, 2008.

Labels: cessation, Chantix, cigarette smoking, jonathan foulds, Nicotine Replacement, patch, varenicline

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Planning to quit smoking with Chantix

We are currently approaching the peak “New Year” season for quitting smoking – also a time when people are very busy finishing off their year-end work and participating in the holiday season. As Chantix is the newest medication designed to help people quit, and will likely be heavily advertised by Pfizer – its manufacturer, I expect hundreds of thousand of people will use it for the first time over the coming months.

However, as we have discussed at length on this forum, some concerns have emerged regarding potential adverse events relating to use of this medicine: depressive or suicidal thoughts, aggressive or erratic behavior and drowsiness.
See link for prior discussions: http://www.healthline.com/blogs/smoking_cessation/2007/11/chantix-varenicline-safety-being.html

So is this a good drug that may help save your life or a dangerous drug that may harm you? As we’ve discussed before, the evidence is clear that Chantix is effective at helping smokers quit and is typically accompanied by fairly mild side-effects (e.g. mild nausea). The concerns are over the possibility that a very small minority of Chantix users (perhaps between 0.1 and 1%) may experience the more serious side-effects mentioned above. At the moment the FDA is investigating this, but so far there is no conclusive evidence that these side effects are caused by Chantix (rather than being rarely occurring effects of stopping smoking). I therefore recommend that smokers interested in quitting should not be scared to try Chantix as the drug really does help smokers quit. But I strongly recommend that smokers planning to use Chantix should ensure that they have organized a proper quit plan, utilizing a number of support networks (e.g. telephone quitline, family etc) but very much involving the family doctor also. By this I mean that rather than simply calling in to the doctor for a prescription (or ordering it on a website), you arrange an appointment with your doctor to discuss the use of the medicine, and its potential side-effects, and that you also arrange at least one follow-up appointment with him/her within the first two weeks of starting on the medicine. If a doctor who knows you and your medical history is supporting your quit attempt and monitoring your progress it is far less likely you will be seriously affected by these potential side effects, and more likely you will succeed in quitting.

This model of quitting smoking is also precisely what is recommended by the Clinical Pratice Guideline your doctor should be following (advising doctors on the “5 As”: Ask, Advise, Assess, Assist, Arrange)
http://www.tobaccoteacher.com/5As.html

So my recommendation for people thinking of trying Chantix in the near future is that you should start planning now. This would involve making an initial appointment to see your doctor, planning a target quit date (just over a week after your doctors appointment) AND arranging an additional follow-up appointment shortly after your quit date, so your doctor can monitor progress and give advice. These steps should be taken in addition to using other assistance such as telephone quitlines and internet sites for smoking cessation, enlisting the support of family and friends, and taking other sensible behavioral steps (e.g. throwing out all your remaining tobacco the night before your quit date).

Best of luck, and have a great holiday season.

Labels: cessation, Chantix, cigarette smoking, holidays, jonathan foulds, new year

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New study of Chantix in comparison with NRT

Recently there has been some concern over side-effects experienced by a minority of people using Chantix (varenicline). Although Chantix had a remarkably good safety and efficacy record in the clinical trials conducted prior to its launch, those trials excluded patients with complex medical or psychiatric problems (normal practice in pre-approval clinical trials). So when a number of patients (albeit a tiny proportion of the millions who have used Chantix) have reported unpleasant and serious mood disturbances or even suicidal thoughts and acts while taking Chantix since it was launched, this has led to a concern that perhaps Chantix may have more serious side-effects in regular patients with complex medical and psychiatric problems.

A new study by John Stapleton and colleagues was published this week in the journal, Addiction, that addressed this issue. The study reports on the clinical outcomes of 412 patients being treated at a tobacco dependence clinic in London, UK. 204 patients were treated with nicotine replacement therapy (NRT) between May and November, 2006 (prior to Chantix being launched in the UK), and 208 patients were treated with Chantix from January to April 2007. Although the two groups were not randomly allocated to treatments, they were very similar on a number of baseline measures - for example 47% of those treated with NRT were men and 50% of those treated with varenicline were men. The daily cigarette consumption of the two groups was 21 and 22 cigarettes per day respectively. The only signs of baseline differences between the groups were that 69% of those treated with NRT were white, compared with 79% of those treated with Chantix. Those treated with Chantix also rated themselves as being slightly more “determined to quit” at baseline. All of the patients were treated in weekly stop-smoking groups for 7 weeks, with the target quit date coming at the third group meeting. Some of the patients using NRT used “combination” NRT (typically the patch plus either nicotine gum, lozenge, nasal spray or inhaler). At the end of group treatment (i.e. four weeks after the target quit date), 66% of those using a single NRT, 75% of those using combination NRT and 80% of those using Chantix were no longer smoking (not a puff in the previous two weeks). So Chantix produced higher quit rates than a single NRT product, but similar to combination NRT.

111 of these patients were receiving treatment for a mental illness, and the pattern of results for those patients was similar to that of the group as whole, with higher quit rates for those using Chantix. In the whole sample, those using Chantix reported significantly lower craving scores, with no differences on ratings of withdrawal symptoms (e.g. irritability, poor concentration, etc).

An analysis of adverse drug reactions found only one that was more commonly reported with NRT than with Chantix (skin irritation related to patch use). However, 12 symptoms were reported more frequently among those using Chantix. Those symptoms were, nausea (38%), disturbed sleep (30%), vivid dreams (13%), drowsiness (12%), constipation (11%), headache (10%), dyspepsia (8%), dry mouth (7%), bad taste (7%), depression/low mood (5%), diarrhoea (5%), and disorientation/confusion (5%). 7 patients reported moderate/severe anxiety/panic while on Chantix, compared with only one on NRT. Two patient had adverse reactions while using Chantix that were of sufficient severity to be reported to the Medicine’s Regulatory Authority in the UK. One of these was for a “severe psychological reaction likened to a bad LSD trip, including anxiety, paranoia, and confusion.”

It should be noted that around 80% of the patients in this study had previous experience trying to quit smoking using NRT. It is possible that those taking the new drug (Chantix) would have a stronger tendency to note side effects than those using an NRT that they were familiar with.

Overall, these results are broadly consistent with the evidence from clinical trials and post-launch clinical experience with Chantix. They are consistent with the ideas that (a) Chantix may result in slightly higher chances of success in quitting smoking than another single medicine/NRT (b) Quitting success rates on Chantix are broadly similar to those with combination NRT, (c) Chantix results in more side effects than NRT, of which some are common (e.g. nausea, disturbed sleep and vivid dreams) and some less common (<5%) – including depressed mood, disorientation and anxiety. The single patient experiencing a severe psychological reaction while using Chantix may be an indication that such reactions can occur but are rare (<1%).

It should be noted that all of the patients in this study were being treated in a specialist tobacco treatment clinic, within the context of support groups facilitated by experienced clinicians. In that context adverse effects of medications can be monitored, and if necessary patients promptly switched to different medications. Many of the psychological side effects were 3-5 times more common among patients using Chantix than among patients using NRT.

The research continues to show that Chantix is an effective drug for smoking cessation, that offers renewed hope for those who have tried and failed with other treatments. However, I think patients who are not planning on maintaining regular contact with an experienced clinician during their quit attempt (i.e. a clinician who can monitor side effects and provide supportive advice on a regular basis) should give serious consideration to using combination NRT (patch plus one other NRT) as a first choice. This treatment has the advantage that the patient is not taking a “new drug” – just the same one (nicotine) they have been taking, but without the 4000 other toxic chemicals.

Labels: Chantix, cigarette smoking, foulds, nicotine, NRT

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Chantix (varenicline) safety being reviewed by FDA

The issue of Chantix safety and particularly its potential psychiatric side effects have been previously discussed on this blog with many informative comments from Chantix users and their family members:
"Chantix: how does this new stop smoking medicine work?” 4/15/07
http://www.healthline.com/blogs/smoking_cessation/2007/04/chantix-how-does-this-new-quit-smoking.html
“Chantix and mental illness: what are the facts?” 08/12/07
http://www.healthline.com/blogs/smoking_cessation/2007/08/chantix-and-mental-illness.html
“Two new studies of Chantix (varenicline)”. 8/19/07
http://www.healthline.com/blogs/smoking_cessation/2007/08/two-new-studies-of-chantix-varenicline.html
"Does Chantix cause mental health problems?" 9/20/07: http://www.healthline.com/blogs/smoking_cessation/2007/09/does-chantix-cause-mental-health.html
Immediate and delayed quitting. 10/14/07: http://www.healthline.com/blogs/smoking_cessation/2007/10/immediate-and-delayed-quitting.html

On November 20th, the US Food and Drug Administration issued an announcement regarding an ongoing safety review of Chantix, focusing on potential effects on suicidal thoughts, aggressive behavior and drowsiness. The full text of yesterday’s announcements by FDA are attached in quotes below.
This will likely get some more headlines in the media and it is important that consumers and patients understand what this announcement means, and don’t over-react.
This “early communication” is simply stating that FDA are analyzing additional data on the potential link between Chantix and these potential side-effects. It has not concluded that there is any causal relationship and FDA is not recommending that doctors stop prescribing Chantix, nor that patients stop taking it, unless they have reason to believe that they are starting to experience potentially dangerous side effects of the medication,. In that case patients should discuss this with their doctor, bearing in mind that irritability and depression are nicotine withdrawal symptoms that commonly occur on stopping smoking without any medication. The FDA announcements are inside the quotation marks below:

“Chantix (Varenicline)
Audience: Healthcare professionals, consumers[Posted 11/20/2007]
FDA informed healthcare professionals of reports of suicidal thoughts and aggressive and erratic behavior in patient who have taken Chantix, a smoking cessation product. There are also reports of patients experiencing drowsiness that affected their ability to drive or operate machinery. FDA is currently reviewing these cases, along with other recent reports. A preliminary assessment reveals that many of the cases reflect new-onset of depressed mood, suicidal ideation, and changes in emotion and behavior within days to weeks of initiating Chantix treatment. The role of Chantix in these cases is not clear because smoking cessation, with or without treatment, is associated with nicotine withdrawal symptoms and has also been associated with the exacerbation of underlying psychiatric illness. However, not all patients described in the cases had preexisting psychiatric illness and not all had discontinued smoking. Healthcare professionals should monitor patients taking Chantix for behavior and mood changes. Patients taking this product should report behavior or mood changes to their doctor and use caution when driving or operating machinery until they know how quitting smoking with Chantix may affect them. [November 20, 2007 - Ongoing Safety Review: Varenicline (marketed as Chantix) - FDA][November 2007 - Prescribing Information - Pfizer] :”

“This information reflects FDA’s current analysis of available data concerning these drugs. Posting this information does not mean that FDA has concluded there is a causal relationship between the drug products and the emerging safety issue. Nor does it mean that FDA is advising health care professionals to discontinue prescribing these products. FDA is considering, but has not reached a conclusion about whether this information warrants any regulatory action. FDA intends to update this document when additional information or analyses become available.
FDA has received reports of suicidal thoughts and aggressive and erratic behavior in patients who have taken Chantix, a smoking cessation product.
Suicidal Thoughts
The manufacturer of Chantix, Pfizer, Inc., recently submitted to FDA postmarketing cases describing suicidal ideation and occasional suicidal behavior. FDA currently is reviewing these cases, along with a number of recent reports in the popular press and internet sites. A preliminary assessment reveals that many of the cases reflect new-onset of depressed mood, suicidal ideation, and changes in emotion and behavior within days to weeks of initiating Chantix treatment. The role of Chantix in these cases is not clear because smoking cessation, with or without treatment, is associated with nicotine withdrawal symptoms and has also been associated with the exacerbation of underlying psychiatric illness. However, not all patients described in these cases had pre-existing psychiatric illness and not all had discontinued smoking.
Aggressive and Erratic Behavior
FDA is aware of a highly-publicized case of erratic behavior leading to the death of a patient using Chantix to attempt to quit smoking. Although other factors, including alcohol consumption, appear to have played a part in this specific case, FDA asked Pfizer for additional cases that might be similar. We are currently evaluating the material Pfizer submitted in response to our request.
Drowsiness
FDA is evaluating reports from Pfizer of drowsiness in patients taking Chantix. Reports described patients who experienced drowsiness that affected their ability to drive or operate machinery.
FDA recommends the following:
Healthcare professionals should monitor patients taking Chantix for behavior and mood changes. Patients taking Chantix should contact their doctors if they experience behavior or mood changes. Patients should use caution when driving or operating machinery until they know how quitting smoking with Chantix may affect them.

This early communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs. FDA is working with Pfizer, Inc., to further evaluate the potential association between Chantix and suicidal thoughts, aggressive and erratic behavior, and impairment that affects one’s ability to drive or operate machinery. FDA is working to complete the analysis of the materials submitted by Pfizer. As soon as this analysis is completed, FDA will communicate its conclusions and recommendations to the public.

The FDA urges both healthcare professionals and patients to report side effects from the use of Chantix to the FDA's MedWatch Adverse Event Reporting program
online at www.fda.gov/medwatch/report.htm
by returning the postage-paid FDA form 3500 available in PDF format at www.fda.gov/medwatch/getforms.htm to 5600 Fishers Lane, Rockville, MD 20852-9787
faxing the form to 1-800-FDA-0178
by phone at 1-800-332-1088 “

Labels: Chantix, cigarette smoking, foulds, varenicline

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Immediate and delayed quitting

Last week I attended the 4th annual meeting of the Society for Research on Nicotine and Tobacco (Europe) in Madrid. This is a conference where the top researchers present their latest research findings. As you can imagine a lot of fascinating stuff was presented. One that I particularly liked was presented by David Gonzales of the Health and Sciences University in Portland. He presented data on immediate quitting (i.e. those who succeeded in quitting on their target quit date with no lapses) and delayed quitting (i.e. those who had some lapses after the initial target quit date but then managed to get quit and stay quit) among patients treated with either varenicline (Chantix), bupropion (Zyban), or placebo.

For me the interesting thing was that Chantix and Zyban each improved the proportion who initially quit (over placebo), but Chantix also increased the proportion who managed to achieve abstinence after their initial target quit date. Dr Gonzalez presented a nice diagram showing that the number of patients achieving abstinence continued to increase across the first 12 weeks among those on Chantix or Zyban (although it increased faster among those on Chantix).

Colleagues have remarked that patients taking Chantix are less focused on the target quit day (typically day 8 of taking Chantix) than we are used to. We think that’s because almost all of the patients we treated before Chantix were also using nicotine replacement therapy (sometimes combined with Zyban/bupropion). The NRT (patch, gum etc) is typically started on the target quit day and so patients are very aware of the importance of that day. We don’t typically combine Chantix with NRT (as the Chantix is supposed to block the nicotine receptors in the brain) and so on Chantix its easier to see the target quit date as less distinct from any other day and just continue reducing cigarette consumption rather than quitting completely.

The take-home message for patients is that it still makes sense to select a target quit-date (day 8) and to try to quit smoking completely on that day. However, if you don’t immediately get quit, don’t give up on yourself or on the medicines. The evidence suggests that if you keep trying you will likely achieve abstinence, and that Chantix improves your chances, so long as you keep trying and keep taking the medicine. On the other hand, its important to be clear that the aim of the game is to quit completely, and its better in the long run to throw away the cigarettes and get on with it.

Labels: bupropion, Chantix, cigarette smoking, quit, varenicline, Zyban

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Does Chantix Cause Mental Health Problems?

The issue of Chantix effects on mental health gained national attention yesterday when the ABC News program “Good Morning America” covered the story of the bizarre and tragic death of the Texas musician, Carter Albrecht. http://www.abcnews.go.com/GMA/OnCall/Story?id=3623085&page=2

Some of the details of this tragedy can be found online via the ABC news story but the key points were that Mr Albrecht was actually killed by being shot in the head by a neighbor as he banged on the neighbor’s door, but that his girlfriend felt that his bizarre behavior may have been caused by the Chantix he was taking at the time.

Regular readers of this blog will know that this issue has come up before – see:
“Chantix: how does this new stop smoking medicine work?” 4/15/07
http://www.healthline.com/blogs/smoking_cessation/2007/04/chantix-how-does-this-new-quit-smoking.html

“Chantix and mental illness: what are the facts?” 08/12/07
http://www.healthline.com/blogs/smoking_cessation/2007/08/chantix-and-mental-illness.html

“Two new studies of Chantix (varenicline)”. 08/19/07
http://www.healthline.com/blogs/smoking_cessation/2007/08/two-new-studies-of-chantix-varenicline.html

There have been a number of comments from people who experienced frightening dreams, anxiety attacks, depression and suicidal thoughts while on the medicine, as well as the suicide of a family member. The number and pattern of these comments were sufficient to cause me some concern and so I decided to take another look at the published reports of the clinical trials of Chantix and also speak to a number of colleagues who treat many patients with Chantix, in order to try to get a sense of whether these experiences may be caused by Chantix, rather than other potential causes (including nicotine withdrawal effects).

On looking at the evidence from the clinical trials, it is more consistent with the idea that Chantix reduces depressive thoughts, rather than increases them. For example, one large study was published in JAMA on July 2006 comparing the outcomes of 352 smokers treated with Chantix (varenicline), 329 people treated with Zyban (bupropion) and 344 people treated with identical placebo pills. This was a randomized double-blind trial meaning that no-one knew which type of pills they received until the end. 22% quit completely for a year on Chantix, as did 16% on Zyban and 8% on placebo. The paper reported on changes in “negative affect” (a combination of unpleasant mood symptoms including depression and irritability). Patients on Chantix reported a significantly SMALLER increase in these symptoms than patients taking placebo. Zyban had a similar effect of reducing negative affect compared with placebo pills. The paper also listed adverse events reported by participants. The main symptom that was clearly reported more frequently by Chantix users was nausea, reported by 28% of Chantix users, compared with 13% on Zyban and 8% on placebo. Of the psychiatric disorders mentioned, only “abnormal dreams” appeared to be more common on Chantix (10%), compared with 6% on Zyban and 6% on placebo. There was no clear difference in reports of serious irritability (6%, 5%, 6%) and fewer patients on Chantix reported insomnia (14%) than did patients on Zyban (22%). In terms of “serious” adverse events, these were no more common for Chantix than placebo and the single case of a serious psychiatric event (acute exacerbation of schizophrenia) occurred in a patient taking placebo pills.

Another almost identical trial was reported by Jorenby and colleagues in the same issue of JAMA, with very similar results (i.e. higher quit rates with Chantix, along with lower reported negative affect [mood] than placebo, but higher rates of nausea.). Serious adverse events again were rare and scattered evenly across the different types of pills with little clear pattern, but there was one report of “acute psychosis, emotional lability” in the Chantix group (out of 344 taking Chantix). This study did, however, find a higher rate of “abnormal dreams” on Chantix (13%) than Zyban (6%) or placebo (4%). The earlier studies designed to identify the best dose of Chantix also had similar findings (dose-dependent increase in nausea and abnormal dreams) but no real evidence of other mental health symptoms. For example, Nides and colleagues found 10% on placebo and 12% on the high dose of Chantix reported serious “irritability’, and that “depression was not observed as an adverse event with varenicline (Chantix) treatment.”

The data sheet for prescribers of Chantix notes that 4500 people were exposed to Chantix during its premarketing development and that discontinuation of treatment due to adverse events was rare. The most frequent reason was nausea (3% for Chantix versus 0.5% for placebo). 0.3% reported discontinuing Chantix because of abnormal dreams as did 0.2% on placebo pills. As with all medications, the data sheet has a long list of symptoms experienced by participants in the trials, including “Psychotic disorder, suicidal ideation” as “rare”. Note – this does not imply that the drug caused these events – just that they occurred rarely in people taking the drug. Overall, the pattern of results from trials of Chantix suggest that with the exception of abnormal or vivid dreams, psychiatric symptoms such as depression or negative affect are LESS likely to occur in people taking Chantix to quit smoking, than in people taking placebo pills while quitting smoking.

However, one has to bear in mind that early clinical trials typically exclude patients currently being treated for mental health and other serious health problems. So the possibility remains that the drug may cause problems in types of patients that were not included in the initial trials. That’s where post-marketing surveillance is important. This is something that the pharmaceutical companies and doctors routinely carry out. For my part, I simply asked a large group of colleagues who are experienced in treating “real patients” with Chantix and other treatments, whether they had noticed any signs of worsening mental health associated with Chantix use. The clinicians I spoke to estimated that they had been involved in the treatment of over 2000 patients with Chantix, including patients with co-occurring serious mental health and other medical problems. There was a pretty clear consensus that while there were a few isolated cases (a couple) of patients reporting mental health problems, these were not noticeably more frequent than one normally encounters with other treatments (e.g. nicotine replacement or Zyban, or counseling with no medication).

So overall I am somewhat reassured that Chantix is a safe medicine that is effective at helping smokers to quit. But why the rash of reports on the internet of depression and bizarre behavior? Firstly, I don’t doubt that these people’s experiences are real and in some cases, very serious. I also think it is plausible that some (probably a minority) could be directly linked to Chantix. In some cases it could be an unusual interaction between the individual, the medicine and maybe another drug (including alcohol) they are taking. But for most, I suspect the serious behavioral/psychiatric problems experienced are unlikely to be caused by Chantix. Here are my reasons:
1. For highly addicted smokers, mood disturbance and altered thinking is common when quitting smoking, even without taking any medication.
2. The evidence described above, indicates that with the exception of abnormal dreams, Chantix reduces the severity of mood/psychological disturbance experienced while trying to quit smoking.
3. Around 3 million Americans have taken Chantix to try to quit smoking. Among that many smokers trying to quit for a month or two, one would expect a few thousand or more to have serious symptoms of depression etc even if they were not taking a medicine to help them. But when someone has these symptoms while taking a new drug, it is perfectly natural to conclude that the drug may have caused the symptom. In these days of widespread internet access, chat-rooms etc, that easily turns into a few hundred patients reporting similar symptoms on the internet while taking the same drug.

It therefore appears that if Chantix causes any serious mental health problems at all (which remains unproven), it is extremely rare (perhaps in the order of one per thousand). So my advice is that if you are considering quitting smoking and are interested in taking an FDA-approved medicine, whether it be nicotine replacement therapy, bupropion or Chantix, then you should not be put off by relatively isolated reports of side effects. The highest quality of evidence (from randomized placebo-controlled trials) demonstrates that these medicines are safe and will roughly double your chances of successfully quitting smoking. However, everyone reacts to medicines differently, and if you start to experience a worrying symptom that you believe may be caused by the medicine you should consult your doctor immediately. Even better, when you see your doctor to obtain a prescription, you should arrange a follow-up visit within a week or so of starting the medicine in order to discuss your progress, side-effects etc. If you have any concerns between appointments, call your doctor. It is also wise to get as much additional support from friends, family, telephone quitlines etc as possible. There is a national (US) toll-free number for telephone counseling (1-877-448-7848) and in the case of Chantix users in the US, there is additional support available via http://www.chantix.com/ .

Finally, anyone who believes there to be a causal link between use of a medication and a severe adverse event (e.g. depression, suicidal ideation, suicide, or any other serious adverse event), whether it be in yourself, your patient or a family member, should report it to the MedWatch program at: http://www.fda.gov/medwatch/how.htm . This is one of the main mechanisms of post-marketing surveillance that can help identify rare or previously unknown risks from medicines.

Labels: cessation, Chantix, cigarette smoking, varenicline

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Getting through the first few weeks

When people quit smoking it is very common for them to experience a temporary increase in certain unpleasant symptoms. The most common nicotine withdrawal symptoms are:
1. Irritability
2. Restlessness
3. Poor concentration
4. Depression
5. Increased appetite
6. Anxiety
7. Insomnia

I discussed these symptoms in previous posts:
What is nicotine withdrawal syndrome? 3/6/07
http://www.healthline.com/blogs/smoking_cessation/2007/03/what-is-nicotine-withdrawal-syndrome.html

Ten tips for coping with nicotine withdrawal. 3/7/07
http://www.healthline.com/blogs/smoking_cessation/2007/03/ten-tips-on-coping-with-tobacco.html

However, I’m bringing this topic up again because I’m noticing a number of people trying to quit smoking by using Chantix who are still experiencing some of the symptoms mentioned above but are concluding that these symptoms are caused by the medicine. Of course with any individual person the best way to figure out the cause of a new or worsening symptom is to discuss the problem in detail with your health professional. But in general, if someone has just quit smoking and they experience one of the symptoms mentioned above, the first explanation to consider is that it is a temporary nicotine withdrawal symptom caused by stopping smoking, rather than a symptom caused by a smoking cessation medicine.

Sometimes similar symptoms can be caused by smoking cessation medicines. For example, insomnia and vivid dreams can also be caused by the 24 hour nicotine patch and by bupropion (Zyban or Welbutrin). Chantix has also been known to cause vivid dreams. Generally, the heavier a smoker the person is, the more likely they will be to experience strong withdrawal symptoms, and the less likely their symptoms are caused by their medication. The opposite is also true. So if a 40-a day smoker experiences insomnia 2 days after quitting smoking while taking the standard dose of a smoking cessation medicine it is more likely to be due to nicotine withdrawal. If a 10 cigarettes per day smoker who never wakes at night to smoke and doesn’t smoke within half an hour of waking in the morning experienced the same insomnia it is might be caused by the medicine. In the case of the patch, they might want to try taking it off a few hours before going to bed, and in the case of Zyban or Chantix they might want to make sure they don’t take the second pill just before going to bed.

My main point here, however, is to caution against blaming the medicine for symptoms that it may actually be helping with, and then stopping using the medicine too soon. Any change in timing or dosage of a medicine should be discussed with your doctor first.

Similarly, it is tempting when a medicine is not giving complete relief of unpleasant symptoms like insomnia, anxiety or cravings to want to try another medicine as well. As always, a decision on what medicines are most likely to help you in any specific situation is best made after a full discussion between you and your doctor. However, when one of the symptoms mentioned above is the problem, and particularly if you were a heavy smoker and have recently quit, then the symptom is likely caused by nicotine withdrawal and will resolve by itself gradually over a couple of weeks. Medicines that have not been approved by the FDA or a similar medicines regulatory authority for smoking cessation will be unlikely to help much.

To tell if you are a “heavy smoker” check out my previous posts on that topic:
How addicted are you to cigarettes? (1) 5/19/07
http://www.healthline.com/blogs/smoking_cessation/2007/05/how-addicted-are-you-to-cigarettes-1.html

How addicted are you? (2) 5/19/07
http://www.healthline.com/blogs/smoking_cessation/2007/05/how-addicted-are-you-2.html

If you are a heavy smoker and are having a rough time quitting I’d strongly encourage you to get as much support as you possibly can. As well as speaking to your own personal health professional, I’d recommend a specialist face-to-face tobacco treatment service if there is one near you (they will have experts in smoking cessation counseling and medicines), as well as use of smoking cessation telephone helplines and internet sites, that were also discussed in previous posts:

Telephone quitlines: do they help smokers to quit? 4/19/07
http://www.healthline.com/blogs/smoking_cessation/2007/04/telephone-quitlines-do-they-help.html

Can smoking cessation internet sites help you to quit? 4/21/07
http://www.healthline.com/blogs/smoking_cessation/2007/04/can-smoking-cessation-internet-sites.html

Key things to remember during the rough times are:
A. Nicotine withdrawal symptoms are worst during the first couple of weeks after you completely quit tobacco and gradually calm down to be almost gone by the 4th week.
B. Each individual episode of craving for a cigarette typically lasts a few seconds, and rarely longer than a couple of minutes. Keeping yourself busy and actively switching your mind onto other things will help get rid of cravings more quickly.
C. Cravings are stimulated by being around tobacco and other people smoking. If you have any in the house, get rid of it. If you are hanging out in a place where people are smoking, hang out somewhere else!

You have probably put in quite alot of effort by the time you found this web-site. Don't throw it away by having a smoke. Keep going. It is tough but you can succeed.

Labels: Chantix, cigarette smoking, nicotine, patch, quitting, side-effects, symptoms, withdrawal, Zyban

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