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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Comment on FDA Advisory on varenicline and bupropion

In my previous post I summarized the new information from FDA on varenicline and bupropion for smoking cessation. Before giving my opinion on this, there are a couple of things Id like to point out. The first is that I have done paid consulting work for the manufacturers of varenicline (Pfizer) and some brands of bupropion (GSK) as well as other companies marketing competing medicines (e.g. Novartis and Celtic Pharma). The second is that I take very seriously the major adverse events that some people have experienced while taking these medicines (and while attempting to quit smoking without these medicines). A number of family members of people who have committed suicide while taking these medicines have commented online on earlier posts on this blog, as have others who experienced marked mood changes. So one cannot help but be affected by hearing these stories and seek to understand what might be going on. In particular I think it is important to examine all the evidence, both from individual case histories and from analyses of larger clinical trials and population datasets, in order to try to form an opinion as to what may have caused the adverse events.

I also understand that those working for FDA who have to examine all the reports they have received, cannot help being affected by these also. A New York Times article published on July 1 stated that FDA had reports of 98 completed suicides in connection with varenicline (Chantix). Suicide is always an enormous tragedy and it is understandable that those reading the reports would be left feeling that they have to do something.

I have written previously on this issue, and you can find my previous posts by writing the appropriate search term (e.g. Chantix, varenicline, depression, bupropion or nicotine withdrawal) in the box on the right where it says, “search health experts”.

The first thing that has to be borne in mind is that mood disturbance is a normal part of nicotine withdrawal. Like most things, individuals vary in how severe that mood disturbance is, and for a small percentage it can be severe. Depression is just one of 8 recognized nicotine withdrawal symptoms. Here are some comments that readers of this blog made in response to my post on June 17, 2007 on, “Can quitting smoking trigger depression?”:

“I truly believe quitting can trigger depression. In fact, I am now 39 and have spent most of my 30's trying to quit. Have quit 4 times in the last nine years - twice for 9 months, once for 18 months and have not smoked now since New Year's Eve - so about 5 months. Physically I feel much better, no coughing in the morning, but mentally, I feel terrible.. Each time I have gone back to smoking it has been due to the hideous depression I suffer whilst not smoking. I alienate my friends and family - I feel so low, I am unable to string a sentence together at times, let alone motivate myself to leave the house. Work is a struggle as I work in an office and have to interact with others - love the weekends when I can shut myself away from the world.”

“I quit smoking 8 weeks ago. After consulting with my GP, because I've suffered from depression before (I came off antidepressants about 6 months ago after being on them for over 2 years!) and because every time I've tried quitting smoking before have been hit really badly by a bad bout of temporary depression from nicotine withdrawal, I started using patches and an inhalator for when I needed an extra 'boost' of nicotine to try to alleviate the depressive symptoms gradually.

The first 6 weeks on the 15mg patches was surprisingly easy and, apart from a couple of grumpy periods which lasted no longer than an hour or two at most, I didn't have the usual massive slump in my mood . I even succumbed whilst drunk to 1 cigarette about 3 weeks into my quit, but it tasted absolutely foul and I stubbed it out before I'd finished it - "this time" I thought, "I've really managed to do it".

But then I moved down to the 10mg patch, which coincided with a family holiday to the seaside...a time that I thought would be ideal for stepping down to less nicotine, as I'd be away from the day-to-day stresses of life & work. But unfortunately I just found that I was hit by a MASSIVE bout of depression - as bad as anytime that I've tried quitting cold turkey. I'm very wary of the 'danger signs' of my depression now and so, after a week where our family holiday was, frankly, pretty hellish all round, I succumbed to the fags again purely as I knew it would (even temporarily) alleviate the depression. After 2 evenings and a day of being back on the fags, I decided that I really didn't want to carry on smoking, as the sore throat and very stuffy nose that I've always had whilst smoking had come back, and getting rid of that had been one of the really strong reasons for quitting in the first place! So now I'm trying the 10mg patches again, and whilst yesterday I was pretty grumpy and stressed, I'm trying to put a more positive thought on things today in the hope that things will improve. If not, I'm considering whether going back onto antidepressants for a while would help, but it does make me wonder which is the lesser of two evils - the dangers of smoking, or the dangers of mental illness by not smoking!”

“I am approaching 6 months smoke free the end of march, after smoking heavy for 26 yrs. i went through the horrible depression, the uncontrollable crying, the overwhelming sense of nothingness and wothlessness in my life. did not want to get out of bed most days.”

These are posts by people trying to quit smoking who were not using varenicline (Chantix) or bupropion. The point here is that some people get depressed when they stop smoking. 11 million people have used varenicline as part of their attempt to quit smoking, with more than half of them in the United States. So it should be no surprise that when such a vast number of people use a drug to try to quit smoking, that a large number (even if only a very small proportion) report their experiences as side effects of the drug.

However, we also need to look at the thorough studies that have examined this issue in a systematic manner, for signs that these medicines could be actually causing some cases.

Earlier this year Kasliwal and colleagues in the UK reported (in the journal, Drug Safety”) on a cohort of 2682 varenicline users they have been following. The majority of people who stopped using the drug due to a side effect did so due to nausea or vomiting (n=91). The most frequently reported psychiatric events (causality not implied) were sleep disorder (n=43, 1.6% of the cohort), anxiety (n=33, 1.2%), depression (n=29, 1,1%), abnormal dreams (n=26, 1.0%) and mood change (n=17, 0.6%). 2 cases of attempted suicide wee reported during treatment with varenicline. Both of these patients had a previous history of psychiatric illness and precipitating factors for the event.

John Stapleton, another researcher in the UK, published in the journal, “Addiction” an analysis attempting to answer the question, “Do the 10 UK suicides among those taking the smoking cessation drug varenicline suggest a causal link?”. Stapleton noted that these 10 suicides occurred over the 21-month period from December 2006 to August 2008. He also noted that there are about 5500 suicides each year in the UK among those aged 15 or older, and that around 2000 of these are in smokers (or 3500 over the 21 months of the period under study). During that time around 5% of UK smokers tried varenicline, (n=500,000). On average, one would therefore expect about 175 suicides in 21 months among the 500,000 people who used varenicline. But of course they did not take varenicline for the full 21 months. Stapleton assumed that the typical varenicline user took the drug for only 6 weeks, and calculated that 12 suicides would be expected by chance among people taking varenicline, (i.e. slightly more than were actually reported). He concluded that,
“the UK data do not appear to suggest even an association between varenicline and suicide, far less a causal link.”

At a recent conference, Professor Serena Tonstad presented an analysis of adverse events in all 9 placebo-controlled trials of varenicline that were published by the end of 2008. Some of these trials also included patients randomized to treatment with bupropion. This analysis found the rate of suicidal behavior to be 0/2783 (0%) for varenicline, 1/795 (0.001 %) for bupropion, and 2/1655 (0.001 %) for placebo. Clearly no evidence that either drug cause an increased rate of suicidal behavior. But people with a recent history of psychiatric problems were excluded from those trials.

In the May 2009 issue of Annals of Pharmacotherapy, Purvis and colleagues reported on the safety and effeciveness of varenicline in a Veteran population with a high prevalence of mental illness (almost 50%). They followed 50 veterans for 12 weeks through their quit attempt with varenicline. 30% quit smoking, but the quit rate was lower in those whose partner also smokes or who had a mental illness. All 5 patients who reported mood or behavioral changes that they attributed to varenicline had a pre-existing psychiatric problem (all had depression, 2 also bipolar, one of whom successfully quit). So this study suggests a higher rate of behavioral problems on varenicline among those with current psychiatric problems, but still doesn’t point clearly to a causal effect.

There have been other publications on varenicline over the past year, including some reports of psychiatric effects, and one case report of a woman who smoked 50 cigarettes per day who had suffered depression with suicidal tendencies on prior quit attempts without varenicline, but who was finally able to quit successfully with varenicline and inpatient treatment.

Overall, my take on this evidence is that mild to moderately severe nicotine withdrawal symptoms are the norm for regular smokers trying to quit without any medicine. A small percentage (probably less than 1% ) of those who stay quit for more than a couple of weeks develop more severe effects, that may include depression and suicidal thinking. While both varenicline and bupropion are known to cause some side effects (e.g. nausea or sleep disturbance) it remains unclear and I’d say unlikely that varenicline or bupropion actually cause or exacerbate any of these more severe psychiatric illnesses to any greater extent than quitting smoking itself. On the contrary, the evidence from placebo-controlled trials is very clear that both these medicines reduce the severity of nicotine withdrawal symptoms like low mood and irritability.

While I do agree with FDAs advice that patients using these medicines should be made aware of potential mood and behavior changes and monitored closely, I would extend that advice to anyone attempting to quit smoking, with or without medication.

Labels: bupropion, Chantix, Chantrix, jonathan foulds, nicotine withdrawal, smoking cessation, varenicline, Zyban

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FDA: Boxed Warning on Serious Mental Health Events to be Required for Chantix and Zyban

On the first of July, 2009 the U.S. Food and Drug Administration issued additional information for healthcare professionals and announced that additional warnings will be required on the boxes of smoking cessation aids varenicline (Chantix in U.S.) and bupropion (Zyban, and generics in U.S.) and for the use of bupropion as an antidepressant (Wellbutrin and generics in the U.S.). The advisory is copied in full below and the link is provided. It highlights the risk of serious neuropsychiatric symptoms in patients using these products. These symptoms include changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide.

I’ll give my comments on this in my next posting.

Link to FDA advisory (cut and paste into your browser if link not active):

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm170100.htm


"Information for Healthcare Professionals: Varenicline (marketed as Chantix) and Bupropion (marketed as Zyban, Wellbutrin, and generics)

FDA ALERT [7/1/2009]: 
FDA has required the manufacturers of the smoking cessation aids varenicline (Chantix) and bupropion (Zyban and generics) to add new Boxed Warnings and develop patient Medication Guides highlighting the risk of serious neuropsychiatric symptoms in patients using these products. These symptoms include changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide. The same changes to the prescribing information and Medication Guide for patients will also be required for bupropion products (Wellbutrin and generics)that are indicated for the treatment of depression and seasonal affective disorder.

The added warnings are based on the continued review of postmarketing adverse event reports for varenicline and bupropion received by the FDA. These reports included those with a temporal relationship between the use of varenicline or bupropion and suicidal events and the occurrence of suicidal ideation and suicidal behavior in patients with no history of psychiatric disease. Some of these cases may have been confounded by symptoms typically seen in people who have stopped smoking and are experiencing withdrawal from nicotine.

Healthcare professionals should advise patients to stop taking varenicline or bupropion and contact a healthcare provider immediately if they experience agitation, depressed mood, and any changes in behavior that are not typical of nicotine withdrawal, or if they experience suicidal thoughts or behavior. If varenicline or bupropion is stopped due to neuropsychiatric symptoms, patients should be monitored until the symptoms resolve.

Family members and caregivers should also be alerted to the potential for changes in mood or behavior and contact the health care provider if they observe these changes in the person taking varenicline or buporpion. Varenicline and bupropion are effective smoking cessation aids. The possible risks of serious adverse events occurring while using varenicline or bupropion should always be weighed against the significant health benefits of quitting smoking. The health benefits of quitting smoking include a reduction in the chance of developing lung disease, heart disease, or cancer. 
 
This information reflects FDA’s current analysis of data available to FDA concerning these drugs. FDA is not advising practitioners to discontinue prescribing these products. FDA intends to update this sheet when additional information or analyses become available.
To report any unexpected adverse or serious events associated with the use of these drugs, please contact the FDA MedWatch program using the information at the bottom of the page.

FDA last informed healthcare professionals and patients of the addition of suicidal ideation, attempted and completed suicide, changes in behavior, agitation, and depressed mood in the WARNINGS and PRECAUTIONS sections of the varenicline prescribing information and patient Medication Guide on May 16, 2008. Varenicline (marketed as Chantix) Information FDA is now requiring the addition of this information to the BOXED WARNING and to the Medication Guides for patients who are prescribed varenicline and bupropion under the authorities provided in the Food and Drug Administration Amendments Act (FDAAA).

Recommendations and Considerations for Healthcare Professionals
It is important to discuss the possibility of serious neuropsychiatric symptoms in the context of the benefits of quitting smoking with patients before prescribing these medications. Varenicline and bupropion are both effective smoking cessation aids and the health benefits of smoking cessation are immediate and substantial.
Healthcare professional should monitor all patients taking varenicline and bupropion for serious neuropsychiatric symptoms. These symptoms include changes in behavior, hostility, agitation, depressed mood, suicidal ideation, suicidal behavior and attempted suicide. These symptoms have occurred in patients without pre-existing psychiatric illness and have worsened in some patients with pre-existing psychiatric illness. In most cases, neuropsychiatric symptoms developed during treatment with varenicline or bupropion but in others, symptoms developed after stopping drug treatment.
Patients should be informed that it is not unusual to have symptoms such as irritability, feeling anxious, depressed mood and trouble sleeping when they are withdrawing from nicotine, independent of whether they are taking varenicline or bupropion.
Patients with serious psychiatric illness such as schizophrenia, bipolar disorder, and major depressive disorder, may experience worsening of their pre-existing psychiatric illness while taking varenicline or bupropion.
Patients who discontinue treatment because of neuropsychiatric events should continue to be monitored until symptoms resolve. Although symptoms resolved after treatment was stopped in many cases, there were also some cases where the symptoms persisted.

Information for healthcare professionals to discuss with patients, family members, and caregivers:
Quitting smoking can decrease the chances of lung and heart disease and getting cancer. These important health benefits should be weighed against the small, but real, risk of serious adverse events with use of varenicline or bupropion.
Worsening or recurrence of psychiatric illness. Patients should be told that some patients taking varenicline or bupropion have experienced worsening of their psychiatric illness, even when the illness was under control and some patients have experienced a recurrence of a previous psychiatric illness when taking these drugs for smoking cessation.
Unusual changes in mood and behavior. Patients should be instructed to contact their healthcare provider immediately if they observe or develop thoughts about suicide or attempting suicide, feel agitated, aggressive or violent and other unusual changes in mood or behavior.
Some symptoms are to be expected when quitting smoking. Patients should be told that it is not unusual to have symptoms such as irritability, feeling anxious, depressed mood and trouble sleeping when they are withdrawing from nicotine, independent of whether they are taking varenicline or bupropion and that vivid, unusual, or strange dreams may occur while taking Chantix and are not a cause for alarm.
Discuss other methods of quitting smoking if it is decided that varenicline or bupropion are not the best treatment option
Background Information and Data
FDA first informed the public about the possibility of serious neuropsychiatric symptoms with varenicline in the November 20, 2007 FDA Early Communication About an Ongoing Safety Review. A complete history of related communications on varenicline and bupropion can be found at: Varenicline (marketed as Chantix) Information Since that time, information about serious neuropsychiatric symptoms in patients taking varenicline has been added to the POST-MARKETING EXPERIENCE section of the prescribing information.
As FDA received additional information the suggestion of a possible association between both varenicline and bupropion (which was evaluated as a comparator to varenicline) and serious neuropsychiatric symptoms, in both patients with and those without previous history of psychiatric illness, became more evident as its review progressed. As a result, FDA has required the manufacturers of the smoking cessation products varenicline, and bupropion to add information regarding neuropsychiatric symptoms to the Boxed Warning, and Warnings sections of the varenicline and bupropion prescribing information and update the Medication Guides for patients so that healthcare professionals and patients can be more alert to these issues.

A summary of the data from FDA’s review of varenicline and bupropion were published in FDA Drug Safety Newsletter, Volume 2, Number 1, 2009. This analysis was for all reports received by FDA from the time of marketing approval to November 2007. Access to the article is provided in the link below. FDA has continued to receive reports of neuropsychiatric events in association with use of varenicline and bupropion since the data cut off date for the analysis presented in the Drug Safety Newsletter analysis.
 FDA Drug Safety Newsletter Volume 2, Number 1, 2009 - PDF."

Labels: bupropion, champix, Chantix, Chantrix, jonathan foulds, smoking cessation, varenicline, Zyban

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Combining varenicline and bupropion

I recently received the following comment on my April/15/2007 post:
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

“I have been searching the web and have wondered if anyone knows if you can take both wellbutrin and Chantix at the same time. I have tried Chantix before and I had many of the crazy adverse side effects. It was the one way that I actually stopped for more than a week. I relapsed after 1 year of being smoke free. I have to quit this stuff it is killing me! I am hoping that I can take both of the medications to offset the moodiness I experienced last time. Thanks for your help!”

This is actually a very good question. Varenicline (Chantix) partly works by blocking certain nicotine receptors in the brain. That mechanism makes us doubt the rationale for combining varenicline with nicotine replacement therapy (NT), as varenicline should also block the effects of the NRT. But bupropion, while possibly affecting nicotine receptors, is believed to work via additional mechanisms (e.g. slowing the reuptake of dopamine). So it makes sense to consider whether there may be an added effect of combining those medicines.

Fortunately, the first study of this kind of treatment was very recently published. The study was published in the journal, Nicotine & Tobacco Research” by Dr John Ebbert and colleagues at the Mayo Clinic, in Rochester MN. The treated 38 smokers with the usual dose of varenicline, plus the usual dose of bupropion (SR: sustained release) for 12 weeks. The study was “open label” meaning that there was no comparison or “placbo” treatment and everyone knew what treatment was being provided. All the smokers were also provided with behavioral therapy. After around 12 weeks of treatment, 71% were not smoking (confrmed by a low exhaled carbon-monoxide measure), and at 6 months (i.e. 3 months without any medication) 58% were not smoking.

The most common side effects were those that have already been reported with these medicines. For example, 26% reported sleep disturbance (common with bupropion) and 24% reported nausea (common with varenicline). No increase in depressive symptoms was observed, and no suicidal thoughts were reported. The authors concluded that combination therapy with varenicline and bupropion SR may be effective for increasing smoking abstinence rates above that observed with a single medicine.

Although this study was small, and it is likely that the participants were very highly motivated and received more intensive treatment than is typically available, I agree that these results are quite promising. It is extremely unusual for any smoking cessation study to report a 6-month quit rate above 50%. So this appears to suggest that there may be some additive effects from combining these two medicines that are each effective on their own.

So what should readers who are interested in such a combined treatment do? It is important to note that this is just the first relatively small study, and so overall there is very little experience with this combination. Many doctors may quite reasonably prefer not to take any chances by prescribing a combined treatment before its efficacy and safety have been adequately studied. If you are able to see a doctor who is experienced in using these medicines, and willing to prescribe them together, I would suggest that you remain in regular contact with that prescriber throughout your quit attempt. I would also suggest that you should access some regular behavioral support or counseling (as was provided to the study participants). Hopefully within a year or two we will have more information on the combined use of these two smoking cessation medicines.

Reference
Varenicline and bupropion sustained-release combination therapy for smoking cessation. Ebbert JO, Croghan IT, Sood A, Schroeder DR, Hays JT, Hurt RD.Nicotine Tob Res. 2009 Feb 25.

Labels: bupropion, combination, John Ebbert, jonathan foulds, Nicotine Replacement, smoking cessation, varenicline

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Chantix side effects

Varenicline (AKA Chantix) is a prescription-only smoking cessation medicine that has now been on the market for a couple of years. While studies have shown it to be safe and effective, post marketing surveillance (ultimately via reports by users) have raised concerns that some people may experience severe neuropsychiatric side effects as a result of taking the medicine. In particular, there has been a concern that that people with a psychiatric history (most of whom were excluded from the initial studies) may be at risk if neuropsychiatric symptoms such as depressed mood, agitation, lapses in concentration and suicidal thinking.

There have been relatively few studies of Chantix that included people with a mental illness, so that remains a concern. But last month a new study was published which examined side effects among Chantix users with and without a lifetime history of depression. The study, by Dr Jennifer McClure (Group Health Center for Health Studies, Seattle) and colleagues, compared the rates of side effects among people with (n=661), and people without a history of depression (516) who used Chantix to try to quit smoking while receiving phone and/or internet counseling. The study excluded people suffering from schizophrenia, bipolar disorder, and a few other illnesses. All participants received a telephone interview before starting treatment and 21 days and 3 months after their target quit date (i.e. approx 4 weeks and 13 week s after starting taking Chantix).

The first main finding was that, overall, ratings of symptoms such as depression or stress actually declined after the participants started taking Chantix (and tried to quit smoking), both for those with and without a history of depression. However, smokers with a history of depression felt more tense, irritable, depressed, and confused than those without a history of depression, 21 days after their target quit date (as they did at baseleine), and people with a history of depression who reported depressed symptoms were more likely to report severe depression than those without such a history at 21-day follow-up.

When examining actual change of mood, as compared with baseline, the majority of both groups mood improved after starting Chantix, but 10% of those with a history of depression had a significant worsening, as did 8% with no history of depression. Unfortunately this study was not able to compare these frequencies with people quitting smoking while taking placebo, but earlier placebo-controlled trials have not found a higher rate of mood worsening in Chantix users: quite the opposite.

One other thing worth noting is that both groups had very impressive quit rates, that were actually very slightly higher among those with a history of depression (45%) than those without: (42%) at 3 month follow-up.

So what does all this mean? The study authors interpreted the findings as suggesting that Chantix could be a particularly appealing treatment option for those smokers with a history of depression. Although such smokers are more likely to report common Chantix side effects and nicotine withdrawal symptoms, they had equally high quit rates without clear evidence of a worsening of mood.

So overall these results are somewhat reassuring, and suggest that perhaps we don’t need to be particularly cautious about Chantix use in those with a depression history. However, clinicians, patients and their families and colleagues should continue to monitor patients who are trying to quit smoking, and alert a clinician if a severe worsening of any symptoms appears to be occurring.

Here’s a link to a summary of the study:
http://www.ncbi.nlm.nih.gov/pubmed/19238488?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Here are links to a couple of previous blog posts on Chantix and its side effects, including comments by many people who either did or did not experience side effects:
http://www.healthline.com/blogs/smoking_cessation/2007/04/chantix-how-does-this-new-quit-smoking.html
http://www.healthline.com/blogs/smoking_cessation/2007/09/does-chantix-cause-mental-health.html

Note: I have done consulting and other paid work for Pfizer, the manufacturer of Chantix, as well as for the manufacturers of other smoking cessation products. See disclosure statement on my homepage at healthline.com.

Labels: champix, Chantix, Jennifer Mcclure, jonathan foulds, side effects, smoking cessation, varenicline

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Suicidal thinking while taking varenicline or bupropion

There has been considerable discussion, including on this blog, about the potential for the latest smoking cessation medicine, varenicline (Chantix) to cause severe depression and suicidal thinking. The Food and Drug Administration issued additional warnings on the labeling for Chantix, including advice to monitor for “neuropsychiatric symptoms”.

Some additional data on this issue was recently published in the FDA Drug Safety Newsletter and is worth reading (link below). The report summarizes cases reported to FDA describing suicidal thinking and behavior in connection with bupropion and varenicline use from the date of each compound’s approval (from approval of the smoking cessation indication for bupropion) to November 27, 2007.

FDA identified 153 reports of suicidal adverse events for varenicline (suicidal thinking-116, suicide-37) and 75 reports for bupropion (suicidal thinking-46, suicide-29). These cases likely represent a fraction of those that occurred during this time period due to underreporting to FDA’s Adverse Event Reporting System (AERS). The total yearly prescriptions for these medicines is in the millions, so these cases also represent a tiny fraction of total users.

It was reported that for both medicines, the median time to onset of suicidal thoughts was less than two weeks. Now for both these medicines the recommended treatment procedure involves taking the medicine for a week before trying to quit smoking (on day 8). Both of the medicines are recommended to be taken for over 6 weeks (12-24 in the case of varenicline). It is noteworthy that the timing of these cases of suicidal thinking is typically in the first week after trying to quit smoking…i.e. the precise time period when nicotine withdrawal symptoms (depression, irritability, anxiety, poor concentration, insomnia, restlessness etc) are usually at their worst.

Half of the varenicline cases had a prior psychiatric history and 42% were known to be taking other psychiatric medicines at the same time. These proportions may not be much higher than typically occurs in smokers seeking treatment for tobacco dependence.

The outcomes were serious, and included hospitalization and death. The report provides brief description of 4 cases (2 on varenicline and 2 on bupropion). Surprisingly, no mention is made in these case reports of the timing of smoking cessation (if it occurred). This may be because when the event was originally reported, this information was not provided.

It is also surprising that in the whole report there is no discussion of the potential role of smoking cessation and nicotine withdrawal symptoms in precipitating the reported suicidal thoughts and behaviors (rather than the medicines, per se). At the beginning of the report there is a mention that the FDA also examined the association between the use of the nicotine patch and suicidal thinking, but that no clear association was found. Unfortunately no details were provided.

Overall, this report is useful in that it provides more information on some of the characteristics of these events, including their timing relative to the treatment process. It is interesting that FDA is now expressing a concern about these events in relation to bupropion, but appears not to be considering smoking cessation itself as a potential trigger in a very small minority of smokers.
The data in this report was not of the kind that can really clarify whether or not the medicines themselves may have caused these events. So healthcare providers (and consumers) are reminded to closely monitor for neuropsychiatric symptoms (e.g., changes in behavior, agitation, depressed mood, and suicidal thoughts and behavior) while they are using varenicline and bupropion as smoking cessation aids. Healthcare providers (and consumers or their families) should report any cases of suicidal ideation and/or behavior or any other serious adverse events in patients taking these drugs to FDA's MedWatch program at http://www.fda.gov/medwatch.

Id go further and suggest that providers and consumers should monitor for these symptoms during any attempt to quit tobacco use, regardless of whether or not a medicine is being used.

The report itself can be found at:
http://www.fda.gov/CDER/dsn/2009_v2_no1/postmarketing.htm#varenicline_bupropion

Other blog posts on related topics can be found at:
http://www.healthline.com/blogs/smoking_cessation/2007/11/chantix-varenicline-safety-being.html

and: http://www.healthline.com/blogs/smoking_cessation/2009/02/walmart-sells-smoking-cessation.html

Labels: bupropion, Chantix, FDA, jonathan foulds, smoking cessation, suicidal thinking, suicide, varenicline

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Walmart sells smoking cessation medicine for $9.

Last month Walmart announced that it has started selling the prescription-only smoking cessation medicine, bupropion (same drug as brand version, Zyban) at a lower price than any other effective smoking cessation medicine.

The starter pack, consisting of 17 bupropion 150mg extended-release tablets (a 10-day supply), sells for $9, and subsequent 30-day supplies (60 tablets) will cost $27 (less than $7 per week). Bupropion is typically taken as a single 150mg tablet per day for the first 3 days, then two tablets a day for the next 4 days. The smoker is advised to quit smoking completely on day 8, and continue on two tablets a day for approximately 8 weeks thereafter .

Currently smokers who don’t have health insurance coverage that includes smoking cessation medicines have to pay prices ranging from around $20 for a small box of generic nicotine gum intended to last a few days, up to around $55 for a 2-week supply of nicotine patches or around $130 for a month supply of varenicline (Chantix).

So the chance to get started on bupropion for an initial outlay of only $9, is much less expensive than other options, as is the continuing cost of around $27 per month. Not everyone can tolerate bupropion’s slightly stimulant initial side effect (including agitation and insomnia), but the initial 10-day supply is designed to take people to 3-days after their target quit date. So the smoker can find out if bupropion is helpful to them without a large initial financial outlay.
Bupropion also has the advantage that it can be combined with nicotine replacement therapy (e.g. nicotine gum) to obtain better results, as discussed in a prior blog posting: http://www.healthline.com/blogs/smoking_cessation/2007/09/does-it-help-to-add-nicotine-gum-to.html

You can find full details of the outcomes of smoking cessation treatment with bupropionas described in the New England Journal of Medicine at: http://content.nejm.org/cgi/content/abstract/340/9/685

You can find details of the Walmart announcement at: http://walmartstores.com/FactsNews/NewsRoom/8904.aspx

Labels: bupropion, Chantix, cigarette, jonathan foulds, nicotine gum, NRT, smoking cessation, varenicline

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How to Quit Smoking With Varenicline (Chantix).

A friend recently told me that her mom was about to try to quit smoking by using Chantix. She had heard some scary things about the drug and wanted some simple advice on how to use it effectively and safely, and also on what she could do to help.

Of course the most important thing to do in that situation is to tell your mom you love her and that you are really pleased she is trying to quit smoking. Support and encouragement from a family member can be a great help, particularly when there has been a history of unsuccessful quit attempts and the person may be discouraged by fear of failing again.

The next obvious thing to say is that it is important to follow the advice of the doctor who prescribed the medicine, and to thoroughly read the labeling and instructions for use that come with the medicine. I say this because the fact is that most of us forget the detailed instructions given by our doctor, within five minutes of leaving the appointment. Similarly, many of us don’t read the labeling properly at all (me included). But stopping smoking is a life-saving intervention and these medicines are not without their risks and side effects so it is worth taking the time.
One problem with Chantix is that it causes some side effects, with nausea being the most common (around 30% of users experience some nausea). The medicine should be taken for 7 days prior to the “Quit Date” (day 8 of the medicine), on an increasing dose (0.5mg once per day on days 1-3, the 0.5mg twice per day days 4-7) until starting the full dose (1mg twice per day) on day 8. One important tip is to take the tablet with a large glass of water, after eating. This will tend to reduce the severity of nausea. If the nausea is too much (happens in less than 5% of patients) then it is worth going back to the doctor, who can prescribe a reduced dose of 0.5mg tablets that can be supplied in bottled form at the pharmacy. This dose has much less severe side effects and is almost as effective at reducing cigarette cravings and withdrawal symptoms.
Chantix works via two separate mechanisms. Firstly it stimulates nicotine receptors in the brain in a way that reduces nicotine withdrawal symptoms and cravings. Secondly it blocks those receptors so that the nicotine from a cigarette cannot have its usual satisfying effect. Many patients find that though they continue smoking during the first 7 days of therapy, those cigarettes become less satisfying. Similarly a “lapse” cigarette after day 7 will likely also be less satisfying and less likely to lead to a full blown relapse. Although it is important to aim for complete abstinence from smoking (i.e. not a single puff) from the target quit day, slips needn’t be viewed as a complete disaster or a reason to give up. With Chantix these slips may actually serve to teach the brain that it will no longer get satisfaction from smoking (at least while taking Chantix).

There have been some other widely publicized side effects of Chantix, including some that may not be directly caused by the drug. It is clear, for example that Chantix (like the 24-hour nicotine patch) stimulates vivid dreams, or at least causes more of these to be remembered on wakening. This can be troubling if the dreams are nightmares, although they are frequently not nightmares. There have also been reports of other “neuropsychiatric side effects” in people taking Chantix. These have included agitation, depression and suicidal thoughts. It is not clear that Chantix causes any of these symptoms, but it is recommended that patients be monitored for this kind of adverse reaction while taking Chantix. So family members should keep an eye on the person trying to quit, and check how they are feeling. If there are any signs of very troubling thoughts or behavior, then the doctor should be called without hesitation. Of course some moodiness is absolutely normal on quitting smoking, even while taking Chantix. It is wise to check back with the prescribing doctor within a week of the target quit date to let him/her know about progress and any side-effects.

Although Chantix comes with its own online/telephone support plan (“Get Quit), I think it is wise to obtain as much additional support as possible. Ideally this would involve attending a local specialist smoking cessation service and being assessed by a trained counselor. If such a service is not available locally, it is certainly worth phoning the national telephone “Quitline” at:
1-800 QUITNOW (1-800 -784-8669)

The service provided may vary by state, but usually includes an option for telephone counseling.
In addition, I would recommend getting additional support from some of the excellent quit smoking websites that are available. Two of the best are:
www.quitnet.com and www.becomeanex.org

Sometimes when taking a medicine to quit smoking it is easy to build up expectations that it will be a wondercure, and then be disappointed when the cravings still occur and it gets hard. So the most important thing is to continue to be supportive when the going gets tough. Helping the would-be quitter to keep trying even when it is tough, and even after some failed attempts , is key. Many people have a few slips along the way and may even go back to full-blown smoking for a while, but if they set a new quit date, and keep taking the medicine, they will still stand a good chance of successfully quitting.

Sometimes people stop taking Chantix after a month or so because they feel it has worked and they no longer need it. However, the evidence suggests that taking the full course will likely produce better outcomes, and after 12 weeks on the medicine the doctor can prescribe for another 12 weeks to help prevent relapse. In addition to taking the medicine, making sure no tobacco is left around the house, making sure every success is celebrated and continuing to support the quit attempt beyond the initial few weeks, will all help prevent relapse to smoking.
Sometimes people taking Chantix are pleased that they can cut down their smoking without too much effort. But I think its critical to keep going until you get to zero cigarettes per day, and stay with it. To do that you need to get rid of all the cigarettes and be clear that the aim of the game is quitting, not cutting down. Unfortunately most people find that when they have cut down for a while they increase again when a period of stress comes along.

So the main advice is to keep trying, focusing on not taking a single puff of tobacco, and taking it a day at a time.

Labels: Chantix, jonathan foulds, side effects, stopping smoking, varenicline

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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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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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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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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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Two new studies of Chantix (varenicline)

Two new trials of the smoking cessation medicine varenicline (Chantix) were published this past weekend. One reported the results in 515 nicotine-dependent Japanese smokers (mainly men) and the other reported the results in 250 Korean and Taiwanese smokers.

The Japanese study compared the outcomes across various doses of varenicline, with participants taking the pills for 12 weeks, and then being followed up for a further 40 weeks off drug. As in previous studies, the 1mg dose (twice daily) achieved slightly higher quit rates than lower doses, albeit with higher reported side-effects. The 1mg dose achieved abstinence rates of 65% at 12 weeks, as compared with 40% among those using placebo pills. At one year follow up, 35% of those who were given 1mg pills for the first 12 weeks remained abstinent, compared with 23% of those who had taken placebo pills. So this study in Japan confirmed the safety and efficacy of Chantix, but the “effect size” – the degree to which the drug performed better than placebo, was not quite as impressive as previous studies. This was partly because a relatively large proportion of Japanese smokers in this study succeeded in quitting while using placebo pills.

Another study based in Korea and Taiwan directly compared 12 weeks of 1mg varenicline with 12 weeks of placebo in 250 smokers (mainly men). After 12 weeks, 60% of those using varenicline were not smoking, compared with 32% of those using placebo pills. After 24 weeks (i.e. another 12 weeks “off drug”) the quit rate was 47% among those who had used varenicline, versus 22% among those who had used placebo. As in previous studies, those taking varenicline were more likely to report some nausea, constipation and abnormal dreams, but these were generally mild in nature. Also like prior studies, those on Chantix were not less likely to report an increased appetite. This is noteworthy as most previous smoking cessation medicines (such as nicotine replacement therapy or bupropion) tend to reduce appetite compared with placebo, and suggests that Chantix works via a slightly different mechanism.

So far, the placebo-controlled trials of varenicline have been remarkably consistent in finding that it approximately doubles quit rates compared with placebo, and that this increased quit rate is maintained even after up to 40 weeks off drug. The early studies suggested that Chantix may result in higher quit rates than other pharmacological treatments for smoking. Whether this ultimately turns out to be the case will require additional studies directly comparing different treatments.

The take-home message for smokers interested in trying to quit is that this new medicine continues to demonstrate that it is safe and effective in increasing smokers’ chances of successfully quitting, with the most frequent side-effect being mild nausea (16-42% of users). The nausea is less marked at lower doses, and also appears less when taking the pill along with food and water. Most people using Chantix are able to continue using it and the initial nausea subsides. Those continuing to take Chantix for the full course (up to 24 weeks) tend to have higher quit rates than those discontinuing early.

Labels: addiction, cessation, Chantix, cigarette smoking, nicotine, tobacco, varenicline

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Chantix and mental illness - what are the facts?

The August issue of the American Journal of Psychiatry included two letters reporting single cases of worsening of symptoms of schizophrenia and mania, while they were taking the new smoking cessation medication, Chantix (varenicline). Links to those case reports can be found below. It was also noticeable that some readers of my previous article on Chantix who were also taking medications for psychiatric problems wrote online comments about unpleasant side effects.
http://www.healthline.com/blogs/smoking_cessation/2007/04/chantix-how-does-this-new-quit-smoking.html

People suffering from major mental illnesses were excluded from the initial placebo-controlled trials of varenicline (Chantix), which showed that it is both safe and effective in helping smokers to quit. It is normal practice to exclude certain categories of patient from trials of new medicines, prior to the drug being approved for sale to the public. Often the reason is that patients with certain diagnoses are more likely to be taking medications that may affect the condition being treated (e.g. antidepressants could theoretically affect smoking cessation, as at least 2 antidepressants are effective for smoking cessation). Sometimes it is partly to protect those considered “at risk”, from taking an unlicensed experimental medicine. What we end up with is that many new medicines have mainly been studied in people who are relatively healthy, apart from having the condition the new medicine is designed to treat. Chantix is like many new drugs in this respect. It is also very common, especially for new medicines that are very widely used, for reports to appear of unusual side-effects occurring in some patients. I’ve published a few such reports myself.

However, it is not until fairly thorough additional placebo-controlled studies have been published in more patient groups, that we can tell with any confidence whether the new drug really does cause problematic side effects in certain patient groups or not. Sometimes such studies are never carried out and in that case we need to rely on the reported experiences of clinicians treating those patient groups over a period of time.

One thing we have to bear in mind is that when a person starts using Chantix, that’s not the only thing that’s changing. That person will also be trying to quit smoking. Quitting smoking itself causes a number of changes, including the increases in nicotine withdrawal symptoms I’ve talked about before (see link below), and also a slowing in metabolism of some medications, that could cause an increase in the blood levels of the drugs contained in those medicines (I’ll discuss this in a future post). So some symptoms may be related to quitting smoking, rather than Chantix per se.

So if I had a relative who smoked and suffered from a mental illness (like schizophrenia, bipolar disorder or depression) and was taking medicine for that illness but wanted help to quit smoking, what would I suggest?

As with all the people I see who want to quit smoking, I’d describe all the available forms of help, including counseling, internet support and medicines. I’d recommend that they use these. With regards to medicines, I’d point out one advantage of nicotine replacement therapy, which is that it does not involve taking a “new” drug, - as they have been taking nicotine in a much more harmful form every day, for years. When discussing Chantix I’d point out that it had not been studied in many people with a serious mental health problem, and so it would be particularly important to discuss that option with their doctor and to allow the doctor to monitor their progress on that medicine fairly closely if the doctor decided to prescribe it. But if my family member had already tried nicotine replacement therapy and wanted to try something different, I wouldn’t discourage it. I’ve heard from many clinicians who have treated patients with mental health problems successfully with Chantix, and so I am not convinced yet that there is a markedly increased risk of adverse events caused by Chantix in such patients.

It would be helpful to hear peoples’ experiences of using Chantix, particularly if you have also had a mental health problem. If you feel that any medicine has caused a harmful effect, then you should tell your doctor, and particularly in the case of a new medicine, it may be appropriate to report this to the FDA. For further information on that procedure, visit: http://www.fda.gov/medwatch/

Here are the links to the recent case reports:
http://ajp.psychiatryonline.org/cgi/content/full/164/8/1269
http://ajp.psychiatryonline.org/cgi/content/full/164/8/1269-a

Here is the link to my previous article on nicotine withdrawal:http://www.healthline.com/blogs/smoking_cessation/2007/03/what-is-nicotine-withdrawal-syndrome.html

Labels: Chantix, mental illness, quit smoking cessation tobacco advice cigarettes, Smoking, tobacco, varenicline

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