In the midst of the varenicline (Chantix, Pfizer) controversy, perhaps we should just ask the experts who've already studied thousands of patients about their experiences. If this compound can make one into both a Dr Jekyll and Mr Hyde, wouldn't some of these researchers have seen Mr Hyde by now? There have been claims ranging from suicidal ideation to becoming a victim of homicide and include new-onset seizure disorder, depression, and anxiety. We accept that these maladies arise de novo everyday in the US, but if the patient is on no medication, there is no one to sue.

Dr Serena Tonstad

Dr Serena Tonstad is one of the most qualified individuals to assess the current status of varenicline. Formerly of the Ulleval University Hospital, in Oslo, Norway, and now continuing her career at Loma Linda University, CA, where she received her master's in public health nearly three decades ago, she has not only directed a landmark clinical trial on the safety and efficacy of varenicline, but she has also prescribed it to hundreds of private patients and continues to do so.

Prior varenicline studies by Dr Doug Jorenby (University of Wisconsin, Madison) [1] and Dr David Gonzales (Oregon Health and Science University, Portland) [2] of smoking cessation were the first to demonstrate superiority of varenicline over placebo and bupropion (Zyban, GlaxoSmithKline). Jorenby's trial consisted of 1027 patients, in which a 43.9% quit rate on therapy and 23% continued abstention from tobacco in the follow-up period gave researchers the greatest hope for an effective smoking-cessation tool in the history of addiction medicine. Gonzales's trial consisted of 1025 patients, in which 44% of varenicline patients stopped smoking in comparison with 29% on bupropion and 17% with placebo. In the follow-up period in this trial, cessation was maintained in 8.4% of placebo patients, 16% of bupropion patients, and 21% of varenicline patients. Tonstad's trial [3] included 1927 patients, which differed from the others by asking "Do smokers who quit with varenicline do better to avoid relapse by continuing with another 12 weeks of therapy?" The answer was yes. After 40 weeks, 43% of successful quitters who used varenicline were smoke free, whereas 36% of former varenicline users treated with placebo in the follow-up period remained smoke free.

These scientists' access to patient demographics, results, and trial design involving thousands of patients, added to Tonstad's clinical experience, make her well-qualified to speak on the side-effect profile of this medication.

Melissa Walton-Shirley (MWS): Was there any side effect other than extreme nausea that caused you to advise a patient to stop varenicline?

Tonstad: There was just one patient who described it by saying "I am just not feeling myself . . . aggressive." However, she was continuing to smoke. We were not certain if it was the medication or the combination of continuing to smoke while using the medication.

MWS: Is there any psychiatric diagnosis in which you would not prescribe this medication?

Tonstad: I would very carefully weigh the benefits and potential risks. They [psychiatric patients] just cannot manage smoking on their own. I feel confident in prescribing varenicline as long as the follow-up is certain. I would not do it in any patient with uncertain follow-up. The benefits are so large . . . they really need it. In depressed patients, I make sure they are stable, and I might consider decreasing the dose to 1 mg/day.

MWS: What is your opinion regarding the FDA ruling that restricts the use of varenicline in pilots?

Tonstad: I understand the safety of the public must come first. I understand that if there is an accident, they might come back to that. However, there is no known physiologic mechanism to explain the reports of mood swings, depression, suicidal ideation, or other changes in behavior.

However, I do not see the psychiatric population. My clinic is a preventive cardiology clinic. However, I am surprised by the postmarket reporting on this medication. There are some physicians who are reporting these side effects.

MWS: Would you feel more comfortable flying with a pilot who smokes or a pilot who takes varenicline?

Tonstad: I have no problem flying with a pilot who is taking varenicline.

MWS: What measures do you advise to decrease the side-effect profile?

Tonstad: In less than 3% of patients I've prescribed an antiemetic such as Phenergan (promethazine) or Zofran (ondansetron). I also ask them to take it on a full stomach and consider decreasing the dose to 1 mg/day. The dose of 1 mg/day is very effective.

MWS: I note that the side-effect profile of placebo in one trial was 10% and with varenicline it was 12%. Does this indicate that the population of patients who are nicotine addicted are depressed, anxious individuals with mood swings at baseline?

Tonstad: It is possible, and in two months, there will be a poster that will be available that will address some of these issues, but I cannot divulge any information about that poster at this time.

MWS: Have you ever seen a new-onset seizure disorder develop in any patient either in clinical trials or in your clinical experience while prescribing varenicline?

Tonstad: Never.

MWS: Chantix is indicated in patients older than 18 years of age. Is there any circumstance in which you would consider prescribing it in younger patients?

Tonstad: In highly motivated individuals with good follow-up.

MWS: Are you planning trials with greater than six months of therapy?

Tonstad: There are good data that it is effective even at one year.

MWS: What could be any possible mechanism for why the reports of suicidal ideation, homicidal ideation, etc, are just now surfacing?

Tonstad: Perhaps the study populations were completely different from the clinical populations, or perhaps the side effects are manifesting in a time period farther out from therapy than the trials were designed to detect.