A new 'wonder drug' designed to help people stop smoking is under investigation by the US Food and Drug Admin-istration (FDA) following reports that it may be responsible for suicidal, aggressive and erratic behaviours.
Varenicline-Chantix in the US and Champix in Britain-is a partial agon-ist of the a4b2 nicotinic acetylcholine receptors (nAChRs) that are linked to the addictive effects of nicotine. The drug is said to relieve the cravings and withdrawal symptoms associated with stopping smoking, as well as removing the satisfaction gained from the habit. In early trials, when taken twice a day for 12 weeks, it successfully helped 44 per cent of smokers to quit, compared with 17.7 per cent of those taking a placebo and 29.5 per cent of those taking bupropion, its antidepressant rival (JAMA, 2006; 296: 47-55).
However, in the wake of the suicide of a patient who had used the drug, patients in the US taking varenicline are now being advised to contact their doctor as soon as they experience mood changes or feel depressed. Doc-tors are also being asked to keep a close eye on these patients.
In an 'early communication' regarding varenicline, the FDA said it's too soon to say whether there is a causal rela-tionship between the drug and suicide. Nevertheless, the agency is currently reviewing all available information on its adverse events, including the postmarketing data from the drug's manufacturer Pfizer, and reports from the media and on the Internet.
A preliminary assessment reveals that many of the cases reflect a new onset of a depressed mood, suicidal thoughts, and changes in emotion and behaviour within days to weeks of starting varenicline treatment.
The role of the drug in these cases is not clear, says the FDA, because smoking cessation with or without drugs is associated with nicotine-withdrawal symptoms, and can also exacerbate any underlying psychiatric illness. Yet, two recently reported case studies suggest that varenicline itself can worsen the symptoms of schizo-phrenia and bipolar disorder (Am J Psychiatry, 2007; 164: 1269-70).
Furthermore, according to the FDA's data, not all of the patients displaying mood and/or behavioural changes had any preexisting psychiatric illness, and not all of them had stopped smoking, thus eliminating the possibility of withdrawal symptoms.
The UK's popular press recently publicized the case of Omer Jama, a television editor who slashed his wrists just four weeks after starting a course of Champix and died. According to his family, Mr Jama had no history of depression and "was never the sort of person you would see feeling sorry for himself".
Between 15,000 and 20,000 people in the UK have used Champix since it was launched in December 2006. So far, the UK's drugs monitoring body, the Medicines and Healthcare Prod-ucts Regulatory Agency (MHRA), has received 839 reports of adverse reactions to the drug, including 46 reports of depression and 16 reportsof patients who experienced suicidal thoughts.
A spokesman for the MHRA says that, although there have been no reported suicides, it is nonetheless closely monitoring the issue of suicidal tendencies in patients taking Champix.
Other safety concerns
Abnormal behaviour and feelings are not the only safety issues surrounding varenicline. As the FDA and MHRA both point out, the drug can also cause drowsiness and, thus, should not be used when driving or operating mach-inery. Indeed, two patients have been involved in driving accidents while taking varenicline, although whether the drug is to blame is not known.
Moreover, a glance at Pfizer's pres-cribing information for varenicline (see www.pfizer.com) reveals a laundry list of its reported side-effects so far. The most common are nausea, headache and abnormal dreams (see box below) but, rarely, there's also atrial fibrilla-tion (an abnormal heart beat), night-blindness, deafness, convulsions and facial palsy.
Bupropion (Zyban), made by Glaxo-SmithKline, is also linked with serious adverse effects-from insomnia and, if overdosed, tachycardia-an abnormally fast heart rhythm-to seizures and fatal convulsions (Expert Opin Drug Saf, 2002; 1: 303-5; Cochrane Database Syst Rev, 2007; 1: CD000031).
Considering that there are much safer ways to quit smoking, these drugs should not be thought of as 'magic bullets' for smoking cessation.
For alternative ways to kick the habit, see WDDTY vol 18 no 3 (June 2007).
- Abnormal dreams
- Gingivitis (gum disease)
- Chest pain
- Flu-like illness
- Disturbed attention capacity
- Menstrual disorder
- Polyuria (excessive urination)
- Musculoskeletal pain
- Excessive sweating
- Dysgeusia (change in taste