Smoking Cessation: What Works Best?

In the May issue of JAMA Psychiatry (formerly Archives of General Psychiatry)  Paul Cinciripini and colleagues from the University of Texas in Houston report on their interesting study on pharmacologically-supported smoking cessation (Cinciripini et al., JAMA Psychiatry 2013; 70: 522-533). Still about 45 million Americans smoke, 50% of which undertake a serious attempt a year to stop smoking, but only 6% of them manage to remain abstinent for at least six months. There is therefore a great need for effective therapeutic interventions.

Cinciripini et al. included 294 nicotine-dependent subjects in their randomized, double-blind study. They were treated for 12 weeks with either varenicline (a highly selective partial agonist at α4β2-nicotinic acetylcholine receptors, n = 86) or bupropion (a norepinephrine/dopamine reuptake inhibitor, which may also exert antagonistic effects on α4β2 nicotinic acetylcholine receptors, n = 102) or placebo (n = 106). Over the entire period, all participants received behavioral therapy-oriented counseling (six personal sessions of 30 minutes, four telephone consultations of 15 minutes duration, total 240 minutes). Main outcomes measures were the abstinence rates at the time of termination of pharmacological treatment (using different definitions of prolonged and continuous abstinence), and various parameters of nicotine withdrawal such as depression or irritability.

Pharmacotherapy was started 12-19 days before terminating the nicotine consumption. Varenicline was administered in the first three days in a dose of 0.5 mg, on days 4-7 0.5 mg were given twice daily, the target dose of 1 mg twice/day was achieved on day 8. Bupropion was administered on days 1-3 in a dose of 150 mg, with the target dose of 150 mg twice daily to be administered on day 4.

Both active treatments were significantly more effective than placebo. At all time points examined, i.e. up to six months after cessation of smoking, varenicline was significantly more effective than placebo. Depending on the definition of abstinence, six months after cessation of smoking 14-18% of subjects treated with placebo were abstinent, while 28-38% were abstinent with treatment with varenicline. Bupropion was significantly more effective than placebo, however, abstinence rates were no longer statistically significantly lower after six months (with abstinence rates under bupropion at 23-27%). Depending on the time point after smoking cessation, abstinence rates were between 6% and 12% higher with varenicline than with bupropion, but these differences were not statistically significant.

Subjects who received placebo and who maintained their abstinence during treatment had lower values ​​for sadness, anxiety and negative affect. Subjects treated with varenicline who had a relapse during treatment, reported a lower rewarding effect of smoking. While in subjects who received placebo or bupropion, depression scores were lower in abstainers than in subjects who had a relapse, this was not the case for subjects who received varenicline. In the latter, relapsing subjects had generally lower depression scores. Both active medications were affecting concentration better than placebo. Neuropsychiatric adverse effects were not observed. In subjects treated with varenicline, nausea occurred more frequently than in the other two groups, insomnia was more common in subjects treated with bupropion.

Overall, the results of this study support findings from Phase III studies, according to which varenicline is the most effective agent for the pharmacological support of smoking cessation. Various symptoms of nicotine withdrawal are effectively suppressed. At least in subjects who have no neuropsychiatric disorders, varenicline does not seem to lead to adverse neuropsychiatric effects.

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