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In the era before the Surgeon General’s report established tobacco smoking as carcinogenic and bad for your heart, quaint cigarette ads played on women’s fears of obesity by urging them to "reach for a Lucky Strike instead of a chocolate."
But the results of a study in the October 23 New England Journal of Medicine suggest that today’s smokers might instead reach for 300 mg of the antidepressant bupropion instead of a cigarette. The study found that bupropion, particularly at a dose of 300 mg daily, helped smokers quit while minimizing the weight gain that so often bedevils those struggling to give up the noxious weed.
The study by internist Richard Hurt, M.D., and colleagues at the Nicotine Research Center of the Mayo Clinic in Rochester, Minn., employed a sustained release form of the drug. Researchers administered daily doses of either 100 mg, 150 mg, or 300 mg bupropion or a placebo in a seven-week, double-blind trial of 615 men and women at three sites nationwide with follow-up through one year.
Approximately 44 percent of those on the 300 mg daily dose had successfully quit smoking at the end of the seven-week study. This compared with only 19 percent in the placebo group and about 39 percent in the 150 mg group. There was no significant difference between the effect of 100 mg daily and placebo.
At one-year follow-up, approximately 23 percent of both the 300 mg and 150 mg groups were not smoking, compared with about 20 percent of the 100 mg group and 12 percent of the placebo group.
Bupropion treatment had no effect on depression scores as measured by the Beck Depression Inventory. The study design excluded smokers with current depression, but not those with a history of major depression.
Typical weight gain associated with successfully stopping smoking is about 6.5 pounds to 8 pounds. In this study, those on the 300 mg daily dose gained only 3.3 pounds, or about half as much as the placebo group, which gained 6.4 pounds.
Concern with weight gain "inhibits many smokers (especially women) from attempting to stop," the authors commented. "A medication effective for smoking cessation that is also capable of minimizing the associated weight gain" offers a major advantage.
The drug’s lack of impact on depression scores suggests that "the mechanism for bupropion’s efficacy [as a smoking deterrent] is unlikely to be through its antidepressant effects," the authors observed.
Although scientists have yet to elucidate the mechanism for bupropion’s efficacy in helping smokers quit, it seems likely that the drug’s impact on dopamine is involved, said Hurt. Dopamine has increasingly been linked to the pleasurable effects of addicting drugs, including nicotine, cocaine, and heroin. Bupropion weakly inhibits neuronal reuptake of dopamine and norepinephrine.
The suspicion that dopamine is involved in smoking has been strengthened by research showing that fluoxetine (Prozac) is ineffective as a smoking deterrent. Fluoxetine affects serotonin but not dopamine.
Partly on the basis of the current study, sustained-release bupropion was recently approved by the Food and Drug Administration as a prescription drug for smoking cessation under the trade name Zyban.
Although the study excluded currently depressed subjects, "there are a lot of connections between depression and smoking," Hurt commented. "I would hope psychiatrists begin to dig into this more and address smoking interventions for their patients. They are seeing an at-risk population, and we need their help and assistance in learning how better to treat them."
Whether bupropion can be useful to patients already taking another antidepressant for depression is a good question, said Hurt. Patients who are already on a psychotropic and are interested in trying bupropion for smoking cessation should talk to a psychiatrist, he advised.
"If somebody’s depressed, that’s not a good time to quit smoking," said John Hughes, M.D., chair of APA’s Task Force on Nicotine Dependence. "We try to get [patients] undepressed before they quit smoking."
The psychiatrist should "choose the antidepressant that he thinks will work best for the depression" and worry later about the smoking, Hughes added.
Other antidepressants, including nortriptyline and a European monoamine oxidase inhibitor called moclobemide, also have been used to help people stop smoking, said Hughes. It is not clear that bupropion is a more effective smoking deterrent than these other drugs.
"The main thrust that people need to understand is that [bupropion] is apparently not working as an antidepressant" but through some other mechanism, said Hughes.
While bupropion and other pharmacological interventions, including nicotine delivery systems such as patches and gum, will undoubtedly help millions quit, psychiatrists are likely to end up with the most recalcitrant smokers, according to Hughes.
Psychiatry is "undergoing a huge selection bias" in that people who do not have severe nicotine dependence and psychiatric comorbidity are quitting on their own or through "social pressure or use of over-the-counter nicotine gum or patch," he said.
A decade from now those who are still smoking will be the most addicted and hence hardest to help quit, Hughes said.
Surveys suggest that as many as 90 percent of psychiatric patients are not motivated to quit smoking, said Hughes. But it is nonetheless incumbent on the psychiatrist to raise the issue, he added. Failure to do so undermines whatever motivation to quit that the patient may have, he said.