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The authors review recent literature that has demonstrated an association between cigarette smoking behavior and major depression. Persons with major depression are more likely to smoke and to have difficulty when they try to stop. When they manage to succeed in stopping, such persons are at increased risk of experiencing mild to severe states of depression, including full blown major depression. The period of vulnerability to a new depressive episode appears to vary from a few weeks to several months after cessation. This knowledge suggests a relationship between smoking and depression that is complex, pernicious, and potentially life-long. It is recommended that cessation treatments incorporate screening procedures that will identify those patients with a propensity to depression and monitor the emergence of postcessation depression, particularly in those with a history of depression.

These results provide, at best, mild promise for naltrexone as a smoking cessation drug and provide another instance of a differential response to nicotine dependence treatment according to gender and depression history.

Measures of addiction and major depression predict treatment failure. Together they are stronger predictors of outcome than drug. Clonidine is a limited aid in cessation, and drug effects come primarily from women at high risk for treatment failure. An increased risk for psychiatric complications after smoking cessation was apparent among smokers with histories of major depression, particularly bipolar disease.

Seventy-one heavy smokers who had failed in previous attempts to stop smoking participated in a randomized clinical trial to test the efficacy of clonidine as an aid in smoking cessation. The success rate in clonidine-treated subjects (verified by serum cotinine concentration) was more than twice that in the placebo-treated subjects. When the data were stratified by gender, a strong effect present in women was not apparent in men. After six months, cessation rates remained significantly higher among smokers treated with clonidine than those receiving placebo. The data also revealed an unexpectedly high prevalence (61%) of a history of major depression in this sample and a significant negative effect of such a history on cessation regardless of treatment. These findings, highly suggestive of an important role of clonidine in smoking cessation, warrant further studies to establish the long-term (greater than or equal to 12 months) efficacy of this drug and to replicate the association between nicotine dependence and depression.

Sertraline did not add to the efficacy of an intensive individual counseling program in a double-blind, placebo-controlled study. However, given that the end-of-treatment abstinence rate for the placebo group was much higher than expected, it is unclear whether a ceiling effect of the high level of psychological intervention received by all subjects prevented an adequate test of sertraline.

Continued patient care beyond the 2-4-week period associated with the nicotine withdrawal syndrome is indicated when abstinence is attempted by smokers with prior major depression.