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Sharon M. Hall, PhD; Victor I. Reus, MD; Ricardo F. Muñoz, PhD; Karen L. Sees, DO; Gary Humfleet, PhD; Diane T. Hartz, MA; Sydney Frederick, PhD; Elisa Triffleman, MD

Arch Gen Psychiatry. 1998;55:683-690.

Background  A history of major depressive disorder (MDD) predicts failure to quit smoking. We determined the effect of nortriptyline hydrochloride and cognitive-behavioral therapy on smoking treatment outcome in smokers with a history of MDD. The study also addressed the effects of diagnosis and treatment condition on dysphoria after quitting smoking and the effects of dysphoria on abstinence.

Methods  This was a 2 (nortriptyline vs placebo) x 2 (cognitive-behavioral therapy vs control) x 2 (history of MDD vs no history) randomized trial. The participants were 199 cigarette smokers. The outcome measures were biologically verified abstinence from cigarettes at weeks 12, 24, 38, and 64. Mood, withdrawal, and depression were measured at 3, 5, and 8 days after the smoking quit date.

Results  Nortriptyline produced higher abstinence rates than placebo, independent of depression history. Cognitive-behavioral therapy was more effective for participants with a history of depression. Nortriptyline alleviated a negative affect occurring after smoking cessation. Increases in the level of negative affect from baseline to 3 days after the smoking quit date predicted abstinence at later assessments for MDD history–negative smokers. There was also a sex-by-depression history interaction; MDD history–positive women were less likely to be abstinent than MDD history–negative women, but depression history did not predict abstinence for men.

Conclusions  Nortriptyline is a promising adjunct for smoking cessation. Smokers with a history of depression are aided by more intensive psychosocial treatments. Mood and diagnosis interact to predict relapse. Increases in negative affect after quitting smoking are attenuated by nortriptyline.

From the Department of Psychiatry University of California, San Francisco (Drs Hall, Reus, Muñoz, Sees, Humfleet, Frederick, and Triffleman and Ms Hartz); and the San Francisco Veterans Affairs Medical Center Psychiatry Service, San Francisco (Drs Hall, Sees, and Triffleman). Dr Triffleman is now at the Department of Psychiatry, Yale University, New Haven, Conn.

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