One of the most preventable causes of morbidity and mortality in the United States is cigarette smoking. It was estimated that smoking-related disease would lead to more than 400,000 deaths in the United States in 2001. Smoking cessation before 50 years of age has been shown to reduce all causes of death by 50 percent in the following 16 years. Smoking cessation can increase life expectancy even in persons who stop smoking after 65 years of age. However, only 2.5 percent of all smokers who attempt cessation remain abstinent for one year. One of the main problems for those attempting to stop smoking is withdrawal from nicotine. Withdrawal from nicotine has been associated with the presence of depressive symptoms. Previous studies have shown that two different antidepressant medications were successful adjuvants in smoking cessation. Da Costa and colleagues evaluated the efficacy and safety of nortriptyline in a smoking cessation program.

The participants in the study had volunteered to participate in a smokers' support group. Inclusion criteria included the following: 18 to 65 years of age; smoked at least 15 cigarettes per day for the past year; were not depressed according to the Beck questionnaire; and had no recent psychiatric treatment history. During the initial interview, each participant's dependence on nicotine was measured using the Fagerström questionnaire. A total of 144 participants were randomized to receive 75 mg per day of nortriptyline (68 patients) or placebo (76 patients) during the six-week study period. All patients attended a smoking behavioral group for five weeks. The outcome measures included the rate of success, complications, adherence to the regimen, and factors of pretreatment prognosis.

The treatment and placebo groups were balanced with regard to patient characteristics. Patients who received nortriptyline had a smoking cessation rate of 56 percent compared with a cessation rate of 23 percent in those receiving placebo. When prognosis factors were assessed to determine predictors of successful smoking cessation, only the use of nortriptyline and a low Fagerström score (less than 7) suggesting low nicotine dependency predicted success. There were no significant adverse effects in the nortriptyline group. At six months from baseline, the patients receiving nortriptyline had a cessation rate of 20.6 percent compared with a 5.3 percent cessation rate among those receiving placebo.

The authors conclude that nortriptyline is an effective and well-tolerated medication for the treatment of smoking addiction. The success rate for nortriptyline was similar to rates reported for bupropion treatment. Nortrip-tyline was more effective in patients with a higher nicotine dependence score.

editor's note: Smoking cessation is one of the most challenging aspects of patient care. Despite vast knowledge of the risk of smoking and the benefits of cessation, many patients continue to smoke, and many who attempt to stop, fail. The use of adjuvant therapy for smoking cessation has provided better response rates than an attempt to quit without such help. The study by da Costa and colleagues provides physicians with another adjuvant medication. The advantage of nortriptyline is that it comes in a generic form that substantially reduces the cost to patients, eliminating one of the more common problems facing those who wish to stop smoking. This is particularly true because most insurance companies do not cover smoking cessation medications.—k.e.m.