A New Use for an Old Drug

Abstract & Commentary

Synopsis: Nortriptyline significantly increased smoking cessation rates compared with placebo.

Source: da Costa CL, et al. Chest. 2002;122:403-408.

This was a straightforward, randomized, prospective, placebo-controlled study. One hundred forty-four patients recruited from a "Smokers’ Support Group" in a cancer hospital in Sao Paulo, Brazil, completed the study. After screening, patients were randomized to receive either Nortriptyline (Pamelor) or placebo daily for 6 weeks. The dose was begun at 1 tablet, and increased to 3 tablets by the end of the study period (75 mg/d of nortriptyline). It is important to note that patients also received weekly group support therapy conducted by a psychiatrist. Smoking cessation was defined as stopping smoking for at least a week at the end of the treatment period. Phone calls 3 months and 6 months after termination of the study were also done to determine continued abstinence rates.

At the end of 6 weeks, 32% of those who received placebo and 68% of those who received nortriptyline reported stopping smoking. At 6 months, 20.6% of the nortriptyline and 5.3% of the placebo group reported continued abstinence. There were no differences in rates of side effects, the most common of which were dry mouth, constipation, and anxiety. Of possible univariate predictors of cessation, including age, years smoking, age of smoking onset, cigarettes/d, previous quit attempts, and Fagerstrom score, only Fagerstrom score (> 7) predicted reduced likelihood of quitting.

Comment by Barbara A. Phillips, MD, MSPH

Nortriptyline has been around a long time, and is a safe and inexpensive drug. As pointed out in the accompanying editorial,1 this study is the third double-blind placebo-controlled study in the peer-reviewed literature to demonstrate that nortriptyline enhances smoking cessation efforts.2,3 The quit rates demonstrated here are similar to those reported in the 2 previous reports. Another antidepressant, buproprion, has also been shown to approximately double long-term cessation rates compared to placebo,4,5 but other antidepressants have not,6 so the effect seen with nortriptyline and buproprion is probably not simply related to the antidepressant effect.

Smoking cessation is big business. A month’s worth of buproprion (Zyban) as marketed for smoking cessation is about $120, and nicotine replacement can range from $55 (for the patch) to $400 (for inhalers) a month. A month’s worth of nortriptyline costs about $6. Since most well-studied pharmacologic treatment of nicotine addiction just about doubles the long-term quit rate (from 10-20%), and because patients should and do keep trying, addition of a cheaper tool in our armamentarium against the leading cause of preventable illness in this country is welcome.

Drugs are probably not the "magic bullet" against nicotine addiction, however. An article in JAMA7 reminds us that nicotine replacement therapy, when sold over the counter, appears to lose its long-term effectiveness. Perhaps good old physician advice is an important part of the treatment.

Dr. Phillips, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington, KY, is Associate Editor of Internal Medicine Alert.


1. DeGraff AC. Chest. 2002;122:392-394.

2. Hall SM, et al. Arch Gen Psychiatry. 1998;55:683-693.

3. Prochazka AV, et al. Arch Intern Med. 1999;159: 1257-1258.

4. Hays JO, et al. Ann Intern Med. 2001;135:423-433.

5. Gonzales DH, et al. Clin Pharmacol Ther. 2001;69: 438-444.

6. Blondal T, et al. Addiction. 1999;94:1007-1015.

7. Pierce JP, Gilpin EA. JAMA. 2002;288:1260-1264.