Nortriptyline

As a treatment for depression, drugs such as Prozac, which boost activity of the neurotransmitter serotonin, have in the past few years largely replaced tricyclic antidepressants, which increase the action of the neurotransmitter dopamine. But at least one tricyclic medication now shows signs of life as an aid to cigarette smokers who want to kick their habit, according to a new study.

More cigarette smokers given nortriptyline for 3 months remained abstinent over the following year than smokers provided with pills having no active ingredient, report psychologist Sharon M. Hall of the University of California, San Francisco and her colleagues. Nortriptyline treatment increased abstinence among smokers who had not experienced prior bouts of severe depression, the researchers note.

This finding comes on the heels of evidence that bupropion, a dopamine-enhancing drug but not a tricyclic, also increases abstinence in those trying to quit cigarettes (SN: 11/15/97, p. 319). Bupropion, which is more expensive than nortriptyline, has been approved by the Food and Drug Administration for use in programs to help people stop smoking.

"The outcome data suggest that nortriptyline is a useful adjunct to smoking cessation efforts," Hall and her coworkers conclude in the August Archives of General Psychiatry.

Through public service and newspaper ads, the scientists recruited 199 men and women, all of whom smoked 10 or more cigarettes daily. None exhibited symptoms of major depression, but 65 had been diagnosed with it previously.

Volunteers were randomly assigned to nortriptyline or placebo treatment. All attended eight weekly group sessions that focused either on monitoring abstinence efforts or promoting positive thoughts and activities linked to a nonsmoking way of life. These group sessions took place during the last 2 months of treatment, allowing nortriptyline the several weeks required to begin exerting its effects.

Abstinence was confirmed by urine analyses at the end of treatment and at three points during the following year.

Among participants with no history of depression, slightly more than 40 percent of those who received nortriptyline remained abstinent after 1 year. Around one-quarter of those who received placebos ended up cigarette-free. In neither case was there a difference attributable to which group sessions participants had attended.

Among previously depressed volunteers, the type of group sessions made a difference. About one-third of those who attended sessions that emphasized mood-boosting strategies were abstinent after 1 year in both the nortriptyline and placebo groups. Those who attended the other type of sessions achieved much lower abstinence rates, regardless of which type of pill they had received.

Self-reported mood in the first 3 days after quitting cigarettes was brighter for those who took the antidepressant, which may have increased their likelihood of achieving short-term abstinence.

However, it's tough to give up cigarettes for good. A majority of participants, including those given nortriptyline, resumed smoking after 1 year.

Scientists need to look for specific dopamine-enhancing actions of nortriptyline and bupropion that influence smoking abstinence, holds psychiatrist Alexander H. Glassman of Columbia University in a commentary accompanying Hall's findings. Indirect evidence for a dopamine role comes from three unpublished clinical trials, conducted several years ago, which found that Prozac and related serotonin boosters offer no help to those trying to quit cigarettes, Glassman says.

Drugs such as nortriptyline may help cigarette smokers negotiate the long process of dumping their habit, which typically includes seven or eight unsuccessful attempts, comments psychiatrist John R. Hughes of the University of Vermont in Burlington.

"Nortriptyline and bupropion treatment may prompt more quitting attempts by smokers," Hughes says. "Every time someone quits and fails, they learn something about their cigarette cravings that makes them more likely to quit for good on the next try."

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