Bupropion hydrochloride, currently marketed as an antidepressant, is now being reintroduced in a sustained-release formulation to be used as a smoking cessation aid. Bupropion potentiates the effects of norepinephrine and dopamine. Dopamine has been associated with the rewarding effects of addictive substances. It is postulated that inhibition of norepinephrine reuptake might lead to a decrease in withdrawal symptoms. Consultants from The Medical Letter on Drugs and Therapeutics reviewed bupropion as an aid in smoking cessation.

No complete studies have been published to date documenting the effectiveness of bupropion as an aid in smoking cessation. Two studies have been summarized in the manufacturer's prescribing information. One study compared the effects of a seven-week course of 100 mg, 150 mg and 300 mg of sustained-release bupropion with placebo. At the end of treatment, smoking cessation rates with placebo were 17 percent compared with 22 percent, 27 percent and 36 percent with increasing dosages of bupropion. The difference between bupropion in dosages of 150 mg and 300 mg and placebo was statistically significant.

The other study compared the use of transdermal nicotine, sustained-release bupropion, a combination of the two, and placebo. After 10 weeks of treatment, smoking cessation rates were 20 percent with placebo, 32 percent with transdermal nicotine alone, 46 percent with bupropion alone, and 51 percent with transdermal nicotine combined with bupropion. All three active treatments led to a statistically significant difference in smoking cessation rates compared with placebo.

Bupropion is excreted primarily in the urine. With chronic use, plasma concentrations of metabolites of bupropion may increase. Although there has been a concern about seizures with dosages up to 300 mg per day, the incidence has been only about 0.1 percent. The risk might be higher in patients with conditions predisposing to seizures such as alcohol withdrawal, use of cocaine, or anorexia nervosa or bulimia.

Bupropion does not have a sedating effect, although agitation and insomnia have been commonly reported in patients taking the drug for depression. It is not frequently associated with sexual dysfunction, weight gain or anticholinergic effects. Tremor, rash and a few anaphylactoid reactions have been reported. Panic symptoms and psychotic reactions have been reported in patients taking bupropion and fluoxetine concurrently. Bupropion is contraindicated in patients taking monoamine oxidase inhibitors or ritonavir. Carbamazepine increases the metabolism and decreases the antidepressant effect of bupropion.

The recommended dosage in patients attempting smoking cessation is 150 mg once daily for three days and then twice daily for seven to 12 weeks or longer. This regimen may be accompanied by nicotine replacement therapy. Patients are advised to stop smoking during the second week of treatment. The manufacturer offers a counseling and support service. The wholesale cost of a 10-week supply of bupropion is $186.32.

Consultants from the Medical Letter conclude that a two- or three-month course of bupropion, with or without transdermal nicotine replacement therapy, may help to alleviate some of the withdrawal effects from smoking cessation. However, conclusive data have not been published. Long-term relapse rates have been high with use of all smoking cessation agents.

editor's note: A mass marketing blitz is in effect to alert patients to the availability of this drug, and patients are asking their physicians for prescriptions. Until further data are published, the drug should be prescribed with caution and with the understanding that side effects are similar to those occurring with antidepressant dosages. b.a.