Bupropion for Smoking Cessation

By William T. Elliott, MD, and James Chan PharmD, PhD


The fda has approved glaxo-wellcome's drug bupropion for the indication of smoking cessation. This represents the first non-nicotine product approved for this indication. Glaxo-Wellcome has marketed bupropion for years for the indication of depression under the trade name Wellbutrin but is now marketing the drug, as a 150 mg sustained-release tablet, under the new name of Zyban. This was done because of concern that the association of a drug with depression management may unfavorably affect the use of bupropion in nondepressed patients wanting to stop smoking.

The drug represents a unique approach to the problem of smoking cessation. Nicotine addiction seems to affect dopamine and norepinephrine pathways in the brain, the same neurotransmitters that may be affected by bupropion.1 Another unique property of the drug is the ability to start treatment one week before quitting, an option not available with nicotine replacement products.

Indications

Bupropion is indicated as an aid to smoking cessation.

Potential Advantages

Bupropion represents a distinctive approach to smoking cessation since it is the first non-nicotine product for this indication. In a comparative trial involving nondepressed chronic smokers who smoked 15 cigarettes/day, bupropion (300 mg/d) was more effective than nine weeks of a tapering nicotine patch regimen or placebo. The quit rates at 10 weeks were: bupropion, 46%; nicotine patch, 32%; and placebo, 20%. The combination of bupropion and nicotine patch achieved a quit rate of 51%, which was not statistically different from bupropion alone. All patients received a brief (5-10 minutes) individual smoking cessation and relapse prevention counseling session through the end of follow-up.1

Bupropion has been reported to reduce withdrawal symptoms such as irritability, frustration, anxiety, difficulty in concentration, restlessness, and depressed mood or negative affect.1

Glaxo-Wellcome has packaged the drug with written stop-smoking support material and a toll-free number to obtain counseling support.

Potential Disadvantages

Long-term effectiveness of bupropion has not been determined, but in a placebo-controlled trial, the quit rate at six months was only 19% compared to 11% for placebo.

Adverse events led to discontinuation of treatment in 8% of patients. The most common side effect associated with bupropion is insomnia, reported by 40% of patients. Other side effects include nervous system disturbances, primary tremors, and skin rash.

Bupropion is associated with a dose-dependent risk of seizures, and doses over 300 mg should not be prescribed for smoking cessation. The drug should also be used with extreme caution in patients with a history of seizures or who are on treatment regimens that may lower seizure threshold.1

Dosing Information

Bupropion as Zyban is supplied in 150 mg sustained-release tablets.

The initial dose is 150 mg for the first three days followed by an increase to the usual dose of 300 mg/d. Treatment should be initiated while the patient is still smoking and continued for about one week to achieve steady-state blood levels of bupropion before quitting is attempted.

Comments

Bupropion is the first non-nicotine replacement product approved for smoking cessation. The mechanism of action of bupropion is believed to involve dopaminergic and/or noradrenergic pathways in the brain. In smokers, nicotine releases neurochemicals including dopamine, norepinephrine, and serotonin, an effect that is similar to the action of some antidepressants.2 Animal studies suggest that the mesolimbic dopamine system is important in reinforcing the effect of nicotine.3 There also appears to be a high incidence of depression in smokers, and depressed patients find it very difficult to quit smoking.4 Bupropion has established efficacy, at least in the short term, in helping nondepressed smokers quit smoking, and it may offer help for depressed patients as well.

The daily cost for bupropion as Zyban is $2.55/day, which is similar to the daily cost of the nicotine patch. Most patches are now available over the counter. Bupropion as Wellbutrin SR is priced the same as Zyban.

Clinical Implications

Bupropion offers a unique mechanism of action for smokers who wish to quit. Its short-term efficacy is at least as good as the nicotine patch; however, long-term efficacy has not been established.

References

    1. Zyban Product Information. Glaxo-Wellcome. May 1997.

    2. Benowitz NL. Annu Rev Pharmacol Toxicol 1996;36: 597-613.

    3. Corrigall WA, et al. Brain Res 1994;653:278-284.

    4. Hall SM, et al. J Consult Clin Psychol 1993;61-67.