Drugs

, Volume 59, Issue 4, pp 1007–1024 | Cite as

Bupropion

A Review of its Use in the Management of Smoking Cessation
Adis Drug Evaluation

Summary

Abstract

Sustained release bupropion (amfebutamone) is a non-nicotine agent that is indicated as an aid to smoking cessation.

In 2 large well designed clinical trials, sustained release bupropion 300 mg/day (the recommended dose) for 7 or 9 weeks was associated with considerably and significantly higher smoking abstinence rates (continuous abstinence and 7-day point prevalence rates) than placebo during treatment and at follow-up at 6 and 12 months. Point prevalence rates at 12 months in 2 studies were 23.1 and 30.3% with bupropion, whereas values for placebo were 12.4 and 15.6%. Continuous abstinence rates at 12 months, available from 1 trial, were 18.4% with bupropion and 5.6% with placebo. Furthermore, bupropion was associated with significantly higher quitting rates than nicotine patch in a comparative study. Combination therapy with bupropion and nicotine patch provided slightly higher abstinence rates than bupropion alone, although differences were not statistically significant. The combination was superior to nicotine patch alone.

Data from a preliminary report of long term bupropion treatment (52 weeks) showed that the drug was associated with significantly higher continuous abstinence rates than placebo only to 6 months. However, point prevalence abstinence rates were significantly higher with bupropion than placebo to 18 months.

Bupropion 300 mg/day recipients reported nicotine withdrawal symptoms during treatment; however, the symptoms were significantly less severe with bupropion than placebo. Patients receiving bupropion 300 mg/day or bupropion in combination with nicotine patch for smoking cessation generally gained less body weight than placebo recipients. The benefits of bupropion for preventing weight gain persisted after the completion of long term, but not short term therapy.

Bupropion was well tolerated in clinical trials, and the only adverse events that were significantly more common with bupropion than placebo were insomnia and dry mouth. Data published so far suggest that sustained release bupropion has a low potential for inducing seizures (seizure rate ≈0.1% in patients with depression).

Conclusions: Bupropion is an effective and well tolerated smoking cessation intervention. Further studies with long term follow-up will be useful in determining whether abstinence rates are maintained with bupropion. In addition, clarification of its efficacy in comparison with other therapies used for smoking cessation would help to establish its clinical value. The reduced potential for weight gain with bupropion and the ability to use bupropion in combination with nicotine replacement therapy make the drug a useful treatment option for smoking cessation.

Pharmacology

The mechanism by which bupropion (amfebutamone) acts as an aid in smoking cessation is unknown. However, bupropion is thought to produce its therapeutic antidepressant effects via the inhibition of noradrenaline and/or dopamine reuptake. Bupropion does not affect serotonin reuptake.

Bupropion showed dependence potential in animal models, but not at therapeutic dosages in individuals who abuse drugs or in healthy volunteers. Post-marketing surveillance data have shown that bupropion has a very low abuse potential.

Maximum plasma concentrations of sustained release bupropion are reached approximately 3 hours after an oral 150mg dose. Bupropion is highly plasma protein bound, and is extensively metabolised to 3 active metabolites. A single 150mg dose of sustained release bupropion has a mean elimination half-life of 18 to 19 hours. Around 84% and 9% of an oral dose of bupropion was recovered in the urine and faeces, respectively, within 72 hours after administration.

There is little available data on the effects of the concomitant administration of bupropion and other drugs on the metabolism of each drug. However, there is potential for interactions between bupropion and drugs that affect the cytochrome P450 (CYP) 2B6 isoenzyme. In addition, bupropion inhibits the activity of the CYP2D6 isoenzyme, which metabolises certain antidepressants (including tricyclic antidepressants and selective serotonin reuptake inhibitors), β-blockers, antiarrhythmics and antipsychotics. It is recommended that coadministration of bupropion and such drugs is approached with caution.

There are no significant differences in the pharmacokinetics of sustained release bupropion between smokers and nonsmokers. Sustained release bupropion is bioequivalent to the immediate release formulation in humans.

Therapeutic Efficacy

Sustained release bupropion 300 mg/day for 7 or 9 weeks significantly increased smoking cessation rates (continuous abstinence and 7-day point prevalence rates) during treatment and at follow-up at 6 and 12 months versus placebo in 2 large well designed studies. Point prevalence rates at 12 months were ≤30.3% with bupropion, whereas values for placebo were ≤15.6%. In 1 trial, continuous abstinence rates at 12 months were 18.4% with bupropion and 5.6% with placebo. Furthermore, bupropion was associated with significantly higher quitting rates than nicotine patch in the only comparison. Combination therapy with bupropion and nicotine patch provided slightly higher abstinence rates than bupropion alone, although differences were not statistically significant. The combination was superior to nicotine patch alone.

Data from a preliminary report of long term bupropion treatment (52 weeks) showed that the drug was associated with significantly higher continuous abstinence rates than placebo only to 6 months. However, point prevalence abstinence rates were significantly higher with bupropion than placebo to 18 months.

Bupropion 300 mg/day recipients reported significant withdrawal symptoms during treatment; however, the symptoms were significantly less with bupropion than placebo. In the preliminary report of a long term (52 weeks’ treatment) study, bupropion recipients had significantly less craving for cigarettes than placebo recipients and craving was less likely to be the reason for relapse with bupropion than placebo.

Bodyweight gain was generally less in patients receiving bupropion 300 mg/day or bupropion in addition to nicotine patch for smoking cessation than in placebo recipients. The benefits of bupropion for preventing weight gain persisted after the completion of long term, but not short term therapy.

Tolerability

Short term treatment with sustained release bupropion 300 mg/day was well tolerated in clinical trials of the drug for smoking cessation. The only adverse events that were significantly more common with bupropion than placebo were insomnia and dry mouth. Sustained release bupropion appears to have a lower propensity to cause seizures than the immediate release formulation (≈0.1 vs 0.4% for therapeutic dosages); however, no direct comparison of seizure rates between the formulations has been made.

Immediate release bupropion was generally well tolerated in patients with pre-existing heart disease. The cardiovascular effects of bupropion have not been assessed in patients with unstable heart disease or recent myocardial infarction, although studies are ongoing.

Dosage and Administration

It is recommended that sustained release bupropion 300 mg/day (twice daily) is given for 7 to 12 weeks for smoking cessation in adults. A target quitting date should generally be set for within the first 2 weeks of treatment. Patients are able to continue smoking while they take bupropion. In patients requiring continuous treatment, bupropion can be continued for up to 6 months (US) or a year (Canada). Bupropion can be given with transdermal nicotine. Patients with hepatic or renal disease should be treated with reduced dosages of bupropion.

Bupropion is contraindicated in patients with bulimia or anorexia nervosa and in patients with seizure disorders. In addition, bupropion should be given with caution to patients with risk factors for seizures. Mothers should not continue breastfeeding infants while taking bupropion.

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© Adis International Limited 2000

Authors and Affiliations

  1. 1.Adis International LimitedMairangi Bay, AucklandNew Zealand

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