Bupropion (Wellbutrin) has been available in the United States since 1989 for the treatment of major depression. The actual incidence and severity of bupropion exposures are unknown because the AAPCC-TESS data do not include a separate category for bupropion exposures. However, since bupropion has recently been approved for the treatment of smoking cessation (Zyban), the potential for bupropion poisoning is considerable. Both Wellbutrin and Zyban tablets are manufactured by the same company and are available in similar 150-mg sustained-release formulations. For smoking cessation, Zyban (150 mg) is administered either once or twice daily for no more than 12 consecutive weeks. Wellbutrin comes in a variety of doses and formulations, including sustained-release tablets (100 and 150 mg) and regular-release tablets (100 and 75 mg). The recommended starting dose of Wellbutrin is 100 mg given twice daily, gradually increasing up to 300 mg/day. The incidence of seizures drastically increases at doses greater than 450 mg/day, and higher doses are therefore prohibited. The combination of the two bupropion preparations, Wellbutrin and Zyban, is contraindicated due to obvious concern for bupropion toxicity. Other contraindications include patients with bulimia, anorexia nervosa, epilepsy, or taking MAOIs. Bupropion is a category B drug in pregnancy. The information in this section is derived from studies utilizing only the Wellbutrin form of bupropion. It is assumed that this information is equally applicable to Zyban exposures, and therefore no further distinction in this chapter is made between these two bupropion products.
Bupropion has a monocyclic phenylaminoketone chemical structure that resembles those of the phenylethylamines (e.g., amphetamine).4 However, bupropion does not produce stimulant effects or drug-addictive behavior at therapeutic doses. The therapeutic mechanism of action for bupropion is poorly understood but currently believed to be related to its ability to inhibit dopamine neuronal reuptake. It does not directly stimulate postsynaptic dopamine receptors. In vitro studies show bupropion to be a weak inhibitor of norepinephrine and serotonin neuronal reuptake. Bupropion is rapidly absorbed after oral administration and undergoes extensive first-pass hepatic metabolism. It is highly protein bound, has an extremely large volume of distribution, and readily crosses the blood-brain barrier. Peak plasma levels occur within 2 h for regular-release tablets and 3 h for sustained-release preparations. Its elimination half-life ranges between 14 to 20 h. Bupropion has one important metabolite—hydroxybupropion—which is less potent than bupropion, preferentially inhibits norepinephrine reuptake, and may contribute to seizure development.
Bupropion antidepressant therapy is well tolerated. It does not produce CNS depression, orthostatic hypotension, or cardiovascular changes, or impair sexual function at therapeutic doses. The most commonly reported adverse effects are of mild severity and include dry mouth, dizziness, agitation, nausea, headache, constipation, tremor, anxiety, confusion, blurred vision, and increased motor activity. Bupropion has been reported to infrequently produce catatonia, hallucinations, psychosis, and paranoia that are probably related to its dopaminergic activity.
Abrupt discontinuation of bupropion has not been associated with any withdrawal symptoms but may pose a slight theoretic risk of precipitating neuroleptic malignant syndrome, since bupropion is considered a dopamine agonist. Bupropion is relatively free of significant drug interactions. In general, bupropion should not be combined with selective serotonin reuptake inhibitors, lithium, MAOIs, TCAs, dopaminergic drugs (e.g., levodopa), or drugs that are known to lower patient seizure threshold (e.g., phenothiazines).
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