Bupropion differs from other new antidepressants in that it has a low toxic to therapeutic ratio. Toxicity can occur at doses equal to or just slightly greater than the maximum therapeutic dose of 450 mg/day. As a general rule, significant toxicity is not expected in pure bupropion overdose with adult ingestions of less than 450 mg. The largest case series of bupropion overdoses reported that symptomatic patients ingested a mean of 2310 mg and the lowest symptomatic dose was 200 mg.5 Patients who remained asymptomatic ingested a mean of 1325 mg and the largest asymptomatic dose was 4000 mg. The most commonly reported symptoms in pure bupropion overdose include sinus tachycardia (43 percent), lethargy (41 percent), tremor (24 percent), generalized seizures (21 percent), confusion (14 percent), and vomiting (14 percent). Mild hyperthermia is occasionally reported. Sinus tachycardia is the most common electrocardiographic abnormality. An isolated case of moderate QT interval prolongation has been reported in conjunction with a massive bupropion overdose. Otherwise, bupropion does not produce myocardial conduction abnormalities. Hypotension is unexpected in pure bupropion overdoses but has been reported in mixed-drug overdoses. Hypertension is usually of only mild to moderate severity. Coma and cardiac arrest have been reported in severe bupropion overdoses. The hallmark of bupropion toxicity is generalized seizures. The actual incidence of seizures is unknown but is probably greater than the estimated 21 percent obtained by retrospective studies. There is no correlation between the development of seizures and the presence of other symptoms such as sinus tachycardia. Therefore, seizures can develop in otherwise asymptomatic patients. Seizures usually occur within the first 1 to 4 h after ingestion of regular-release bupropion. The average time of seizure onset is 3.7 h, but they may be delayed for up to 8 h. Recent case reports suggest that sustained-release preparations may predispose patients to seizures up to 14 h after exposure. Laboratory study findings are usually normal except for rare cases of mild hypokalemia.
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