Mania with bupropion: A dose-related phenomenon?

OBJECTIVE: TO report a case in which bipolar depression was resistant to us ual therapies, requiring dosages of bupropion >450 mg/d and to review the l iterature on mania associated with bupropion and propose a potential theory of a dose-related threshold associated with bupropion and mania. CASE SUMMARY 44-year-old white man with a 25-year history of bipolar affect ive disorder presented with depression resistant to usual therapies. Buprop ion therapy was initiated and the dosage was titrated to 600 mg/d. After ex ceeding the maximum recommended daily dose (450 mg/d), he experienced a man ic episode attributed to high-dose bupropion. DISCUSSION: Due to increased risk of seizures, current prescribing guidelin es state that the total daily dose of bupropion is not to exceed 450 mg/d. Since bupropion is the agent least likely to cause a manic switch in bipola r disorder, mis agent seemed a logical choice tb treat the patient's depres sion. Due to a lack of response. the bupropion dosage was titrated to a max imum of 600 mg/d. Since the patient did not switch into mania until the dos age exceeded 450 mg/d, we speculate that this adverse reaction is a dose-re lated phenomenon. Scientific literature supports this theory. CONCLUSIONS: A switch into mania is a potential risk associated with antide pressant drug use in bipolar affective disorder. Bupropion is believed to b e associated with a decreased risk compared with other antidepressant thera pies. However, our case report as well as others support the theory that th is decreased risk may be due to dosages not exceeding the recommended daily dose (450 mg/d). Doses of bupropion >450 mg/d should be used with caution in depressed patients with bipolar affective disorder.