During the clinical development of bupropion (Wellbutrin) 1,153 depressed patients and 157 normal volunteers received bupropion (doses, 15-1200 mg/day); 177 placebo-treated and 196 tricyclic-treated patients (doses, 25-300 mg/day) also participated in these trials to provide a control comparison. Safety measures during the clinical trial program included adverse event symptomatology, vital signs, clinical laboratory examinations, and EEGs. There were no bupropion-related changes in vital signs, clinical laboratory, or EEG results severe enough to warrant treatment discontinuation. The most common cause for discontinuation in the bupropion (9.1%), placebo (6.8%), and tricyclic groups (9.2%) was agitation/excitement. The only adverse experience considered of medical significance in bupropion patients was major motor seizure. The incidence of a seizure was less than 1 per 1,000 at usual outpatient doses and less than 1 per 100 at usual inpatient doses. These incidences appear to be comparable to those seen with equally therapeutic doses of tricyclic antidepressants.