A prospective safety surveillance study for bupropion sustained-release in the treatment of depression.

BACKGROUND: This prospective 105-site study was conducted to determine the rate of seizures and other serious adverse experiences associated with the therapeutic use of the sustained-release formulation of bupropion (bupropion SR). METHOD: 3100 patients with a DSM-III-R diagnosis of depression without a current or past diagnosis of an eating disorder and with no personal or family history of seizure disorders were treated for up to 8 weeks with bupropion SR in an open-label study. Dosing was initiated at 50 mg b.i.d. and increased to a maximum of 150 mg b.i.d. unless not tolerated. Patients had the option to continue treatment with bupropion SR (50 mg b.i.d. to 150 mg b.i.d.) in a continuation phase lasting up to 1 year. During the acute and continuation phases, patients were evaluated for the occurrence of seizures and other serious adverse experiences. Clinical response to and tolerability of bupropion SR were also evaluated. RESULTS: Three patients each experienced a seizure associated with the therapeutic use of bupropion SR during the acute and continuation phases combined. The observed seizure rate during the 8-week acute phase was 2 seizures in 3094 evaluable patients, or 0.06%. The observed seizure rate for the acute and continuation phases combined was 3 seizures in 3094 patients, or 0.10%. Survival analysis yielded a cumulative seizure rate of 0.08% for the acute phase and 0.15% for both phases combined. Two patients who intentionally overdosed with bupropion SR also experienced seizures; however, these events were not included in calculations of the overall seizure rate. Therapeutic doses of bupropion SR were well tolerated and clinically efficacious. CONCLUSION: The therapeutic use of bupropion SR at total daily doses up to 300 mg/day in depressed patients without predisposition to seizures is associated with a seizure rate that is well within the range observed with other marketed antidepressants.

Comparison of bupropion and trazodone for the treatment of major depression.

Bupropion and trazodone were compared in a two-center, double-blind clinical trial of outpatients with moderate to severe major depression. After a 1-week placebo lead-in, 124 patients were randomly assigned to receive either bupropion (N = 63) or trazodone (N = 61) for 6 weeks; data from 111 patients were used in the efficacy analysis. Dosing ranged from 225 to 450 mg/day for bupropion and 150 to 400 mg/day for trazodone. The overall efficacy for each of the two drugs was similar; although improvement in the trazodone treatment group was significantly greater on day 7 because of the effects on sleep. At the end of treatment, 58% of the bupropion-treated patients and 46% of the trazodone-treated patients were considered much or very much improved. Weight measurements at the time of discontinuation indicated a 2.5-lb mean weight loss for the bupropion treatment group and a 1.2-lb mean weight gain for the trazodone treatment group. The adverse experience profiles for bupropion and trazodone were consistent with their known pharmacologic profiles (i.e., activating versus sedating). Anorexia and anxiety were reported significantly more often for the bupropion treatment group, whereas somnolence, appetite increase, and edema were reported significantly more often for the trazodone treatment group.