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).


METHODS
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.


CONCLUSIONS
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.
Dunner
D L
DL
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle 98105, USA.
Zisook
S
S
Billow
A A
AA
Batey
S R
SR
Johnston
J A
JA
Ascher
J A
JA
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects* / Q000627:therapeutic use; D016642:Bupropion / Q000009:adverse effects* / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011358:Product Surveillance, Postmarketing; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012640:Seizures / Q000139:chemically induced* / Q000453:epidemiology; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D003692:Delayed-Action Preparations; D016642:Bupropion