Objective: To evaluate the efficacy and safety of high-dose sertraline for patients with obsessive-compulsive disorder (OCD) who failed to respond to standard sertraline acute treatment.

Method: Sixty-six nonresponders to 16 weeks of sertraline treatment who met DSM-III-R criteria for current OCD were randomly assigned, in a double-blind continuation phase of a multicenter trial, either to continue on 200 mg/day of sertraline or to increase their dose to between 250 and 400 mg/day for 12 additional weeks. Efficacy measures included the Yale-Brown Obsessive Compulsive Scale (YBOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH Global OC Scale), and the Clinical Global Impressions-Severity of Illness and -Improvement (CGI-I) scales. Data were collected from July 26, 1994, to October 26, 1995.

Results: The high-dose (250-400 mg/day, mean final dose= 357, SD = 60, N = 30) group showed significantly greater symptom improvement than the 200-mg/day group (N = 36) as measured by the YBOCS (p=.033), NIMH Global OC Scale (p = .003), and CGI-I (p = .011). Responder rates (decrease in YBOCS score of > = 25% and a CGI-I rating < = 3) were not significantly different for the 200-mg/day versus the high-dose sertraline group, either on completer analysis, 34% versus 52%, or on endpoint analysis, 33% versus 40%. Both treatments showed similar adverse event rates.

Conclusion: Greater symptom improvement was seen in the high-dose sertraline group compared to the 200-mg/day dose group during continuation treatment. Both dosages yielded similar safety profiles. Administration of higher than labeled doses of selective serotonin reuptake inhibitors may be a treatment option for certain OCD patients who fail to respond to standard acute treatment.

(J Clin Psychiatry 2006;67:15-22)