Although many patients with obsessive-compulsive disorder (OCD) benefit from treatment with serotonin reuptake inhibitors (SRIs), it is estimated that 40% to 60% of them do not respond. The objective of the present study was to evaluate the efficacy of quetiapine added to baseline treatment with SRIs for the treatment of OCD in severely ill adult subjects.; Forty patients (21 men, 19 women) with primary OCD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria participated in a 12-week, double-blind, placebo-controlled trial. They were randomly assigned to dosages of quetiapine titrated up to 400 mg/d (n = 20) or to placebo (n = 20) in addition to their SRI treatment. During the continuation phase (weeks 6-12), subjects received different dosages between 400 and 600 mg/d depending on clinical response. At entry, all patients were unresponsive to at least 1 course of at least 12 weeks of treatment with SRIs at defined doses. The total Yale-Brown Obsessive-Compulsive Scale score was the primary efficacy parameter.; Intention-to-treat, last-observation-carried-forward analysis demonstrated a mean +/- SD decrease in Yale-Brown Obsessive-Compulsive Scale score of 5.2 +/- 5.4 in the quetiapine group and 3.9 +/- 4.9 in the placebo group. The analysis of treatment effects between the 2 groups showed no significant difference. There were no significant group differences in any of the other self-rating scales or clinician-administered rating scales.; In this study, augmentation of SRI treatment with quetiapine in severe OCD had no additional effect.