OBJECTIVE: The authors conducted a randomized, double-blind, placebo- controlled trial of intravenous versus oral pulse loading of clomipramine in patients with obsessive-compulsive disorder to test two hypotheses: 1) intravenous pulse loading will cause greater immediate improvement than oral pulse loading and 2) patients who respond to pulse loading will continue to improve during 8 weeks of oral clomipramine treatment. METHOD: Fifteen patients with DSM-III-R obsessive-compulsive disorder of at least 1 year's duration and baseline Yale-Brown Obsessive Compulsive Scale scores of 17 or higher were enrolled in the study. Yale-Brown scale ratings were made 4.5 days after double-blind oral or intravenous pulse loading of clomipramine, and patients were then given 150 mg/day of oral clomipramine with increases of 25 mg every 4 days to 250 mg/day as tolerated or, in two cases, other selective serotonin reuptake inhibitors (SSRIs). RESULTS: The first hypothesis was confirmed: 4.5 days after the second pulse- loaded dose, six of seven patients given intravenous clomipramine but only one of eight given oral medication responded to the drug. After 8 weeks of oral clomipramine, the results partially supported the second hypothesis: four of six patients who had responded to intravenous clomipramine continued their improvement, but those who had responded to pulse loading did not improve statistically significantly more than those who had not. CONCLUSIONS: Intravenous pulse loading of clomipramine may be a valuable new treatment for obsessive-compulsive disorder, particularly for patients who have failed oral treatment trials.Abstract Teaser