Pulse-loaded intravenous clomipramine in treatment-resistant obsessive-compulsive disorder

Introduction: Small studies have suggested that intravenous clomipramine (CMI) may be more effective and induce faster improvement in obsessive-compulsive disorder than do orally administered serotonin reuptake inhibitors. Objective: To test these hypotheses, we conducted a randomized, double-blind, double-dummy study of pulse-loaded intravenous versus oral CMI, followed by open-label oral CMI for 12 weeks. Methods: We enrolled a volunteer and referred group of 34 adults with a primary diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition obsessive-compulsive disorder of >= 1-year duration and Yale-Brown Obsessive Scale score of >= 20. Eligible subjects had failed >= 2 adequate serotonin reuptake inhibitor trials. Subjects received pulse loaded CMI 150 mg by vein or by mouth on day 1 and 200 mg on day 2. Oral CMI began on day 6 at 200 mg/d and was increased by 25 mg every 4 days to 250 mg/d, as tolerated, for 12 weeks. Results: Adverse events led to one withdrawal during oral pulse loading and 5 during open-label oral treatment. Intravenous pulse loading did not induce a more rapid or greater Yale-Brown Obsessive Scale score decrease than oral pulse loading at day 6 or by week 12. Day 6 and week 12 improvement were unrelated to plasma drug or metabolite concentrations. Pulse loading itself seemed to induce more rapid and greater improvement than expected in treatment-resistant obsessive-compulsive disorder. Conclusions: Further investigation of oral pulse-loading regimens in treatment-resistant obsessive-compulsive disorder is warranted.