INTRAVENOUS CLOMIPRAMINE FOR OBSESSIVE-COMPULSIVE DISORDER REFRACTORYTO ORAL CLOMIPRAMINE - A PLACEBO-CONTROLLED STUDY

Background: Uncontrolled reports suggest that intravenous clomipramine hydrochloride may be effective for patients with obsessive-compulsive disorder (OCD)who are nonresponsive to oral clomipramine. Methods: Fi fty-four patients with oral clomipramine-refractory OCD were randomize d to receive 14 infusions of either placebo or clomipramine hydrochlor ide, starting at 25 mg/d and increasing to 250 mg/d. Ratings were cond ucted double-blind after infusion 14 among 54 patients, single-blind 1 week later among 39 patients, and nonblind 1 month later among 31 pat ients. Response was based on a Clinical Global Impressions rating of a t least ''much improved.'' Results: Six (21%) of 29 patients randomize d to receive intravenous (IV) clomipramine vs 0 of 25 patients given I V placebo were responders after 14 infusions (df=1, P<.02). Dimensiona l racings after infusion 14 revealed significant (P=.007) improvement on the National Institute of Mental Health-Obsessive-Compulsive Scale and the Clinical Global Impressions Scale (P=.03), but not the Yale-Br own Obsessive Compulsive Scale. One week later, all dimensional measur es of OCD showed significant improvement. At 1 week post-IV, 9 (43%) o f 21 patients initially randomized to IV clomipramine and treated subs equently with oral clomipramine were responders, whereas 0 of 18 patie nts initially randomized to receive IV placebo and treated subsequentl y with several days of open-label IV clomipramine responded (df=1, P<. 002). Of the 31 patients assessed 1 month after IV infusion (treatment not controlled), 18 (58.1%) were responders. Intravenous clomipramine treatment was safe with no serious adverse consequences. Conclusions: Intravenous clomipramine is more effective than IV placebo for patien ts with OCD with a history of inadequate response or intolerance to or al clomipramine. further study of this promising treatment fur refract ory OCD is needed.