Background, Aims, and Methods:

Obsessive-compulsive disorder (OCD) is the 4th most common mental disorder in the U.S. and is frequently disabling. From 20% to 40% of OCD patients do not respond satisfactorily to oral medications; patients need an 8- to 10-week trial to determine whether a given drug is effective. This study's broad aims are to investigate the efficacy, safety and rapidity of effect of a new treatment for these patients: pulse-loaded, intravenous clomipramine (CMI).

We are conducting a 2-site, randomized, double-blind controlled trial in 76 patients with treatment- unresponsive DSM-IV OCD comparing pulse loaded i.v. CMI, (day 1, 150 mg; day 2, 200 mg; days 3- 5, zero) to pulse loaded oral CMI (in identical doses) followed by 12 weeks of treatment with oral CMI. Our Primary Hypotheses are:

1. double-blind intravenous pulse loaded CMI will produce by day 6 a clinically meaningful improvement in OCD patients unresponsive to > 2 prior anti-OCD oral drug trials;
2. this improvement will significantly exceed that produced by oral pulse loaded CMI; and,
3. i.v. pulse loading patients will experience greater improvement than oral pulse loading patients after 12-weeks of open-label oral CMI maintenance treatment.

The primary outcome measure is change in Yale Brown Obsessive-Compulsive Scale rating scores obtained by psychiatrists blind to the patient's i.v. versus oral pulse loading group status. We will also explore whether:

1. day 6 and week 12 outcomes are related to plasma levels of CMI and its metabolites; and,
2. outcome can be predicted from baseline clinical information.

For additional information about OCD, its history and treatment, please see the Obsessive-Compulsive and Related Disorders website.