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

Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, CA 94305, USA.
Journal of Clinical Psychopharmacology (Impact Factor: 3.24). 03/2006; 26(1):79-83. DOI: 10.1097/
Source: PubMed


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.
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.
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 > or =1-year duration and Yale-Brown Obsessive Scale score of > or =20. Eligible subjects had failed > or =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.
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.
Further investigation of oral pulse-loading regimens in treatment-resistant obsessive-compulsive disorder is warranted.

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    • "Intravenous (IV) CMI has been studied in adults, on an investigational basis, typically in inpatients with severe OCD not responsive to multiple prior medication trials, including oral CMI.82–84 IV CMI may be better tolerated than the oral form and it provides 4- to 14-fold higher peak plasma concentrations.83 Response rates in this highly refractory population have been low; for instance, in one placebo-controlled study of 46 patients, 21% of treated patients versus 0% of controls were responders after 2 weeks of daily infusions, with 58% maintaining responder status on oral CMI 1 month later.85 "
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    • "However , high dosages of sertraline and possibly citalopram can generate the same phenomenon (Preskorn, et al., 2007; Gillman, 2007; Mandrioli, et al., 2006). Still, no consistent relationship between magnitude or probability of therapeutic response in OCD and plasma concentrations of clomipramine or its metabolite or their sum has been found (Koran, et al., 2006). "
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