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IV Clomipramine for Psychiatric Disorders

Although most psychiatrists do not use intravenous medications routinely, two recent double-blind, placebo-controlled studies suggest that IV clomipramine may have some clinical utility.

Researchers in the first study randomized 15 inpatients with obsessive compulsive disorder (OCD) for at least one year to receive either two days of IV pulse loading of clomipramine (150 mg) plus oral placebo or 150 mg of oral clomipramine plus IV placebo. Four and a half days after the second pulse-loaded dose, all patients received 150 mg of oral clomipramine increased every four days by 25 mg to 250 mg or as tolerated (two patients were switched to other SSRIs). The two groups had similar ages, duration of illness, previous treatment failures on clomipramine, and mean Yale Brown Obsessive Compulsive Scale (YBOCS) scores.

Four and a half days after pulse loading, 6 of 7 IV-treated patients versus only 1 of 8 patients on oral medication experienced at least 25% reduction in YBOCS scores (average decrease, 40.8%). After eight weeks of oral treatment, 4 of the 6 initial IV responders had a good response versus only 3 of the 7 patients who had an initial poor response to the oral drug. Several patients who were previously nonresponders to oral clomipramine had positive responses to IV medication.

The second study randomized 16 nonsuicidal depressed adolescent outpatients to receive either a single IV pulse of clomipramine (200 mg) or placebo. HAM-D scores significantly improved in the clomipramine group after six days.

Comment: The rapid response to IV clomipramine in the OCD patients is most likely due to plasma levels 4 to 14 times as high as those obtained with oral dosing and consequently much higher brain levels. Although this technique is unlikely to become routine, pulse loading may permit rapid identification of OCD treatment responders, increase compliance by demonstrating rapid symptom improvement, and be useful for treatment-resistant OCD patients. While other studies have failed to report outcome differences between IV and oral pulse loading of clomipramine for the treatment of depression, it may be that, in contrast to OCD, adequate plasma levels for treating depression are achieved by both routes.

— J Yager

Published in Journal Watch Psychiatry August 1, 1997

Citation(s):

Koran L et al. Rapid benefit of intravenous pulse loading of clomipramine in obsessive-compulsive disorder. Am J Psychiatry 1997 Mar 154 396-401.

• Medline abstract (Free)

Sallee FR. Pulse intravenous clomipramine for depressed adolescents: Double-blind, controlled trial. Am J Psychiatry 1997 May 154 668-673.

• Medline abstract (Free)