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October 1990

Controlled Comparisons of Clomipramine and Fluoxetine in the Treatment of Obsessive-Compulsive Disorder: Behavioral and Biological Results

Author Affiliations

From the Laboratory of Clinical Science (Drs Pigott, Pato, Hill, and Murphy, and Mss Bernstein and Tolliver), and the Nursing Department (Ms Grover), National Institute of Mental Health, Bethesda, Md.

Arch Gen Psychiatry. 1990;47(10):926-932. doi:10.1001/archpsyc.1990.01810220042005

• Treatment with fluoxetine hydrochloride was compared with treatment with clomipramine hydrochloride in two groups of patients with obsessive-compulsive disorder using two different experimental designs. In the first group of 11 patients with obsessive-compulsive disorder studied using a randomized, doubleblind, crossover design, treatment with fluoxetine for 10 weeks was found to produce therapeutic effects similar to treatment with clomipramine for 10 weeks. There were significantly fewer total side effects reported during fluoxetine than clomipramine treatment. Drug tapering and placebo substitution in the 4-week crossover interval phase led to substantial relapses in obsessive-compulsive disorder symptoms and depression. Furthermore, responses to the second drug took as long to occur as responses to the first drug, although both drugs are thought to act by a common mechanism, serotonin uptake inhibition. A second group of 21 patients with obsessive-compulsive disorder that had been previously stabilized on clomipramine treatmen with at least partial benefit were crossed over to fluoxetine treat ment in a double-blind fashion. After 10 weeks of fluoxetine administration, most patients manifested behavioral rating scores of obsessive-compulsive disorder and depressive symp toms that were comparable with precrossover ratings complete during clomipramine treatment. A significant exacerbation ir obsessive-compulsive disorder and depression ratings as wel as a similar lag in therapeutic efficacy were also noted in this second cohort of patients with obsessive-compulsive disorder Platelet 5-HT concentrations were reduced 95% during both clo mipramine and fluoxetine treatment periods. These results sug gest that fluoxetine may represent a viable alternative to clomip ramine in the treatment of obsessive-compulsive disorder, al though further studies with larger sample sizes are needed.

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