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November 1980

Clomipramine Treatment of Obsessive-Compulsive Disorder: II. Biochemical Aspects

Author Affiliations

From the Department of Psychiatry, Karolinska Hospital, Karolinska Institute, Stockholm (Drs Thorän, Åsberg, and Träskman); and the Department of Clinical Pharmacology, Huddinge Hospital, Karolinska Institute, Huddinge, Sweden (Drs Bertilsson, Mellstrüm, and Sjüqvist).

Arch Gen Psychiatry. 1980;37(11):1289-1294. doi:10.1001/archpsyc.1980.01780240087010

• Concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the dopamine metabolite homovanillic acid, and the noradrenaline metabolite 4-hydroxy-3-methixyphenyl glycol were measured in CSF before and after three weeks' treatment of severe obsessive-compulsive disorder with clomipramine hydrochloride. Patients who responded to clomipramine treatment had significantly higher CSF levels of 5-HIAA before treatment. The amelioration of obsessive-compulsive symptoms was positively correlated to the reduction of CSF concentrations of 5-HIAA during clomipramine treatment but negatively correlated to plasma concentrations of clomipramine. Reduction of CSF concentrations of 5-HIAA, which probably reflects drug action on central serotonin neurons, was maximal at a plasma clomipramine concentration of about 300 nmole/L. At higher levels, the reduction of CSF levels of 5-HIAA was smaller. The antiobsessive effect of clomipramine may be connected to its capacity to inhibit serotonin uptake.

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