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II. Biochemical Aspects

Peter Thorän, MD; Marie Åsberg, MD; Leif Bertilsson, PhD; Britt Mellstrüm, MPharm; Folke Sjüqvist, MD; Lil Träskman, MB

Arch Gen Psychiatry. 1980;37(11):1289-1294.

Abstract
• 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.

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).

Footnotes
Accepted for publication March 20, 1980.

Reprint requests to Psychiatric Clinic, Karolinska Hospital, S-104 01 Stockholm 60, Sweden (Dr Åsberg).

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