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• The incidence of suicidal acts was studied in 68 depressed patients and related to the level of 5-hydroxyindoleacetic acid (5HIAA) in the cerebrospinal fluid. The distribution of 5-HIAA levels was bimodal. Patients in the low 5-HIAA mode (below 15 ng/ml) attempted suicide significantly more often than those in the high mode, and they used more violent means. Two of the 20 patients in the low mode, and none of the 48 patients in the high mode died from suicide.

The effect of clomipramine hydrochloride in severe obsessive-compulsive disorder (OCD) was compared with that of nortriptyline hydrochloride and placebo in a five-week randomized, double-blind trial. Clomipramine, but not nortriptyline, was superior to placebo in interview-based ratings of severity of OCD. The effect was not clear-cut until after five weeks of treatment. When clomipramine was given openly to 22 patients after the end of the controlled trial, half of the patients responded to the drug. The response could not be predicted from severity or duration of illness, sex or age of the patient, or presence or absence of secondary depressive symptoms. The amelioration with clomipramine was not sustained if the drug was withdrawn.

Concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the dopamine metabolite homovanillic acid, and the noradrenaline metabolite 4-hydroxy-3-methoxyphenyl 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.