Clomipramine treatment of obsessive-compulsive disorder. II. Biochemical aspects.
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.
D000328:Adult; D002997:Clomipramine / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006018:Glycols / Q000134:cerebrospinal fluid*; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D010648:Phenylacetates / Q000134:cerebrospinal fluid*
D006018:Glycols; D010648:Phenylacetates; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D002997:Clomipramine; D006719:Homovanillic Acid