Effects of clomipramine treatment on cerebrospinal fluid monoamine metabolites and platelet 3 H‐imipramine binding and serotonin uptake and concentration in major depressive disorder

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Abstract
In an open study of 12 inpatients who met the DSM‐III criteria for a major depressive episode, the effects of clomipramine (CI) on the monoamine metabolites 5‐hydroxyindoleacetic acid (5‐HIAA), homovanillic acid (HVA), 4‐hydroxy‐3‐methoxyphenyl glycol (HMPG) in cerebrospinal fluid (CSF) were measured simultaneously with the effects on 3H‐imipramine binding, serotonin (5‐HT) uptake and 5‐HT concentration in platelets after 3 and 6 weeks of treatment. Drug (CI and desmethylclomipramine) plasma concentrations were determined. The concentrations of 5‐HIAA and HMPG decreased substantially, and the concentration of HVA remained unchanged. There was also a large and significant reduction of the number of imipramine binding sites (Bmax and of the platelet 5‐HT concentration. The 5‐HT uptake was not measurable after 3 weeks of treatment. None of the parameters changed significantly between weeks 3 and 6. There were no significant correlations between antidepressant effect (measured by the Montgomery‐Åsberg Depression Rating Scale) and plasma drug concentrations, although a tendency to a significant correlation between antidepressant effect and CI was observed at 3 weeks. There were no significant intercorrelations between the different 5‐HT parameters and no other significant correlations between the biochemical measures and clinical outcome.