Effects of clomipramine treatment on cerebrospinal fluid monoamine metabolites and platelet 3H-imipramine binding and serotonin uptake and concentration in major depressive disorder.
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-Asberg 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.
Mårtensson
B
B
Department of Psychiatry and Psychology, Karolinska Hospital, Stockholm, Sweden.
Wägner
A
A
Beck
O
O
Brodin
K
K
Montero
D
D
Asberg
M
M
D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins; D002997:Clomipramine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000134:cerebrospinal fluid*; D011569:Psychiatric Status Rating Scales; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000097:blood*
D002352:Carrier Proteins; D018377:Neurotransmitter Agents; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; C027775:imipramine receptor; C012273:desmethylclomipramine; D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D002997:Clomipramine; D006719:Homovanillic Acid