title: Initial monoamine oxidase-A inhibition by moclobemide does not predict the therapeutic response in patients with major depression. A double blind, randomized study.
abstract: It is generally accepted that the clinical efficacy of monoamine oxidase inhibitors (MAOI) is related to inhibition of this enzyme. In order to evaluate the predictive ability of monoamine oxidase-A inhibition for therapeutic efficacy, the start of treatment effects of moclobemide, a selective, reversible monoamine oxidase-A inhibitor, on plasma concentrations of monoamines and monoamine metabolites were determined. The plasma levels of 3,4-dihydroxyphenylglycol (DHPG, deaminated metabolite of noradrenaline), 5-hydroxyindoleacetic acid (5-HIAA, deaminated metabolite of serotonin), 3,4-dihydroxyphenylacetic acid and homovanillic acid (DOPAC and HVA, deaminated metabolites of dopamine), L-dihydroxyphenylalanine (L-dopa) and noradrenaline were investigated and related to treatment outcome. This was a randomized double blind parallel group study in 47 patients with criteria of major depression according to DSM III R. Moclobemide 300 mg/day, 450 mg/day or 600 mg/day was administered continuously for 6 weeks. Plasma concentrations of monoamine metabolites and monoamines were determined just before treatment by moclobemide, 4 h after the first dose, 24 h after the first dose, before the first dose on day 7, and 4 h after the first dose, on day 7. Each moclobemide dose improved depression as measured by MADRS (Montgomery-Asberg Depression Rating scale) but there was no difference between the three doses. Moclobemide dose-dependently reduced plasma concentration of DHPG, L-dopa and HVA. No dose-dependent treatment effect was observed for plasma 5-HIAA, noradrenaline and DOPAC. The clinical outcome as defined by the final MADRS score was not related to any start of treatment changes in plasma monoamine metabolites reflecting inhibition of MAO-A. It is concluded that monoamine oxidase-A inhibition at the beginning of the treatment does not predict clinical outcome.
authors.affiliation: Department of Psychiatry, Hôpital Saint Antoine, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Radat
authors.forename: I
authors.initials: I
authors.lastname: Berlin
authors.forename: O
authors.initials: O
authors.lastname: Spreux-Varoquaux
authors.forename: S
authors.initials: S
authors.lastname: Elatki
authors.forename: M
authors.initials: M
authors.lastname: Ferreri
authors.forename: A J
authors.initials: AJ
authors.lastname: Puech
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000097:blood; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000097:blood; D008875:Middle Aged; D020912:Moclobemide; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D001549:Benzamides; D015415:Biomarkers; D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D020912:Moclobemide; C010117:3,4-dihydroxyphenylglycol