title: Monoamine oxidase inhibitors phenelzine and brofaromine increase plasma serotonin and decrease 5-hydroxyindoleacetic acid in patients with major depression: relationship to clinical improvement.
abstract: We have examined the effects of two monoamine oxidase (MAO) inhibitors with different mechanisms of action--phenelzine and brofaromine--on peripheral serotonergic (5-hydroxytryptamine [5-HT]) measures, sensitive to the inhibition of MAO-A (intra- and extracellular 5-HT and related metabolites in blood). Both drugs increased the concentration of 5-HT in platelet-free plasma (254%, p less than 0.001) in patients with depressive illness (DSM-III-R) after 6 weeks of daily treatment. Platelet 5-HT was also increased significantly in both drug treatment groups but more marked in the patient group treated with phenelzine. The acid/amine ratio at 6 weeks was 30% of pretreatment values (p less than 0.000) and individual variability correlated significantly with the Hamilton Rating Scale for Depression. Plasma 5-HT increased more markedly in responders than in nonresponders and a significant inverse relationship surfaced between plasma 5-HT and the Hamilton Rating Scale for Depression. The results support other reports of comparable antidepressant efficacy for brofaromine and phenelzine, both inhibitors of MAO-A in humans. The consistent relationship we found between the biochemical and clinical changes again suggests and supports a key role of 5-HT in the antidepressant effect of these MAO inhibitors.
mesh_terms: D000328:Adult; D000553:Ambulatory Care; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D010624:Phenelzine / Q000494:pharmacology* / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D012701:Serotonin / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C038213:brofaromine; D010624:Phenelzine