, Volume 127, Issue 1–2, pp 370–376 | Cite as

Initial monoamine oxidase-A inhibition by moclobemide does not predict the therapeutic response in patients with major depression

A double blind, randomized study
  • Françoise Radat
  • Ivan Berlin
  • Odile Spreux-Varoquaux
  • Skander Elatki
  • Maurice Ferreri
  • Alain J. Puech
Original Investigation


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-dihydroxy-phenylglycol (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 wecks. 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.

Key words

Monoamine oxidase-A inhibition Treatment outcome DHPG l-dopa DOPAC HVA 5-HIAA Moclobemide Depressive patients 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders, 3rd edn revised. Washington, DCGoogle Scholar
  2. Berlin I, Zimmer R, Thiede HM, Payan C, Hergueta T, Robin L, Puech AJ (1990) Comparison of the monoamine oxidase inhibiting properties of two reversible and selective monoamine oxidase—A inhibitors moclobemide and toloxatone, and assessment of their effect on psychometric performance in healthy subjects. Br J Clin Pharmacol 30: 805–816PubMedGoogle Scholar
  3. Berlin I, Said S, Spreux-Varoquaux O, Olivares R, Launay JM, Puech AJ (1995) Monoamine oxidase A and B activities in heavy smokers. Biol Psychiatry 38: 756–761PubMedCrossRefGoogle Scholar
  4. Bresnahan DB, Pandey GN, Janicak PG, Sharma R, Boshes RA, Chang SS, Gierl BL, Davis JM (1990) MAO inhibition and clinical response in depressed patients treated with phenelzine. J Clin Psychiatry 51: 47–50PubMedGoogle Scholar
  5. Brown MJ, Monks NJ (1983) Plasma dihydroxyphenylglycol concentration: a simple, sensitive and specific index of monoamine oxidase—A activity in vivo. Br J Clin Pharmacol 15: 599PGoogle Scholar
  6. Davidson J, McLeod M, White HL (1978) Inhibition of platelet monoamine oxidase in depressed subjects treated with phenelzine. Am J Psychiatry 135: 470–472PubMedGoogle Scholar
  7. Dingemanse J, Korn A, Pfefen JP, Güntert TW (1992) Biochemical effects of high single doses of moclobemide in man: correlation with plasma concentrations. Psychopharmacology 106: S46-S48PubMedCrossRefGoogle Scholar
  8. Eisenhofer G, Goldstein DS, Stull R, Keiser HR, Sunderland T, Murphy DL, Kopin IJ (1986) Simultaneous liquid-chromatographic determination of 3,4-dihydroxyphenylglycol, catecholamines, and 3,4-dihydroxyphenylalanine in plasma, and their response to inhibition of monoamine oxidase. Clin Chem 32: 2030–2033PubMedGoogle Scholar
  9. Eisenhofer G, Goldstein DS, Ropchak TG, Nguyen HQ, Keiser HR, Kopin IJ (1988) Source and physiological significance of plasma 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol. J Auton Nerv Syst 24: 1–14PubMedCrossRefGoogle Scholar
  10. Eisenhofer G, Bush JE, Cannon RI, Stull R, Kopin IJ, Goldstein DS (1989) Plasma dihydroxyphenylalanine and total body and regional noradrenergic activity in humans. J Clin Endocrinol Metab 68: 247–255PubMedCrossRefGoogle Scholar
  11. Eisenhofer G, Pecorella W, Pacak K, Hooper D, Kopin IJ, Goldstein DS (1994) The neuronal and extraneuronal origins of plasma 3-methoxy-4-hydroxyphenylglycol in rats. J Auton Nerv Syst 50: 93–107PubMedCrossRefGoogle Scholar
  12. Finberg JPM, Pacak K, Kopin IJ, Goldstein DS (1993) Chronic inhibition of monoamine oxidase type A increases noradrena-line release in rat frontal cortex. Naunyn-Schmiedeberg’s Arch Pharmacol 347: 500–505CrossRefGoogle Scholar
  13. Freeman H (1993) Moclobemide. Lancet 342: 1528–1532PubMedCrossRefGoogle Scholar
  14. Fritze J, Laux G, Sofic E, Koronakis P, Schoerlin MP, Riederer P, Beckmann H (1989) Plasma moclobernide and metabolites: lack of correlation with clinical response and biogenic amines. Psychopharmacology 99: 252–256PubMedCrossRefGoogle Scholar
  15. Haefely W, Burkard WP, Cesura AM, Kettler R, Lorez HP, Martin JR, Richards JG, Scherschlicht R, Da Prada M (1992) Biochemistry and pharmacology of moclobemide, a prototype RIMA. Psychopharmacology 106: S6-S14PubMedCrossRefGoogle Scholar
  16. Kopin IJ (1985) Catecholamine metabolism: basic aspects and clinical significance. Pharmacol Rev 37: 333–364PubMedGoogle Scholar
  17. Koulu M, Scheinin M, Kaarttinen A, Kallio J, Pyykkö K, Vuorinen J, Zimmer RH (1989) Inhibition of monoamine oxidase by moclobemide: effects on monoamine, metabolism and secretion of anterior pituitary hormones and cortisol in healthy volunteers. Br J Clin Pharmacol 27: 243–255PubMedGoogle Scholar
  18. Lecrubier Y, Guelfi JD (1990) Efficacy of reversible inhibitors of monoamine oxidase-A in various forms of depression. Acta Psychiatr Scand Suppl 360: 18–23PubMedCrossRefGoogle Scholar
  19. Maier W, Philipp M, Buller R, Schlegel S (1987) Reliability and validity of the Newcastle Scale in relation to ICD-9 classification. Acta Psychiatr Scand 76: 619–627PubMedCrossRefGoogle Scholar
  20. Montgomery SA, Asberg M (1979) A new depression scale designed to be sensitive to change. Br J Psychiatry 134: 382–389PubMedCrossRefGoogle Scholar
  21. Patat A, Berlin I, Durrieu G, Armand P, Fitoussi S, Molinier P, Caille P (1995) Pressor effect of oral tyramine during treatment with befloxatone, a new reversible monoamine oxidase-A inhibitor, in healthy subjects. J Clin Pharmacol 35: 633–643PubMedGoogle Scholar
  22. Ravaris CL, Nies A, Robinson DS, Ives JO, Lamborne KR, Korson L (1976) A multiple-dose, controlled study of phenelzine in depression-anxiety states. Arch Gen Psychiatry 33: 347–350PubMedGoogle Scholar
  23. Risby ED, Hsiao JK, Sunderland T, Agren H, Rudorfer MV, Potter WZ (1987) The effects of antidepressants on the cerebrospinal fluid homovalillic acid/5-hydroxyindolacetic acid ratio. Clin Pharmacol Ther 42: 547–554PubMedCrossRefGoogle Scholar
  24. Youdim MBH, Finberg JPM, Kuhn DM, Wolf WA (1984) The role of monoamine oxidase A in the metabolism and function of noradrenaline and serotonin. In: Paton W et al. (eds) IUPHA 9th International Congress of Pharmacology, Proceedings. MacMillan Press, London 2: 203–209Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Françoise Radat
    • 1
  • Ivan Berlin
    • 1
  • Odile Spreux-Varoquaux
    • 3
  • Skander Elatki
    • 1
  • Maurice Ferreri
    • 1
  • Alain J. Puech
    • 2
  1. 1.Department of PsychiatryHôpital Saint AntoineParisFrance
  2. 2.Department of Clinical PharmacologyHôpital Pitié-SalpêtrièreParisFrance
  3. 3.Department of Biochemistry, Pharmacology and ToxicologyCentre Hospitalier de VersaillesVersaillesFrance

Personalised recommendations