Effect of catechol-O-methyltransferase Val(108/158)Met polymorphism on antidepressant efficacy of fluvoxamine

F. Benedetti, S. Dallaspezia, C. Colombo, C. Lorenzi, A. Pirovano, E. Smeraldi

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Rationale: The catechol-O-methyltransferase (COMT) enzyme inactivates catecholamines, and the COMT Val(108/158)Met polymorphism (rs4680) influences the enzyme activity. Recent clinical studies found a significant effect of rs4680 on antidepressant response to fluoxetine and paroxetine, but several other studies were negative. No study considered drug plasma levels as possible nuisance covariate. Objectives: We studied the effect of rs4680 on response to fluvoxamine antidepressant monotherapy. Patients and methods: Forty-one consecutively admitted inpatients affected by a major depressive episode in course of major depressive disorder were administered fluvoxamine for 6 weeks. Changes in severity of depression were assessed with weekly Hamilton Depression ratings and analyzed with repeated measures ANOVA in the context of General Linear Model, with rs4680 and fluvoxamine plasma levels as factors. Results: rs4680 significantly interacted with time in affecting antidepressant response to fluvoxamine, with outcome being inversely proportional to the enzyme activity: better effects in Met-carriers, worse effects in Val/Val homozygotes. The effect became significant at the fourth week of treatment, and influence final response rates. Fluvoxamine plasma levels had marginal effects on outcome. Conclusions: This is the first study that reports a positive effect of rs4680 on response to fluvoxamine, and the third independent report of its influence on response to selective 5-HT reuptake inhibitors (SSRIs). Our findings support the hypothesis that factors affecting catecholaminergic neurotransmission might contribute to shape the individual response to antidepressants irrespective of their primary molecular target.

Original languageEnglish
Pages (from-to)476-478
Number of pages3
JournalEuropean Psychiatry
Volume25
Issue number8
DOIs
Publication statusPublished - Dec 2010

Fingerprint

Fluvoxamine
Catechol O-Methyltransferase
Antidepressive Agents
Enzymes
Depression
Paroxetine
Fluoxetine
Major Depressive Disorder
Homozygote
Synaptic Transmission
Catecholamines
Inpatients
Linear Models
Serotonin
Analysis of Variance
Pharmaceutical Preparations

Keywords

  • Antidepressant
  • COMT
  • Dopamine
  • Fluvoxamine
  • Noradrenaline
  • Serotonin

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Effect of catechol-O-methyltransferase Val(108/158)Met polymorphism on antidepressant efficacy of fluvoxamine. / Benedetti, F.; Dallaspezia, S.; Colombo, C.; Lorenzi, C.; Pirovano, A.; Smeraldi, E.

In: European Psychiatry, Vol. 25, No. 8, 12.2010, p. 476-478.

Research output: Contribution to journalArticle

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