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

Published online by Cambridge University Press:  16 April 2020

F. Benedetti ,
S. Dallaspezia ,
C. Colombo ,
C. Lorenzi ,
A. Pirovano  and
E. Smeraldi
F. Benedetti*
Affiliation:
Department of Clinical Neurosciences, Istituto Scientifico Ospedale San Raffaele, University Vita-Salute San Raffaele, San Raffaele Turro, Via Stamira d’Ancona 20, Milano, Italy
S. Dallaspezia
Affiliation:
Department of Clinical Neurosciences, Istituto Scientifico Ospedale San Raffaele, University Vita-Salute San Raffaele, San Raffaele Turro, Via Stamira d’Ancona 20, Milano, Italy
C. Colombo
Affiliation:
Department of Clinical Neurosciences, Istituto Scientifico Ospedale San Raffaele, University Vita-Salute San Raffaele, San Raffaele Turro, Via Stamira d’Ancona 20, Milano, Italy
C. Lorenzi
Affiliation:
Department of Clinical Neurosciences, Istituto Scientifico Ospedale San Raffaele, University Vita-Salute San Raffaele, San Raffaele Turro, Via Stamira d’Ancona 20, Milano, Italy
A. Pirovano
Affiliation:
Department of Clinical Neurosciences, Istituto Scientifico Ospedale San Raffaele, University Vita-Salute San Raffaele, San Raffaele Turro, Via Stamira d’Ancona 20, Milano, Italy
E. Smeraldi
Affiliation:
Department of Clinical Neurosciences, Istituto Scientifico Ospedale San Raffaele, University Vita-Salute San Raffaele, San Raffaele Turro, Via Stamira d’Ancona 20, Milano, Italy
*
*Corresponding author. Tel.: +39 02 26433156; fax: +39 02 26433265. E-mail address: [email protected] (F. Benedetti).
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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.

Keywords

COMTSerotoninNoradrenalineDopamineAntidepressantFluvoxamine
Type
Depression
Information
European Psychiatry , Volume 25 , Issue 8 , December 2010 , pp. 476 - 478
Copyright
Copyright © Elsevier Masson SAS 2010

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References

Arias, B, Serretti, A, Lorenzi, C, Gasto, C, Catalan, R, Fananas, LAnalysis of COMT gene (Val 158 Met polymorphism) in the clinical response to SSRIs in depressive patients of European origin. J Affect Disord 2006; 90: 251–256.10.1016/j.jad.2005.11.008CrossRefGoogle ScholarPubMed
Baune, BT, Hohoff, C, Berger, K, Neumann, A, Mortensen, S, Roehrs, Tet al.Association of the COMT val158met variant with antidepressant treatment response in major depression. Neuropsychopharmacology 2008; 33: 924–932.10.1038/sj.npp.1301462CrossRefGoogle ScholarPubMed
Benedetti, F, Barbini, B, Bernasconi, A, Fulgosi, MC, Dallaspezia, S, Gavinelli, Cet al.Acute antidepressant response to sleep deprivation combined with light therapy is influenced by the catechol-O-methyltransferase Val(108/158)Met polymorphism. J Affect Disord 2010;121(1-2):68–72.CrossRefGoogle Scholar
Benedetti, F, Colombo, C, Pirovano, A, Marino, E, Smeraldi, EThe catechol-O-methyltransferase Val(108/158)Met polymorphism affects antidepressant response to paroxetine in a naturalistic setting. Psychopharmacology (Berl) 2009; 203: 155–160.10.1007/s00213-008-1381-7CrossRefGoogle Scholar
Faul, F, Erdfelder, E, Lang, AG, Buchner, AG*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 2007; 39: 175–191.CrossRefGoogle ScholarPubMed
Gerstenberg, G, Aoshima, T, Fukasawa, T, Yoshida, K, Takahashi, H, Higuchi, Het al.Relationship between clinical effects of fluvoxamine and the steady-state plasma concentrations of fluvoxamine and its major metabolite fluvoxamino acid in Japanese depressed patients. Psychopharmacology (Berl) 2003; 167: 443–448.CrossRefGoogle ScholarPubMed
Hill, T, Lewicki, PStatistics: methods and applications. A comprehensive reference for science, industry, and data mining. General Linear Models Tulsa (OK): StatSoft; 2006. 245–276 Chapter 18.Google Scholar
Kasper, S, Dotsch, M, Kick, H, Vieira, A, Moller, HJPlasma concentrations of fluvoxamine and maprotiline in major depression: implications on therapeutic efficacy and side effects. Eur Neuropsychopharmacol 1993; 3: 13–21.10.1016/0924-977X(93)90290-3CrossRefGoogle ScholarPubMed
Kobayashi, T, Hayashi, E, Shimamura, M, Kinoshita, M, Murphy, NPNeurochemical responses to antidepressants in the prefrontal cortex of mice and their efficacy in preclinical models of anxiety-like and depression-like behavior: a comparative and correlational study. Psychopharmacology (Berl) 2008; 197: 567–580.10.1007/s00213-008-1070-6CrossRefGoogle ScholarPubMed
Kugaya, A, Seneca, NM, Snyder, PJ, Williams, SA, Malison, RT, Baldwin, RMet al.Changes in human in vivo serotonin and dopamine transporter availabilities during chronic antidepressant administration. Neuropsychopharmacology 2003; 28: 413–420.CrossRefGoogle Scholar
Lachman, HM, Papolos, DF, Saito, T, Yu, YM, Szumlanski, CL, Weinshilboum, RMHuman catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 1996; 6: 243–250.10.1097/00008571-199606000-00007CrossRefGoogle ScholarPubMed
Lucca, A, Lucini, V, Catalano, M, Alfano, M, Smeraldi, EPlasma tryptophan to large neutral amino acids ratio and therapeutic response to a selective serotonin uptake inhibitor. Neuropsychobiology 1994; 29: 108–111.CrossRefGoogle ScholarPubMed
McCulloch, CE, Searle, SR, Neuhaus, JMGeneralized Linear and Mixed Models. 2nd Ed. John Wiley & Sons. 2008.Google Scholar
Millan, MJMulti-target strategies for the improved treatment of depressive states: Conceptual foundations and neuronal substrates, drug discovery and therapeutic application. Pharmacol Ther 2006; 110: 135–370.CrossRefGoogle ScholarPubMed
Muller, KE, LaVange, LM, Ramey, SL, Ramey, CTPower calculations for general linear multivariate models including repeated measures applications. J Am Stat Assoc 1992; 87: 1209–1226.10.1080/01621459.1992.10476281CrossRefGoogle ScholarPubMed
O’Brien, RG, Muller, KEA unified approach to statistical power for t-tests to multivariate models. Edwards, LK, Applied analysis of variance in behavioral sciences New York: Marcel Dekker; 1992.Google Scholar
Perlis, RH, Fijal, B, Adams, DH, Sutton, VK, Trivedi, MH, Houston, JPVariation in catechol-O-methyltransferase is associated with duloxetine response in a clinical trial for major depressive disorder. Biol Psychiatry 2009; 65: 785–791.10.1016/j.biopsych.2008.10.002CrossRefGoogle Scholar
Smeraldi, E, Zanardi, R, Benedetti, F, Dibella, D, Perez, J, Catalano, MPolymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. Mol Psychiatry 1998; 3: 508–511.CrossRefGoogle ScholarPubMed
Smolders, I, Clinckers, R, Meurs, A, De Bundel, D, Portelli, J, Ebinger, Get al.Direct enhancement of hippocampal dopamine or serotonin levels as a pharmacodynamic measure of combined antidepressant-anticonvulsant action. Neuropharmacology 2008; 54: 1017–1028.10.1016/j.neuropharm.2008.02.006CrossRefGoogle ScholarPubMed
Sulzer, D, Edwards, RHAntidepressants and the monoamine masquerade. Neuron 2005; 46: 1–2.CrossRefGoogle ScholarPubMed
Szegedi, A, Rujescu, D, Tadic, A, Muller, MJ, Kohnen, R, Stassen, HHet al.The catechol-O-methyltransferase Val108/158Met polymorphism affects short-term treatment response to mirtazapine, but not to paroxetine in major depression. Pharmacogenomics J 2005; 5: 49–53.10.1038/sj.tpj.6500289CrossRefGoogle Scholar
Timm, N, Kim, KUnivariate and Multivariate General Linear Models: Theory and Applications with SAS. 2nd Ed. Berlin: Heidelberg Springer; 2006. Hall/CRC. C, editorGoogle Scholar
Tremblay, P, Blier, PCatecholaminergic strategies for the treatment of major depression. Curr Drug Targets 2006; 7: 149–158.CrossRefGoogle ScholarPubMed
Tsai, SJ, Gau, YT, Hong, CJ, Liou, YJ, Yu, YW, TJ, CSexually dimorphic effect of catechol-O-methyltransferase val158met polymorphism on clinical response to fluoxetine in major depressive patients. J Affect Disord 2008; 113: 183–187.CrossRefGoogle ScholarPubMed
Yoshida, K, Higuchi, H, Takahashi, H, Kamata, M, Sato, K, Inoue, Ket al.Influence of the tyrosine hydroxylase val81met polymorphism and catechol-O-methyltransferase val158met polymorphism on the antidepressant effect of milnacipran. Hum Psychopharmacol 2008; 23: 121–128.CrossRefGoogle ScholarPubMed
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