The catechol-O-methyltransferase Val(108/158)Met polymorphism affects antidepressant response to paroxetine in a naturalistic setting.
BACKGROUND
The noradrenergic and dopaminergic systems are targets for antidepressants and are stimulated by serotonergic antidepressant drugs. The COMT enzyme inactivates catecholamines, and the COMT Val(108/158)Met polymorphism (rs4680) influences the enzyme activity. Clinical studies on the effect of rs4680 on antidepressant response gave contrasting results.


OBJECTIVE
We studied the effect of rs4680 on response to paroxetine antidepressant monotherapy at doses administered upon clinical need.


METHODS
Fifty-five consecutively referred outpatients affected by a major depressive episode without psychotic features in course of major depressive disorder were administered paroxetine at a mean daily dose of 31.64 mg for 1 month. Changes in severity of depression were assessed with weekly Hamilton depression ratings and analyzed with repeated measures analysis of variance in the context of general linear model, taking into account potential confounding variables (age, sex, number of previous illness episodes, duration of current episode and paroxetine daily dose).


RESULTS
rs4680 significantly interacted with time in affecting antidepressant response to paroxetine, with outcome being inversely proportional to the enzyme activity: better effects in Met/Met homozygotes, worse effects in Val/Val homozygotes and intermediate effects in heterozygotes. The effect became significant at the third week of treatment. Paroxetine daily dose was proportional to baseline severity, but did not influence outcome.


CONCLUSIONS
This is the first study that reports a positive effect of rs4680 on response to selective serotonin reuptake inhibitors monotherapy in a Caucasian sample. Our findings support the hypothesis that factors affecting catecholaminergic neurotransmission might contribute to shape the individual response to antidepressants.
Benedetti
Francesco
F
Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy. benedetti.francesco@hsr.it
Colombo
Cristina
C
Pirovano
Adele
A
Marino
Elena
E
Smeraldi
Enrico
E
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D002394:Catechol O-Methyltransferase; D002395:Catecholamines; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors