title: The catechol-O-methyltransferase Val108/158Met polymorphism affects short-term treatment response to mirtazapine, but not to paroxetine in major depression.
abstract: The catechol-O-methyltransferase (COMT) is a major degrading enzyme in the metabolic pathways of catecholaminergic neurotransmitters such as dopamine and norepinephrine. This study investigated whether the functionally relevant Val(108/158)Met gene variant is associated with differential antidepressant response to mirtazapine and/or paroxetine in 102 patients with major depression (DSM-IV criteria) participating in a randomized clinical trial with both drugs. In patients treated with mirtazapine, but not paroxetine, allelic variations in the COMT gene were associated with differential response. COMT(VAL/VAL) and COMT(VAL/MET) genotype carriers showed a better response than COMT(MET/MET)-bearing patients in the mirtazapine group. Moreover, carriers of the COMT(VAL/VAL) or COMT(VAL/MET) genotype had significantly greater HAMD-17 (Hamilton Rating Scale for Depression 17 item version) score reductions than COMT(MET/MET) homozygotes from week 2 to 6, respectively, in the mirtazapine group. Time course of response and antidepressant efficacy of mirtazapine, but not paroxetine, seem to be influenced in a clinically relevant manner by this allelic variation within the COMT gene.
authors.affiliation: Department of Psychiatry, Charité-University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany. armin.szegedi@charite.de
authors.forename: A
authors.initials: A
authors.lastname: Szegedi
authors.forename: D
authors.initials: D
authors.lastname: Rujescu
authors.forename: A
authors.initials: A
authors.lastname: Tadic
authors.forename: M J
authors.initials: MJ
authors.lastname: Müller
authors.forename: R
authors.initials: R
authors.lastname: Kohnen
authors.forename: H H
authors.initials: HH
authors.lastname: Stassen
authors.forename: N
authors.initials: N
authors.lastname: Dahmen
mesh_terms: D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D008803:Mianserin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008875:Middle Aged; D000078785:Mirtazapine; D017374:Paroxetine / Q000627:therapeutic use*; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics*; D013997:Time Factors; D014633:Valine / Q000235:genetics
chemical_list: D008803:Mianserin; D017374:Paroxetine; D000078785:Mirtazapine; D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine