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Pharmacogenomics J. 2005;5(1):49-53.

The catechol-O-methyltransferase Val108/158Met polymorphism affects short-term treatment response to mirtazapine, but not to paroxetine in major depression.

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Department of Psychiatry, Charité-University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.


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.

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