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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 Val108/158Met 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. COMTVAL/VAL and COMTVAL/MET genotype carriers showed a better response than COMTMET/MET-bearing patients in the mirtazapine group. Moreover, carriers of the COMTVAL/VAL or COMTVAL/MET genotype had significantly greater HAMD-17 (Hamilton Rating Scale for Depression 17 item version) score reductions than COMTMET/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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Szegedi, A., Rujescu, D., Tadic, A. et al. The catechol-O-methyltransferase Val108/158Met polymorphism affects short-term treatment response to mirtazapine, but not to paroxetine in major depression. Pharmacogenomics J 5, 49–53 (2005). https://doi.org/10.1038/sj.tpj.6500289

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