The catechol-O-methyltransferase Val(108/158)Met polymorphism affects short-term treatment response to mirtazapine, but not to paroxetine in major depression

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. 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.