1. ¹Department of Psychiatry, Charité-University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany
2. ²Department of Psychiatry, University of Munich, Germany
3. ³Department of Psychiatry, University of Mainz, Germany
4. ⁴IMEREM, Nürnberg, Germany
5. ⁵Department of Psychiatry, University of Zürich, Switzerland

Correspondence: Professor A Szegedi, Department of Psychiatry, Charité-University Medicine Berlin, Campus Benjamin Franklin, Eschenallee 3, Berlin D-14050, Germany. Tel: +49 30 8445 8779; Fax: +49 30 8445 8341; E-mail: armin.szegedi@charite.de

Received 18 March 2004; Revised 17 September 2004; Accepted 27 September 2004; Published online 2 November 2004.

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^108/158Met 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. 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.