Influence of serotonergic/noradrenergic gene polymorphisms on nausea and sweating induced by milnacipran in the treatment of depression

Abstract

Hisashi Higuchi1, Hitoshi Takahashi2, Mitsuhiro Kamata3, Keizo Yoshida41Department of Psychiatry, St. Marianna University, School of Medicine, Kanagawa, Japan; 2Department of Psychiatry, Tokyo Women’s Medical University, School of Medicine, Tokyo, Japan; 3Department of Psychiatry, Yuri-Kumiai General Hospital, Yuri-Honjo, Akita, Japan; 4Department of Psychiatry, Nagoya University School of Medicine, Aichi, JapanAbstract: The present study was conducted to find out the predictors of side effects such as nausea and excessive sweating induced by milnacipran, a serotonin/norepinephrine reuptake inhibitor. Both clinical characteristics prior to the treatment and gene polymorphisms such as serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR), a variable number of tandem repeats in the second intron of the 5-HTT gene (5-HTTVNTR), 5-HT2A receptor gene (5-HT2A G-1438A), a TPH gene polymorphism in intron 7 (TPH A218C), norepinephrine transporter (NET) gene polymorphism in the promoter region (NET T-182C) and in the exon 9 (NET G1287A), a variable number of tandem repeats in the promoter region of monoamine oxidase A, were items to be assessed in this study. Ninety-six patients with major depressive disorder were treated with milnacipran. Side effects were assessed at 1, 2, 4, and 6 weeks of treatment with Udvalg for Kliniske Undersogelser side effects scale. The results showed that no gene polymorphisms included in this study affected the susceptibility of nausea and excessive sweating induced by milnacipran. Patients with older age are more likely to develop excessive sweating than others. The major limitation of this study is a small sample size. Further studies with larger populations and more kinds of gene polymorphisms should be needed to see if specific gene polymorphisms determine the susceptibility of side effects induced by milnacipran. Keywords: milnacipran, nausea, excessive sweating, gene polymorphisms