Influence of the tyrosine hydroxylase val81met polymorphism and catechol-O-methyltransferase val158met polymorphism on the antidepressant effect of milnacipran.
OBJECTIVE
Genetic polymorphisms of the noradrenergic pathway can be factors to predict the effect of antidepressants when their pharmacological mechanisms of action include the noradrenergic system. The purpose of the present study was to determine whether the tyrosine hydroxylase (TH) val81met and catechol-O-methyltransferase (COMT) val158met polymorphisms are associated with the antidepressant effect of milnacipran, a serotonin/noradrenaline reuptake inhibitor.


METHODS
Eighty-one Japanese patients with major depressive disorder were treated with milnacipran for 6 weeks. Severity of depression was assessed with the Montgomery and Asberg Depression Rating Scale (MADRS). Assessments were carried out at baseline and at 1, 2, 4 and 6 weeks of treatment. The method of polymerase chain reaction was used to determine allelic variants.


RESULTS
The met/met genotype of the COMT val158met polymorphism was associated with a significantly faster therapeutic effect of milnacipran in the MADRS score during this study. No influence of the TH val81met polymorphism on the antidepressant effect of milnacipran was detected.


CONCLUSIONS
These results suggest that the COMT val158met polymorphism in part determines the antidepressant effect of milnacipran.
Yoshida
Keizo
K
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan. cxw01076@nifty.com
Higuchi
Hisashi
H
Takahashi
Hitoshi
H
Kamata
Mitsuhiro
M
Sato
Kazuhiro
K
Inoue
Kazuyuki
K
Suzuki
Toshio
T
Itoh
Kunihiko
K
Ozaki
Norio
N
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000483:Alleles; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D044466:Asian People; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D003521:Cyclopropanes / Q000494:pharmacology* / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D000078764:Milnacipran; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012720:Severity of Illness Index; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics* / Q000378:metabolism
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D002394:Catechol O-Methyltransferase; D003521:Cyclopropanes; D000078764:Milnacipran; D017367:Selective Serotonin Reuptake Inhibitors; D014446:Tyrosine 3-Monooxygenase