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Journal of Psychopharmacology
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0269881106072192v1
21/6/650    most recent
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Article

The G196A polymorphism of the brain-derived neurotrophic factor gene and the antidepressant effect of milnacipran and fluvoxamine

Keizo Yoshida1*, Hisashi Higuchi2, Mitsuhiro Kamata3, Hitoshi Takahashi4, Kazuyuki Inoue5, Toshio Suzuki5, Kunihiko Itoh6, Norio Ozaki1

1 Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
2 Omagari City Hospital, Akita, Japan.
3 Yuri Kumiai General Hospital, Akita, Japan.
4 Yokote Kohsei Hospital, Akita, Japan.
5 Department of Pharmaceutical Science, Akita University Hospital, Akita, Japan.
6 Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.

* To whom correspondence should be addressed.


  Abstract

Prediction of the response to different classes of antidepressants has been an important matter of concern in the field of psychopharmacology. The purpose of the present study was to investigate whether the G196A polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with the antidepressant effect of milnacipran, a serotonin norepinephrine reuptake inhibitor, and fluvoxamine, a selective serotonin reuptake inhibitor. The subjects of our previous study of milnacipran (n = 80) and fluvoxamine (n = 54) were included in the present study. Severity of depression was assessed with the Montgomery Åsberg depression rating scale (MADRS). Assessments were carried out at baseline and at 1, 2, 4 and 6 weeks of treatment. Polymerase chain reaction was used to determine allelic variants. In all subjects receiving milnacipran or fluvoxamine, the G/A genotype of the BDNF G196A polymorphism was associated with a significantly better therapeutic effect in the MADRS scores during this study. When milnacipran and fluvoxamine-treated subjects were analysed independently, the G/A genotype group showed greater reduction of MADRS scores than other genotype groups, irrespective of which antidepressant was administered. These results suggest that the BDNF G196A polymorphism in part determines the antidepressant effect of both milnacipran and fluvoxamine.

Key Words: antidepressant effect, genetic polymorphism, fluvoxamine, major depressive disorder, milnacipran

First published on November 8, 2006, doi:10.1177/0269881106072192

Journal of Psychopharmacology 2007;21:650.

A more recent version of this article appeared on August 1, 2007

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