Prediction of antidepressant response to milnacipran by norepinephrine transporter gene polymorphisms.
OBJECTIVE
With a multitude of antidepressants available, predictors of response to different classes of antidepressants are of considerable interest. The purpose of the present study was to determine whether norepinephrine transporter gene (NET) and serotonin transporter gene (5-HTT) polymorphisms are associated with the antidepressant response to milnacipran, a dual serotonin/norepinephrine reuptake inhibitor.


METHODS
Ninety-six Japanese patients with major depressive disorder were treated with milnacipran, 50-100 mg/day, for 6 weeks. Severity of depression was assessed with the Montgomery-Asberg Depression Rating Scale. 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
Eighty patients completed the study. The presence of the T allele of the NET T-182C polymorphism was associated with a superior antidepressant response, whereas the A/A genotype of the NET G1287A polymorphism was associated with a slower onset of therapeutic response. In contrast, no influence of 5-HTT polymorphisms on the antidepressant response to milnacipran was detected.


CONCLUSIONS
The results suggest that NET but not 5-HTT polymorphisms in part determine the antidepressant response to milnacipran.
Yoshida
Keizo
K
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, USA. cxw01076@nifty.com
Takahashi
Hitoshi
H
Higuchi
Hisashi
H
Kamata
Mitsuhiro
M
Ito
Ken-ichi
K
Sato
Kazuhiro
K
Naito
Shingo
S
Shimizu
Tetsuo
T
Itoh
Kunihiko
K
Inoue
Kazuyuki
K
Suzuki
Toshio
T
Nemeroff
Charles B
CB
D018759:Adrenergic Uptake Inhibitors / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000235:genetics; D003521:Cyclopropanes / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins; D008875:Middle Aged; D000078764:Milnacipran; D009419:Nerve Tissue Proteins / Q000235:genetics; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use*; D027981:Symporters / Q000235:genetics*; D016896:Treatment Outcome
D018759:Adrenergic Uptake Inhibitors; D002352:Carrier Proteins; D003521:Cyclopropanes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D000078764:Milnacipran; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D044402:Receptor, Serotonin, 5-HT2A; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D027981:Symporters; C493227:SLC6A2 protein, human; C493230:SLC6A4 protein, human