Genotype variant associated with add-on memantine in bipolar II disorder.
Author(s): Lee SY(1), Chen SL(1), Chang YH(1), Chen SH(1), Chu CH(1), Huang SY(2), Tzeng
NS(2), Wang CL(1), Wang LJ(3), Lee IH(1), Yeh TL(1), Yang YK(4), Hong JS(1), Lu
RB(1).
Affiliation(s): Author information:
(1)Department of Psychiatry, National Cheng Kung University, Tainan, Taiwan.
(2)Department of Psychiatry, Tri-Service General Hospital, National Defence Medical
Centre, Taipei, Taiwan.
(3)Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial
Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
(4)Institute of Behavioural Medicine, National Cheng Kung University, Tainan,
Taiwan.
Publication date & source: 2014, Int J Neuropsychopharmacol. , 17(2):189-97
Memantine is a non-competitive N-methyl-d-asparate (NMDA) receptor antagonist
with a mood-stabilizing effect. We investigated whether using valproic acid (VPA)
plus add-on memantine to treat bipolar II disorder (BP-II) is more effective than
using VPA alone (VPA + Pbo). We also evaluated, in BP-II patients, the
association between the brain-derived neurotrophic factor (BDNF) Val66Met
polymorphism with treatment response to VPA + add-on memantine and to VPA + Pbo.
In this randomized, double-blind, controlled 12 wk study, BP-II patients
undergoing regular VPA treatments were randomly assigned to a group:
VPA + Memantine (5 mg/day) (n = 115) or VPA + Pbo (n = 117). The Hamilton
Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to
evaluate clinical response during week 0, 1, 2, 4, 8 and 12. The genotypes of the
BDNF Val66Met polymorphisms were determined using polymerase chain reactions plus
restriction fragment length polymorphism analysis. To adjust within-subject
dependence over repeated assessments, multiple linear regression with generalized
estimating equation methods was used to analyze the effects of the BDNF Val66Met
polymorphism on the clinical performance of memantine. Both groups showed
significantly decreased YMRS and HDRS scores after 12 wk of treatment; the
differences between groups were non-significant. When stratified by the BDNF
Val66Met genotypes, significantly greater decreases in HDRS scores were found in
the VPA + memantine group in patients with the Val Met genotype (p = 0.004). We
conclude that the BDNF Val66Met polymorphism influenced responses to add-on
memantine by decreasing depressive symptoms in patients with BP-II.
Erratum in
Int J Neuropsychopharmacol. 2014 Jun;17(6):979. Lu, Ru-Band [removed]; Hong,
Jau-Shyong [added].
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