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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].

Page last updated: 2014-11-30

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