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J Psychiatr Res. 2013 Oct;47(10):1343-8. doi: 10.1016/j.jpsychires.2013.06.017. Epub 2013 Jul 18.

Add-on memantine to valproate treatment increased HDL-C in bipolar II disorder.

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Department of Psychiatry, National Cheng Kung University, Tainan, Taiwan.


Memantine is a noncompetitive NMDA receptor antagonist. As an augmenting agent, it has an antidepressant-like and mood-stabilizing effect. Memantine also reduces binge eating episodes and weight. We investigated whether memantine added on to valproate (VPA) is more effective than VPA alone for treating BP-II depression and improving the patient's metabolic profile. This was a randomized, double-blind, controlled study. BP-II patients undergoing regular VPA treatments were randomly assigned to one of two groups: VPA plus either add-on [1] memantine (5 mg/day) (n = 62) or [2] placebo (n = 73) for 12 weeks. The Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS) were used to evaluate clinical response. Height, weight, fasting serum glucose, fasting total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides were followed regularly. Multiple linear regressions with generalized estimating equation methods were used to analyze the effects of memantine on clinical performance. There were no significant differences in pre- and post-treatment YMRS and HDRS scores between the VPA + memantine and VPA + placebo groups. Although there were no significant differences in the pre- and post-treatment values of most metabolic indices between the two groups, there was a significant increase of HDL-C (p = 0.009) in the VPA + memantine group compared with the VPA + placebo group. This increase remained significant even after controlling for body mass index (BMI) (p = 0.020). We conclude that add-on memantine plus VPA treatment of BP-II depression increases the blood level of HDL-C even in the absence of change in affective symptoms.


NCT01188148 (, Trial date was from 1st August, 2008 to 31st July, 2012 in National Cheng Kung University and Tri-Service General Hospital.


Bipolar II disorder; HDL-C; Memantine; Treatment

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