Anti-inflammation and neuroprotective drugs benefit the treatment of bipolar II disorder patients

L dose memantine might possess anti-inflammatory and neuroprotective effects mechanistically remote from the NMDA receptor. We investigated whether using valproic acid (VPA) add-on memantine (5 mg/day) to treat bipolar II disorder (BP-II) is more effective than using VPA alone. In this randomized, double-blind, controlled 12 week study, BP-II patients were randomly assigned to a group: VPA+Memantine or VPA+Placebo (Pbo). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical response, alone with plasma levels of tumor necrosis factor (TNF-α), interleukin 6 (IL-6), IL-8, and IL-1and metabolic profiles during week 0, 1, 2, 4, 8 and 12.After 12 weeks, there was a significant increase of high-density lipoprotein cholesterol (HDL-C) (p<0.009) in the memantine group compared with the Pbo group. The TNF-α were significantly decreased in the memantine group than in the Pbo group (P=0.013).The changes in HDRS score were significantly associated with changes in IL-6 (P=0.012) and IL-1(P=0.005) levels; changes in YMRS score associated with changes with TNF-α(P=0.005) level changes.The association between BDNF Val66Met polymorphism with treatment response was evaluated. After stratified by 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 memantine might benefit treatment of BP-II via decreasing cytokines and increasing HDL-C. The BDNF Val66Met polymorphism influences responses to add-on memantine by decreasing depressive symptoms in BP-II.