Add-On Memantine Treatment for Bipolar II Disorder Comorbid with Alcohol Dependence: A 12-Week Follow-Up Study

Sheng Yu Lee, Tzu Yun Wang, Shiou Lan Chen, Yun Hsuan Chang, Po See Chen, San Yuan Huang, Nian Sheng Tzeng, Liang Jen Wang, I. Hui Lee, Kao Ching Chen, Yen Kuang Yang, Jau Shyong Hong, Ru Band Lu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

9 Scopus citations


Background: Bipolar disorder (BD), especially BD-II, is frequently comorbid with alcohol dependence. Because BD-II and alcohol dependence are neurodegenerative disorders, agents with anti-inflammatory and neurotrophic effects might provide effective therapy. We investigated whether add-on memantine to regular valproic acid treatment ameliorated clinical symptoms, reduced alcohol use, and cytokine levels, and increased plasma brain-derived neurotrophic factor (BDNF) in BD-II patients with comorbid alcohol dependence. Methods: In a single-arm 12-week clinical trial, BD-II patients with comorbid alcohol dependence (n = 45) undergoing regular valproic acid treatments were given add-on memantine (5 mg/d). Symptom severity, alcohol use, cytokine (plasma tumor necrosis factor-α and C-reactive protein [CRP], transforming growth factor-β1 [TGF-β1], interleukin-8 [IL-8], IL-10), and plasma BDNF levels were regularly assessed. Results: Mean within-group decreases in Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) scores, alcohol use, CRP, BDNF, and IL-8 levels were significantly different from baseline after 12 weeks of treatment. We found no significant correlation between alcohol use levels and changes in HDRS or YMRS scores. The correlation between reduced alcohol use and reduced TGF-β1 level was significant (B = 0.003, p = 0.019). Conclusions: BD-II comorbid with alcohol dependence might benefit from add-on memantine treatment, which significantly reduced clinical severity, alcohol use, and plasma cytokine levels, and increased BDNF levels.

Original languageEnglish
Pages (from-to)1044-1050
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Issue number6
StatePublished - 06 2018

Bibliographical note

Publisher Copyright:
Copyright © 2018 by the Research Society on Alcoholism


  • Alcohol Dependence
  • BDNF
  • Bipolar II Disorder
  • Cytokines
  • Memantine


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