Sheng-Yu Lee1,2,3,4, Tzu-Yun Wang4, Shiou-Lan Chen5, Yun-Hsuan Chang6, Po-See Chen4, San-Yuan Huang7, Nian-Sheng Tzeng7, Liang-Jen Wang8, I Hui Lee4, Kao Ching Chen4, Yen Kuang Yang4, Jau-Shyong Hong9, Ru-Band Lu4,10,11,12. 1. Department of Psychiatry , Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. 2. Department of Psychiatry , School of Medicine, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 3. Department of Psychiatry , College of Medicine, National Yang-Ming University, Taipei, Taiwan. 4. Department of Psychiatry , College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan. 5. Department of Neurology , School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 6. Department of Psychology , College of Medical and Health Science, Asia University, Taichung, Taiwan. 7. Department of Psychiatry , Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. 8. Department of Child and Adolescent Psychiatry , Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan. 9. Laboratory of Toxicology and Pharmacology , NIH/NIEHS, Research Triangle Park, North Carolina. 10. Addiction Research Center , National Cheng Kung University, Tainan, Taiwan. 11. Beijing YiNing Hospital , Beijing, China. 12. Center for Neuropsychiatric Research , National Health Research Institutes, Miaoli, Taiwan.
Abstract
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.
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.
Authors: Suchitra Krishnan-Sarin; Stephanie S O'Malley; Nicholas Franco; Dana A Cavallo; Jeanette M Tetrault; Julia Shi; Ralitza Gueorguieva; Brian Pittman; John H Krystal Journal: Neuropsychopharmacology Date: 2019-10-07 Impact factor: 7.853