Therapeutic effects of add-on low-dose dextromethorphan plus valproic acid in bipolar disorder.

Abstract

UNLABELLED:

Changes in inflammatory cytokines and dysfunction of the neurotrophic system are thought to be involved in the pathology of bipolar disorder (BP). We investigated whether inflammatory and neurotrophic factors were changed in BP. We also investigated whether treating BP with valproic acid (VPA) plus low-dose (30 or 60 mg/day) dextromethorphan (DM) is more effective than treating it with VPA only, and whether DM affects plasma cytokines and brain derived neurotrophic factor (BDNF) levels. In a 12-week, randomized, double-blind study, patients were randomly assigned to the VPA+DM30, VPA+DM60, or VPA+Placebo groups. The Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS) were used to evaluate symptom severity, and ELISA to analyze plasma cytokine and BDNF levels. We recruited 309 patients with BP and 123 healthy controls. Before treatment, patients with BP had significantly higher plasma cytokine and lower plasma BDNF levels than did healthy controls. After treatment, HDRS and YMRS scores in each group showed significant improvement. Plasma cytokine levels tended to decline in all groups. Changes in plasma BDNF levels were significantly greater in the VPA+DM60 group than in the VPA+Placebo group.

CONCLUSION:

patients with BP have a certain degree of systemic inflammation and BDNF dysfunction. Treatment with VPA plus DM (60 mg/day) provided patients with BP significantly more neurotrophic benefit than did VPA treatment alone.

• Authors: Shiou-Lan Chen, Sheng-Yu Lee, Yun-Hsuan Chang, Po-See Chen, I-Hui Lee, Tzu-Yun Wang, Kao-Ching Chen, Yen-Kuang Yang, Jau-Shyong Hong, Ru-Band Lu
• Journal: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology (Eur Neuropsychopharmacol) Vol. 24 Issue 11 Pg. 1753-9 (Nov 2014) ISSN: 1873-7862 [Electronic] Netherlands
• PMID: 25262178 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Chemical References

• Antimanic Agents
• Biomarkers
• Brain-Derived Neurotrophic Factor
• Cytokines
• Neuroprotective Agents
• Valproic Acid
• Dextromethorphan

Topics

• Adult
• Antimanic Agents (therapeutic use)
• Biomarkers (blood)
• Bipolar Disorder (blood, drug therapy)
• Brain-Derived Neurotrophic Factor (blood)
• Cytokines (blood)
• Dextromethorphan (administration & dosage, therapeutic use)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Male
• Neuroprotective Agents (therapeutic use)
• Psychiatric Status Rating Scales
• Treatment Outcome
• Valproic Acid (administration & dosage, therapeutic use)
• Young Adult