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

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

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1753-1759
Number of pages7
JournalEuropean Neuropsychopharmacology
Issue number11
Publication statusPublished - 2014 Nov 1

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)


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