PMID- 25262178 OWN - NLM STAT- MEDLINE DCOM- 20150929 LR - 20151119 IS - 1873-7862 (Electronic) IS - 0924-977X (Linking) VI - 24 IP - 11 DP - 2014 Nov TI - Therapeutic effects of add-on low-dose dextromethorphan plus valproic acid in bipolar disorder. PG - 1753-9 LID - S0924-977X(14)00252-1 [pii] LID - 10.1016/j.euroneuro.2014.09.001 [doi] AB - 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. CI - Copyright (c) 2014 Elsevier B.V. and ECNP. All rights reserved. FAU - Chen, Shiou-Lan AU - Chen SL AD - Department of Neurology, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Lee, Sheng-Yu AU - Lee SY AD - Department of Psychiatry, Kaohsiung Veteran׳s General Hospital, Kaohsiung, Taiwan. FAU - Chang, Yun-Hsuan AU - Chang YH AD - Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; Addiction Research Center, National Cheng Kung University, Tainan, Taiwan. FAU - Chen, Po-See AU - Chen PS AD - Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. FAU - Lee, I-Hui AU - Lee IH AD - Department of Neurology, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Behavioral Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Wang, Tzu-Yun AU - Wang TY AD - Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. FAU - Chen, Kao-Ching AU - Chen KC AD - Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. FAU - Yang, Yen-Kuang AU - Yang YK AD - Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; Addiction Research Center, National Cheng Kung University, Tainan, Taiwan. FAU - Hong, Jau-Shyong AU - Hong JS AD - Laboratory of Toxicology and Pharmacology, NIH/NIEHS, Research Triangle Park, NC, USA. FAU - Lu, Ru-Band AU - Lu RB AD - Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Behavioral Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Addiction Research Center, National Cheng Kung University, Tainan, Taiwan; Center for Neuropsychiatric Research, National Health Research Institute, Miaoli, Taiwan. Electronic address: rblu@mail.ncku.edu.tw. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20140916 PL - Netherlands TA - Eur Neuropsychopharmacol JT - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JID - 9111390 RN - 0 (Antimanic Agents) RN - 0 (Biomarkers) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cytokines) RN - 0 (Neuroprotective Agents) RN - 614OI1Z5WI (Valproic Acid) RN - 7355X3ROTS (Dextromethorphan) SB - IM MH - Adult MH - Antimanic Agents/therapeutic use MH - Biomarkers/blood MH - Bipolar Disorder/blood/*drug therapy MH - Brain-Derived Neurotrophic Factor/blood MH - Cytokines/*blood MH - Dextromethorphan/*administration & dosage/*therapeutic use MH - Double-Blind Method MH - Drug Therapy, Combination MH - Female MH - Humans MH - Male MH - Neuroprotective Agents/therapeutic use MH - Psychiatric Status Rating Scales MH - Treatment Outcome MH - Valproic Acid/*administration & dosage/*therapeutic use MH - Young Adult OTO - NOTNLM OT - BDNF OT - Bipolar disorder OT - Cytokine OT - HDRS OT - YMRS EDAT- 2014/09/30 06:00 MHDA- 2015/09/30 06:00 CRDT- 2014/09/29 06:00 PHST- 2014/04/30 00:00 [received] PHST- 2014/08/08 00:00 [revised] PHST- 2014/09/03 00:00 [accepted] PHST- 2014/09/29 06:00 [entrez] PHST- 2014/09/30 06:00 [pubmed] PHST- 2015/09/30 06:00 [medline] AID - S0924-977X(14)00252-1 [pii] AID - 10.1016/j.euroneuro.2014.09.001 [doi] PST - ppublish SO - Eur Neuropsychopharmacol. 2014 Nov;24(11):1753-9. doi: 10.1016/j.euroneuro.2014.09.001. Epub 2014 Sep 16.