Dextromethorphan protect the valproic acid induced downregulation of neutrophils in patients with bipolar disorder
Ru Band Lu 3, Yun-Hsuan Chang 4, 5, Sheng-Yu Lee 6, Tzu-Yun Wang 3, Shu-Li Cheng 7, Po-See Chen 3, Yen-Kuang Yang 3, Jau-Shyong Hong 8, Shiou Lan Chen 1, 2, 3*
1Graduate Institute of Medicine & M.Sc. Program in Tropical Medicine, College of Medicine, Kaohsiung Medical University (KMU), Kaohsiung, Taiwan, ROC., 2Department of Medical Research, KMU Hospital, Kaohsiung, Taiwan, ROC., 3Department of Psychiatry, National Cheng Kung University Hospital, Tainan, Taiwan, ROC., 4Department of Psychology, Asia University, Taichung, Taiwan, ROC., 5Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, ROC., 6Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC., 7Dpartment of Nursing, Mackay Medical College, Taipei, Taiwan, ROC., 8Neurobiology Laboratory, NIH/NIEHS, Research Triangle Park, NC, USA.
Received: July 8, 2019; Revised: August 30, 2019; Accepted: October 24, 2019; Published online: October 24, 2019.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Abstract
Objective: Valproic acid (VPA) is an anticonvulsant and commonly long term used as a mood stabilizer for patients with mood disorders. However its chronic effects on the hematological changes were noticed and need to be further evaluated. In this study, we evaluated, in Taiwanese Han Chinese patients with bipolar disorders (BD), the chronic effects of VPA or VPA plus dextromethorphan (DM) on the hematological molecules (white blood cell [WBCs], red blood cells [RBCs], hemoglobin, hematocrit, and platelets).
Methods: In a 12-week, randomized, double-blind study, we randomly assigned BD patients to one of three groups: VPA plus either placebo (VPA+P, n = 57) or DM (30 mg/day, VPA+DM30, n = 56) or 60 mg/day (VPA+DM60, n = 53). The Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS) were used to evaluate symptom severity, and the hematological molecules were checked.
Results: Paired T-test showed that the WBC, neutrophils, platelets and RBCs were significantly lowered after 12 weeks of VPA+P or VPA+DM30 treatment. VPA+DM60 represented the protective effects in the WBCs, neutrophils, and RBCs but not in the platelets. We further calculated the changes of each hematological molecules after 12 weeks treatment. We found that combination use of DM60 significantly improved the decline in neutrophils induced by the long-term VPA treatment.
Conclusion: Hematological molecule levels were lower after long-term treatment with VPA. VPA+DM60, which yielded the protective effect in hematological change, especially in the neutrophil counts. Thus, DM might be adjunct therapy for maintaining hematological molecules in VPA treatment.
Keywords: bipolar disorder (BD), dextromethorphan (DM), neutrophils, platelet, red blood cells (RBC), valproic acid (VPA).


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