Clin Psychopharmacol Neurosci.  2020 Feb;18(1):145-152. 10.9758/cpn.2020.18.1.145.

Dextromethorphan Protect the Valproic Acid Induced Downregulation of Neutrophils in Patients with Bipolar Disorder

Affiliations
  • 1Department of Psychiatry, National Cheng Kung University Hospital, Tainan
  • 2Department of Psychology, Asia University, Taichung
  • 3Department of Medical Research, China Medical University Hospital, Taichung
  • 4Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung
  • 5Dpartment of Nursing, Mackay Medical College, Taipei, Taiwan, ROC
  • 6Neurobiology Laboratory, NIH/NIEHS, Research Triangle Park, NC, USA
  • 7Graduate Institute of Medicine & M.Sc. Program in Tropical Medicine, College of Medicine, Kaohsiung Medical University (KMU), Kaohsiung
  • 8Department of Medical Research, KMU Hospital, Kaohsiung, Taiwan, ROC

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 and Hamilton Depression Rating Scale 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.

Keyword

Bipolar disorder; Dextromethorphan; Neutrophils; Blood platelets; Erythrocytes; Valproic acid
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