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

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.

Keywords: Bipolar disorder; Blood platelets; Dextromethorphan; Erythrocytes; Neutrophils; Valproic acid.

Fig. 1

Enrollment, randomization, and follow-up in National Cheng Kung University (NCKU) Hospital. DM, dextromethorphan. VPA, valproic acid.

Fig. 2

The changes of hematological molecules in patients with bipolar disorder (BD) after 12 weeks treatment with VPA+Placebo (n = 57), VPA+ DM30 (n = 56) and VPA+DM60 (n = 53). The changes of (A) white blood cell (WBC) counts, (B) neutrophils counts, (C) red blood cell (RBC) counts and (D) platelet counts were calculated and analyzed between groups. All data are mean ± standard error of the mean. All measurement are cell counts in one cubic millimeters (cmm); *p < 0.05, vs. VPA+Placebo group (One-Way ANOVA with Tucky post-hoc test). DM, dextromethorphan. VPA, valproic acid.