Neuroprotective, cognitive, and immunomodulatory effects of Valproic acid combined with dextromethorphan in bipolar disorder.
📄 Abstract
Valproic acid (VPA) is recognized for its neurotrophic properties and is widely used in psychiatric and peripheral disorders, while dextromethorphan (DM) has demonstrated anti-inflammatory and neuroprotective effects. This study examined whether adjunctive DM provides additional benefits on cognitive or immunomodulatory beyond standard VPA treatment in bipolar disorder (BD). BD aged 20-65 received open-label VPA (500-2500 mg/day; target blood level 50-100 μg/dl) for one week and were then randomized to VPA plus placebo (BDVPA) or VPA plus extended-release DM (BDVPA + DM; 30 or 60 mg/day) for twelve weeks. Neuropsychological measures (Continuous Performance Test, CPT; Wechsler Memory Scale-Revised, WMS-R), symptom severity, cytokines, and BDNF were assessed at baseline and post-treatment. A total of 109 participants (mean age 31.04 years, SD = 10.04) were enrolled; 96 completed cognitive testing and blood sampling (66 BD