Behzadi AH, Omrani Z, Chalian M, Asadi S, Ghadiri M. Folic acid efficacy as an alternative drug added to sodium valproate in the treatment of acute phase of mania in bipolar disorder: a double-blind randomized controlled trial. Objective: The purpose of this study was to evaluate the efficacy of adding folic acid to sodium valproate in the acute phase of mania. Method: Following a double-blind randomized controlled trial, 88 clinically manic patients with diagnosis of type I bipolar disorder (BID) were divided randomly into two groups (case and control). The case group was treated with folic acid and sodium valproate and the control group with sodium valproate and placebo. The severity of mania was assessed using the Young Mania Rating Scale (YMRS) at the beginning and end of the first, second and third weeks of the study. Results: The case group’s mean manic YMRS measurements (SD) before the initiation of therapy and in the first, second and third weeks of treatment were 34.0 ± 7.7, 26.7 ± 2.1, 18.1 ± 2.1 and 7.1 ± 0.9 respectively. The control group’s measurements were 34.7 ± 3.8, 27.3 ± 2.3, 20.7 ± 2.5 and 10.1 ± 1.1. There was a statistically significant difference in YMRS scaling results between the case and control groups after 3 weeks of treatment (7.1 ± 0.9 vs. 10.1 ± 1.1, P = 0.005). Conclusion: Based on our findings, folic acid seems to be an effective adjuvant to sodium valproate in the treatment of the acute phase of mania in patients with bipolar disorder.