Abstract Introduction: Treatment resistance is common in acute mania, so the role of augmented therapies, including nutritional factors and vitamins have always been considered. This study aimed to assess the effect of addition of folic acid to sodium valproate in treatment of acute mania. Methods: This double blind randomized clinical trial study was done in Mashhad Avicenna psychiatric hospital, in 2011 and was registered with IRCT201112188106N1 code in Iranian registry clinical trials site. Twenty nine manic patients, divided into two groups randomly. They received sodium-valproate+folic acid or sodium-valproate+placebo. The severity of mania, by Jung Mania Rating Scale (YMRS), and cognitional improvement, by Mini-Mental State Examination (MMSE), were determined at baseline, after 3 and 6 weeks. Data analyzed by SPSS-16, к 2 and t-student tests. Result: The mean scores of YMRS at baseline, after 3 and 6 weeks, in the folice acid group were 22±2.44, 8.26±4.86 and 3.13±1.64 respectively, and in placebo group were 21.14±1.95, 14.14±4.31 and 13±5.21 respectively. The mean scores of YMRS significantly decreased in the folic acid group compared to the placebo group after 3,6 weeks (p=0.005, p<0.001 respectively). The mean scores of MMSE showed no significant difference in same intervals (p=0.068, p=0.068). Conclusion: Our study showed that adjuvant treatment by folic acid in addition to standard treatment with sodium-valproate during manic phase in patients with BMD-I after 6 weeks of treatment was effective
