Introduction: By increasing the number of effective treatments, mania is still remains a challenging problem for health systems. The aim of this study was to compare the efficacy of risperidone and aripiprazole in combination with sodium valproate in bipolar patients with acute manic or mixed episodes who were hospitalized in Razi Psychiatric Hospital in Tehran.

Methods: This study was conducted as a double-blind randomized clinical trial in two groups of bipolar disorder patients with manic or mixed episodes (age rage, 18-65 years). The patients were randomly categorized into two groups who received valproate with aripiprazole or risperidone. The clinical response was assessed by the Young mania rating scale and weight gain within 3 and 6 weeks. Data were analyzed using the Chi-square test, paired t-test and analysis of covariance and repeated measures.

Results: The study participants had no significant difference in demographic characteristics. Evaluation of the treatment response after 3 and 6 weeks (50% reduction in the Young's scale) in both groups showed no significant difference between the two therapeutic combinations. The combination of sodium valproate and risperidone showed higher weight gain in comparison with the combination of valproate and aripiprazole at the end of the week 6 (P < 0.001).

Conclusions: The mentioned therapeutic combinations in the bipolar I disorder with a manic or mixed episode have a similar therapeutic effect. Also, there was no significant difference in their efficacy and both treatments can be used. However, due to the less weight gain, the combination of valproate and aripiprazole is recommended as a safer and more effective therapy in patients who were prone to weight gain.