Valproate-Risperidone versus Valproate-Lithium combination in acute mania
Abstract
Background: We evaluated the efficacy of valproate plus risperidone versus valproate plus lithium combination in the treatment of acute mania.
Methods: In 2-week, randomized, double-blind, parallel group study, 46 acute manic patients according to DSM-IV criteria were randomly assigned to receive combination of valproate 20 mg/ kg/day plus risperidone 2-4 mg/day (n=23) or lithium600-1200 mg/day (n=23). The assessment of efficacy measures were according to Young Mania Rating Scale (YMRS) and Clinical Global Impressions-Severity (CGI-S) and Improvement (CGI-I) scale. Other effectiveness measures included YMRS response (YMRS reduction >50 %) and YMRS remission (YMRS total scores <12).
Results: In each group, 16 of 23 patients (70 %) completed the study. YMRS response, CGI-Improvement, and reduction in the total scores of YMRS and CGI-S observed in both groups, significantly greater for valproate-risperidone than valproate-lithium combination group (P=0.006, P=0.015, P=0.004, and P=0.007, respectively).YMRS remission were shown in both groups without statistical significance (P=0.073). The total scores of YMRS at 4th, 8th, and 14th days of trial were lower in valproate-risperidone than valproate-lithium combination group (P=0.017, P=0.005, and P=0.004, respectively). The rate of adverse events and mean weight gain in both groups were not statistically different.
Conclusion: In acute manic patients, both combinations of valproate with lithium or with risperidone had efficacy in acutely manic patients, but valproate-risperidone combination was more effective. Both treatments were safe and well tolerated. Considering the small sample size and limited period of observation, further studies need to be conducted to find out the best combination in the treatment of acute mania.
Key words: Acute mania, Valproate, Risperidone, Lithium, Combination Therapy
Methods: In 2-week, randomized, double-blind, parallel group study, 46 acute manic patients according to DSM-IV criteria were randomly assigned to receive combination of valproate 20 mg/ kg/day plus risperidone 2-4 mg/day (n=23) or lithium600-1200 mg/day (n=23). The assessment of efficacy measures were according to Young Mania Rating Scale (YMRS) and Clinical Global Impressions-Severity (CGI-S) and Improvement (CGI-I) scale. Other effectiveness measures included YMRS response (YMRS reduction >50 %) and YMRS remission (YMRS total scores <12).
Results: In each group, 16 of 23 patients (70 %) completed the study. YMRS response, CGI-Improvement, and reduction in the total scores of YMRS and CGI-S observed in both groups, significantly greater for valproate-risperidone than valproate-lithium combination group (P=0.006, P=0.015, P=0.004, and P=0.007, respectively).YMRS remission were shown in both groups without statistical significance (P=0.073). The total scores of YMRS at 4th, 8th, and 14th days of trial were lower in valproate-risperidone than valproate-lithium combination group (P=0.017, P=0.005, and P=0.004, respectively). The rate of adverse events and mean weight gain in both groups were not statistically different.
Conclusion: In acute manic patients, both combinations of valproate with lithium or with risperidone had efficacy in acutely manic patients, but valproate-risperidone combination was more effective. Both treatments were safe and well tolerated. Considering the small sample size and limited period of observation, further studies need to be conducted to find out the best combination in the treatment of acute mania.
Key words: Acute mania, Valproate, Risperidone, Lithium, Combination Therapy