Open-label prospective trial of risperidone in combination with lithium or divalproex sodium in pediatric mania.

Objective: This prospective 6-month open trial examined the safety and efficacy of two combination therapies for manic or mixed episodes of pediatric bipolar disorder: (1) divalproex sodium plus risperidone (DVPX+Risp), or (2) lithium plus risperidone (Li+Risp).

Methods: Thirty-seven (37) subjects aged 5 and 18 (age=12.1+/-3.5 years) with DSM IV current mixed or manic episode and Young Mania Rating Scale (YMRS) score >20 were sequentially assigned to either DVPX+Risp or Li+Risp in a 6-month, prospective open-label trial. Outcome measures included the YMRS, Clinical Global Impression Scale for Bipolar Disorder (CGI-BP), Child Depression Rating Scale-Revised (CDRS-R) as well as measures of safety and tolerability.

Results: Effect sizes (Cohen's d) based on change of YMRS scores from baseline were 4.36 for DVPX+Risp and 2.82 for Li+Risp. Response rates (>or=50% change from baseline YMRS score at the end of study) were 80% for DVPX+Risp and 82.4% for Li+Risp. Both combination treatments were well tolerated. Significant improvements (p<0.001) from baseline were seen for mean scores on all efficacy measures, i.e., YMRS, CGI-BP, and CDRS-R. There were no significant group differences in safety or tolerability, and no serious adverse events during the 6-month trial.

Conclusion: Both DVPX+Risp and Li+Risp show strong effects coupled with safety and tolerability in treating children and adolescents with manic or mixed episodes associated with type I bipolar disorder.