Is asenapine or aripiprazole more effective than a placebo for reducing episodes of mania in children with bipolar I disorder

Objective: The objective of this selective EBM review is to determine whether or not asenapine or aripiprazole are more effective than a placebo for reducing episodes of mania in children with bipolar I disorder. Study Design: Review of two randomized control trials (RCTs) published in 2013 and 2015, and a flexible-dose, open-label, extension study published in 2016. Data Sources: Each article used was published in English and found using PubMed database. All articles were published in peer-reviewed journals. Outcomes Measured: The clinical superiority of asenapine and aripiprazole were measured by a change in baseline in the Young Mania Rating Scale (YMRS) total score. A decrease in YMRS score indicates improved mania symptoms. Results: Findling, et al. (2015) found that all studied doses of asenapine were more effective than a placebo at reducing the baseline score of the Young Mania Rating Scale (YMRS) [for 2.5 mg: -12.8 vs -9.6, p=0.008; for 5mg -14.9 vs -9.6, p <0.001; for 10mg: - 15.8 vs -9.6, p <0.001]. Findling, et al. (2013) found that all doses of aripiprazole were more effective than a placebo using the same YMRS change from baseline [for 10mg: - 14.1 vs -8.2, p <0.001; for 30 mg: -14.9 vs -8.2, p <0.001]. This article also examined the average time to withdrawal [for 10 mg 15.6 weeks vs 5.3, p <0.001; for 30 mg 9.5 vs 5.3, p <0.05]. The Findling, et al. (2016) open-label, extension study found that there was a greater mean change in baseline YMRS total scores in the placebo/asenapine population (-13.0 at 26 weeks and -15.2 at 50 weeks), a 79.2% total population of patients that were YMRS 50% responders, and 68.5% of all patients achieved YMRS remission. Conclusions: Though each study reported an improvement of symptoms, the efficacy of asenapine and aripiprazole over a placebo for the treatment of mania episodes in children with bipolar I disorder cannot be determined due to the limitations in experimental design and validity.