A meta-analysis of efficacy and safety of aripiprazole in adult and paediatric bipolar disorder in randomized controlled trials and observational studies

Background Aripiprazole (ARP) has been shown to be effective in the treatment of bipolar disorder (BD). However, no prior investigation considered both randomized clinical trials (RCTs) and non-RCTs. We here evaluated the efficacy and safety of ARP compared with placebo (PCB) and other drugs at 3- and 12-weeks in adult and pediatric population including, for the first time, both observational and controlled studies. Methods All studies were systematically located by searching electronic sources (EMBASE, MEDLINE, CINHAIL, PsychINFO, Cochrane Central Register of Controlled Trials, Scopus and ClinicalTrials.gov) till June 30th, 2015. The primary outcome was ARP efficacy (mean change from baseline in Young Mania Rating Scale); secondary outcomes regarded acceptability and safety. Results Sixteen RCTs and 6 non-RCTs met our inclusion criteria; 2505 and 2932 patients were included in the analyses of acute and stabilization phase, respectively. In both the acute and stabilization phases ARP efficacy was superior to PCB and comparable to other drugs. The safety profile was similar to other drugs considering in particular sedation, akathisia, weight gain, extrapyramidal and gastroenteric symptoms, with a significant lower risk of hyperprolactinemia particularly at 12-weeks. Limitations Data on failed trials are generally limited. Conclusions ARP resulted to be an effective treatment in children and adults with BD at 3- and 12-weeks both in a controlled experimental setting or in the real world clinical practice, being poorly associated with hyperprolactinemia. Larger studies are needed to confirm our results related to the maintenance phases and to the pediatric bipolar population.