Safety of aripiprazole for tics in children and adolescents: A systematic review and meta-analysis

BACKGROUND: Aripiprazole is widely used in the management of tic disorders (TDs), we aimed to assess the safety of aripiprazole for TDs in children and adolescents. METHODS: A systematic literature review was performed in the databases of MEDLINE, Embase, the Cochrane Library and 4 Chinese databases, from inception to February 2019. All types of studies evaluating the safety of aripiprazole for TDs were included. The quality of studies was assessed using the Cochrane Risk of Bias tool, the Newcastle–Ottawa Scale tool, the National Institute of Clinical Excellence, the CARE (Case Report) guidelines according to types of studies. Risk ratio (RR) and incidence rate with a 95% confidence interval (CI) were used to summarize the results. RESULTS: A total 50 studies involving 2604 children met the inclusion criteria. The result of meta-analysis of randomized controlled trials showed that there was a significant difference between aripiprazole and haloperidol with respect to rate of somnolence (RR = 0.596, 95% CI: 0.394, 0.901), extrapyramidal symptoms (RR = 0.236, 95% CI: 0.111, 0.505), tremor (RR = 0.255, 95% CI: 0.114, 0.571), constipation (RR = 0.148, 95% CI: 0.040, 0.553), and dry mouth (RR = 0.141, 95% CI: 0.046, 0.425). There was a significant difference between aripiprazole and placebo in the incidence rate of adverse events (AEs) for somnolence (RR = 6.565, 95% CI: 1.270, 33.945). The meta-analysis of incidence of AEs related to aripiprazole for case series studies revealed that the incidence of sedation was 26.9% (95% CI: 16.3%, 44.4%), irritability 25% (95% CI: 9.4%, 66.6%), restlessness 31.3% (95% CI: 13%, 75.1%), nausea and vomiting 28.9% (95% CI: 21.1%, 39.5%), and weight gain 31.3% (95% CI: 10.7%, 91.3%). CONCLUSION: Aripiprazole was generally well tolerated in children and adolescents. Common AEs were somnolence, headache, sedation, nausea, and vomiting. Further high-quality studies are needed to confirm the safety of aripiprazole for children and adolescents with TDs.