LAUSR

Abstract Background Childhood and adolescent schizophrenia is a severe and debilitating disorder associated with long-term impairments in functioning, poor physical health, and reduced life expectancy. Compared with adult-onset schizophrenia, childhood and adolescent schizophrenia may be a more severe disorder, negatively influencing social, cognitive and psychological development, educational achievements and life-long occupational functioning. Therefore, treatment of childhood and adolescent schizophrenia is highly important and presents a major therapeutic challenge. The aim of this systematic review and meta-analysis was to assess whether antipsychotics (APs) have different clinical benefits and harms profiles in acute treatment of childhood and adolescent schizophrenia. Methods We conducted systematic review and meta-analysis of randomized placebo-controlled trials (RCTs) assessing efficacy and adverse effects of APs in acute childhood and adolescent schizophrenia to compare clinical benefits and harms. An electronic search was conducted without language restrictions using Embase, Scopus, MEDLINE/PubMed, the Cochrane library, and the US National Institutes of Health clinical trials registry (http://www.clinicaltrials.gov). The electronic search was supplemented by a hand search of reference lists of relevant studies and reviews. The primary efficacy outcome examined was treatment response. The primary safety/tolerability was assessed based on discontinuation due to adverse event. In order to visualize the risk and benefit tradeoff of each AP, risk ratios (RRs) were plotted on two-dimensional graph for the primary efficacy and safety/tolerability outcomes. Results Ten studies were selected, comprising of 2,271 patients across eight active interventions (aripiprazole, asenapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone) and placebo. The mean intervention duration was 6.4 weeks (range 6–8 weeks). Lurasidone, asenapine and risperidone had significantly higher response rate (RR = 1.54, 95% CI = 1.21 to 1.95, p<0.001; RR = 1.38, 95% CI = 1.02 to 1.85, p=0.035; and RR = 1.71, 95% CI = 1.39 to 2.11, p<0.001, respectively) compared with placebo. These three antipsychotics also had significant single digit numbers needed to treat (NNT = 5, 4, and 8, respectively). All APs did not significantly separate from placebo in discontinuation rate due to adverse event compared with placebo (RR = 0.47 to 5.42). Aripiprazole had the significant number needed to harm (NNH = 25). On a two-dimensional graph plot of efficacy and safety/tolerability, lurasidone showed the most desirable profile for the risk / benefit tradeoff balance among all antipsychotics. Discussion Results from this meta-analysis illustrate that there are significant differences in benefits and harms among APs in the treatment of childhood and adolescent schizophrenia. Medications choice needs to be carefully evaluated to achieve optimal clinical benefit while minimizing burden of side effects for the patients.