Paliperidone 263mg/1.315ml prolonged-release suspension for injection pre-filled syringes

ObjectiveTo compare the short-term efficacy and tolerability of second-generation antipsychotics (SGAs) versus placebo for schizophrenia-spectrum disorders in children and adolescents using pairwise meta-analysis of randomized trials, and to summarize prospective long-term evidence.MethodsWe pooled acute double-blind randomized controlled trials (RCTs) (≤12 weeks; participants ≤19 years; Diagnostic and Statistical Manual of Mental Disorders [DSM]/International Classification of Diseases [ICD] schizophrenia-spectrum) with random-effects models. Efficacy was change in Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale [BPRS] total score, expressed as standardized mean difference (SMD) versus placebo. Short-term tolerability was defined as adverse event-related outcomes and expressed as risk ratios (RRs) for potentially drug-related treatment-emergent adverse events (TEAEs) versus placebo. Trials without a placebo arm and long-term prospective studies were synthesized narratively.ResultsSeventeen acute RCTs were identified; ten were placebo-controlled and entered pooling (agents: olanzapine [OLZ], risperidone [RSP], asenapine [ASP], aripiprazole [APZ], brexpiprazole [BRX], blonanserin [BNS], quetiapine [QTP], lurasidone [LUR], paliperidone [PAL], ziprasidone [ZPD]); seven head-to-head or open-label trials were not pooled. Placebo-referenced efficacy favored several agents: OLZ -1.12 [-1.44 to -0.81], RSP -0.93 [-1.22 to -0.63], BNS -0.50 [-0.89 to -0.11], ASP -0.41 [-0.65 to -0.17], APZ -0.37 [-0.61 to -0.13], BRX -0.34 [-0.61 to -0.07], QTP -0.33 [-0.61 to -0.06], LUR -0.31 [-0.54 to -0.08], PAL -0.25 [-0.57 to -0.07], and ZPD -0.06 [-0.31 to -0.19]. For tolerability, most drugs showed numerically higher TEAE risk versus placebo with wide confidence intervals (typical RR ≈ 2-3); APZ showed a statistically higher risk (RR 2.34 [1.42-3.86]), whereas the point estimate for LUR was below 1 (0.47 [0.18-1.17]). One randomized maintenance study and 12 open-label extensions were reviewed narratively and were not meta-analyzed.ConclusionsSeveral SGAs produce short-term symptom reductions versus placebo in children and adolescents with schizophrenia-spectrum disorders, with heterogeneity in TEAE risk across agents. Evidence for long-term maintenance and continuation remains limited, underscoring the need for adequately powered randomized continuation trials to guide sustained treatment in this population.

Abstract licence: CC BY

AbstractIs paliperidone palmitate (PP) a useful treatment option for adults with acute symptoms of schizophrenia? We conducted a systematic review and a random-effects pairwise and network meta-analysis that compared PP (25−150 mg equivalent) with paliperidone extended-release (PAL-ER, 3−12 mg/d) regarding their efficacy and safety in adults with acute symptoms of schizophrenia. The outcomes were the total score of the Positive and Negative Syndrome Scale (PANSS-T) at week 6 (the primary outcome for efficacy) and all-cause discontinuation(the primary outcome for acceptability), discontinuation due to inefficacy, discontinuation due to adverse events, discontinuation due to the withdrawal of consent, and the incidence of individual adverse events. Five studies on PP and seven studies on PAL-ER, which involved 4970 individuals in total, were included in this study. For the primary outcomes, we only included data from the treatment arms that used 100 or 150 mg equivalent as an initial dose of PP and data from the treatment arms that used 6, 9, or 12 mg as an initial dose of PAL-ER. The pairwise meta-analyses showed that both PP and PAL-ER outperformed placebo regarding PANSS-T at week 6 and all-cause discontinuation. However, there were no statistically significant differences in these outcomes between the effect sizes of PP and that of PAL-ER. Both PP and PAL-ER increased blood prolactin levels in both females and males compared with placebo. PAL-ER significantly increased blood prolactin in both females and males compared with PP. There were no statistically significant differences in other outcomes between the effect sizes of PP and that of PAL-ER. Similar results in all outcomes were observed in the network meta-analyses. In conclusion, PP might be a useful treatment option for adults with acute symptoms of schizophrenia. A noninferiority study that directly compares PP with PAL-ER for acute schizophrenia, conducted according to the recommended regimen, is required to provide solid evidence.

Abstract licence: CC BY 4.0