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Lurasidone compared to other atypical antipsychotic monotherapies for adolescent schizophrenia: a systematic literature review and network meta-analysis.

ABSTRACT: This network meta-analysis assessed the efficacy and tolerability of lurasidone versus other oral atypical antipsychotic monotherapies in adolescent schizophrenia. A systematic literature review identified 13 randomized controlled trials of antipsychotics in adolescents with schizophrenia-spectrum disorders. A Bayesian network meta-analysis compared lurasidone to aripiprazole, asenapine, clozapine, olanzapine, paliperidone extended-release (ER), quetiapine, risperidone, and ziprasidone. Outcomes included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity (CGI-S), weight gain, all-cause discontinuation, extrapyramidal symptoms (EPS), and akathisia. Results were reported as median differences for continuous outcomes and odds ratios (ORs) for binary outcomes, along with 95% credible intervals (95% CrI). Lurasidone was significantly more efficacious than placebo on the PANSS (-?7.95, 95% CrI -?11.76 to -?4.16) and CGI-S (-?0.44, 95% CrI -?0.67 to -?0.22) scores. Lurasidone was associated with similar weight gain to placebo and statistically significantly less weight gain versus olanzapine (-?3.62 kg, 95% CrI -?4.84 kg to -?2.41 kg), quetiapine (-?2.13 kg, 95% CrI -?3.20 kg to -?1.08 kg), risperidone (-?1.16 kg, 95% CrI -?2.14 kg to -?0.17 kg), asenapine (-?0.98 kg, 95% CrI -?1.71 kg to -?0.24 kg), and paliperidone ER (-?0.85 kg, 95% CrI -?1.57 kg to -?0.14 kg). The odds of all-cause discontinuation were significantly lower for lurasidone than aripiprazole (OR?=?0.28, 95% CrI 0.10-0.76) and paliperidone ER (OR?=?0.25, 95% CrI 0.08-0.81) and comparable to other antipsychotics. Rates of EPS and akathisia were similar for lurasidone and other atypical antipsychotics. In this network meta-analysis of atypical antipsychotics in adolescent schizophrenia, lurasidone was associated with similar efficacy, less weight gain, and lower risk of all-cause discontinuation compared to other oral atypical antipsychotics.

SUBMITTER: Arango C

PROVIDER: S-EPMC7497364 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Lurasidone compared to other atypical antipsychotic monotherapies for adolescent schizophrenia: a systematic literature review and network meta-analysis.

Arango Celso C Ng-Mak Daisy D Finn Elaine E Byrne Aidan A Loebel Antony A

European child & adolescent psychiatry 20191122 9

This network meta-analysis assessed the efficacy and tolerability of lurasidone versus other oral atypical antipsychotic monotherapies in adolescent schizophrenia. A systematic literature review identified 13 randomized controlled trials of antipsychotics in adolescents with schizophrenia-spectrum disorders. A Bayesian network meta-analysis compared lurasidone to aripiprazole, asenapine, clozapine, olanzapine, paliperidone extended-release (ER), quetiapine, risperidone, and ziprasidone. Outcomes ...[more]

PMID: 31758359

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Project description:Abstract Background: Lurasidone is an atypical antipsychotic agent that has demonstrated efficacy in the treatment of adults with schizophrenia in the dose range of 40–160?mg/d. The objective of this randomized, double-blind, placebo-controlled study was to evaluate the acute efficacy and safety of lurasidone in adolescent patients with schizophrenia. Methods: Adolescents (13–17 years old) diagnosed with schizophrenia were randomly assigned to 6 weeks of double-blind treatment with fixed-dose lurasidone 40?mg/d, 80?mg/d, or placebo. Changes from baseline to Week 6 in PANSS total and subscale (positive, negative, general psychopathology, excitability) scores were evaluated using mixed-model, repeated-measures analysis. Treatment response was defined as ?20% reduction from baseline in PANSS total score at Week 6 and was analyzed using a logistic regression model with last observation carried forward (LOCF) approach. Results: A total of 326 patients (mean age, 15.4 years) were randomized and received lurasidone 40?mg/d (N = 108), 80?mg/d (N = 106), or placebo (N = 112). The PANSS total score at Week 6 demonstrated a placebo-adjusted, least-squares (LS) mean improvement of ?8.0 (P < .001; effect size [ES] = 0.51) for the 40?mg/d group and ?7.7 (P < .001; ES = 0.48) for the 80?mg/d group. Placebo-adjusted LS mean change for lurasidone 40?mg/d and 80?mg/d, respectively, was ?3.2 (P < .001; ES = 0.62) and ?3.2 (P < .001; ES = 0.60) on the PANSS positive subscale, ?1.7 (P = .011; ES = 0.41) and ?1.6 (P = .022; ES = 0.35) on the PANSS negative subscale, ?2.8 (P = .012; ES = 0.38) and ?2.8 (P = 0.011; ES = 0.37) on the PANSS general psychopathology subscale, and ?1.1 (P = .016; ES = 0.36) and ?1.8 (P < .001; ES = 0.53) on the PANSS excitability subscale. The proportion of treatment responders at Week 6 (LOCF) was 42.0% in the placebo group, 63.9% in the lurasidone 40?mg/d group (P < .001; NNT = 5), and 65.1% in the lurasidone 80?mg/d group (P < .001; NNT = 5). The most common adverse events (incidence ?5% in either lurasidone group and at least twice the rate of placebo) for lurasidone 40?mg/d, 80?mg/d, and placebo, respectively, were nausea (12.7%, 14.4%, and 2.7%), somnolence (9.1%, 11.5%, and 5.4%), akathisia (9.1%, 8.7%, and 1.8%), vomiting (8.2%, 6.7%, and 1.8%), and sedation (5.5%, 1.9%, and 1.8%). The rate of study discontinuation due to adverse events was higher in placebo-treated versus lurasidone-treated patients (8.0% vs. 3.7%, respectively). Conclusion: In this double-blind, placebo-controlled study of adolescent patients with schizophrenia, lurasidone (40?mg/d and 80?mg/d) demonstrated statistically significant efficacy and clinically meaningful improvement across a range of symptoms associated with this disorder. Lurasidone treatment was generally safe and well tolerated in this study. Sponsored by Sunovion Pharmaceuticals Inc. ClinicalTrials.gov identifier: NCT01911429

Project description:STUDY OBJECTIVE:Patients with schizophrenia are known to have higher rates of metabolic disease than the general population. Contributing factors likely include lifestyle and atypical antipsychotic (AAP) use, but the underlying mechanisms are unknown. The objective of this study was to identify metabolomic variability in adult patients with schizophrenia who were taking AAPs and grouped by fasting insulin concentration, our surrogate marker for metabolic risk. DESIGN:Metabolomics analysis PARTICIPANTS: Ninety-four adult patients with schizophrenia who were taking an AAP for at least 6 months, with no changes in their antipsychotic regimen for the previous 8 weeks, and who did not require treatment with insulin, participated in the study. Twenty age- and sex-matched nonobese (10 subjects) and obese (10 subjects) controls without cardiovascular disease or mental health diagnoses were used to match the body mass index (BMI) range of the patients with schizophrenia to account for metabolite concentration differences attributable to BMI. MEASUREMENTS AND MAIN RESULTS:Existing serum samples were used to identify aqueous metabolites (to differentiate fasting insulin concentration quartiles) and fatty acids with quantitative nuclear magnetic resonance and gas chromatography methods, respectively. To exclude metabolites from our pathway mapping analysis that were due to variability in weight, we also subjected serum samples from the nonobese and obese controls to the same analyses. Patients with schizophrenia had a median age of 47.0 years (interquartile range 41.0-52.0 years). Using a false discovery rate threshold of less than 25%, 10 metabolites, not attributable to weight, differentiated insulin concentration quartiles in patients with schizophrenia and identified variability in one-carbon metabolism between groups. Patients with higher fasting insulin concentrations (quartiles 3 and 4) also trended toward higher levels of saturated fatty acids compared with patients with lower fasting insulin concentrations (quartiles 1 and 2). CONCLUSION:Our results illustrate the utility of metabolomics to identify pathways underlying variable fasting insulin concentration in patients with schizophrenia. Importantly, no significant difference in AAP exposure was observed among groups, suggesting that current antipsychotic use may not be a primary factor that differentiates middle-aged adult patients with schizophrenia by fasting insulin concentration.

Project description:INTRODUCTION:Antipsychotic treatment in early-onset schizophrenia (EOS) lacks a rich evidence base, and efforts to rank different drugs concerning their efficacy have not proven any particular drug superior. In contrast to the literature regarding adult-onset schizophrenia (AOS), comparative effectiveness studies in children and adolescents are limited in number and size, and only a few meta-analyses based on conventional methodologies have been conducted. METHODS AND ANALYSES:We will conduct a network meta-analysis of all randomised controlled trials (RCTs) that evaluate antipsychotic therapies for EOS to determine which compounds are efficacious, and to determine the relative efficacy and safety of these treatments when compared in a network meta-analysis. Unlike a contrast-based (standard) meta-analysis approach, an arm-based network meta-analysis enables statistical inference from combining both direct and indirect comparisons within an empirical Bayes framework. We will acquire eligible studies through a systematic search of MEDLINE, the Cochrane Central Registry of Controlled Trials, Clinicaltrials.gov and Centre for Reviews and Dissemination databases. Eligible studies should randomly allocate children and adolescents presenting with schizophrenia or a related non-affective psychotic condition to an intervention group or to a control group. Two reviewers will-independently and in duplicate-screen titles and abstracts, complete full text reviews to determine eligibility, and subsequently perform data abstraction and assess risk of bias of eligible trials. We will conduct meta-analyses to establish the effect of all reported therapies on patient-relevant efficacy and safety outcomes when possible. ETHICS AND DISSEMINATION:No formal ethical procedures regarding informed consent are required as no primary data collection is undertaken. The review will help facilitate evidence-based management, identify key areas for future research, and provide a framework for conducting large systematic reviews combining direct and indirect comparisons. The study will be disseminated by peer-reviewed publication and conference presentation. TRIAL REGISTRATION NUMBER:PROSPERO CRD42013006676.

Dataset Information

Lurasidone compared to other atypical antipsychotic monotherapies for adolescent schizophrenia: a systematic literature review and network meta-analysis.

Publications

Lurasidone compared to other atypical antipsychotic monotherapies for adolescent schizophrenia: a systematic literature review and network meta-analysis.

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