title: Adverse events and treatment failure leading to discontinuation of recently approved antipsychotic drugs in schizophrenia: A network meta-analysis.
abstract: Objective:We aimed to gather evidence of the discontinuation rates owing to adverse events or treatment failure for four recently approved antipsychotics (asenapine, blonanserin, iloperidone, and lurasidone).Methods: A systematic review followed by pairwise meta-analysis and mixed treatment comparison meta analysis(MTC) was performed, including randomized controlled trials (RCTs) that compared the use of the above-mentioned drugs versus placebo in patients with schizophrenia. An electronic search was conducted in PubMed, Scopus, Science Direct, Scielo, the Cochrane Library, and International Pharmaceutical Abstracts(January 2015). The included trials were at least single blinded. The main outcome measures extracted were discontinuation owing to adverse events and discontinuation owing to treatment failure.Results: Fifteen RCTs were identified (n = 5400 participants) and 13 of them were amenable for use in our meta-analyses. No significant differences were observed between any of the four drugs and placebo as regards discontinuation owing to adverse events, whether in pairwise meta-analysis or in MTC. All drugs presented a better profile than placebo on discontinuation owing to treatment failure, both in pairwise meta-analysis and MTC. Asenapine was found to be the best therapy in terms of tolerability owing to failure,while lurasidone was the worst treatment in terms of adverse events. The evidence around blonanserin is weak.Conclusion: MTCs allowed the creation of two different rank orders of these four antipsychotic drugs in two outcome measures. This evidence-generating method allows direct and indirect comparisons, supporting approval and pricing decisions when lacking sufficient, direct, head-to-head trials.
authors.affiliation: Department of Pharmacy, Pharmaceutical Sciences Postgraduate Research Program, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Fernanda S
authors.initials: FS
authors.lastname: Tonin
authors.affiliation: Department of Pharmacy, Pharmaceutical Sciences Postgraduate Research Program, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Thais
authors.initials: T
authors.lastname: Piazza
authors.affiliation: Department of Pharmacy, Pharmaceutical Sciences Postgraduate Research Program, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Astrid
authors.initials: A
authors.lastname: Wiens
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Department of Social Pharmacy, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal. Electronic address: f-llimos@ff.ul.pt.
authors.forename: Fernando
authors.initials: F
authors.lastname: Fernandez-Llimos
authors.affiliation: Department of Pharmacy, Pharmaceutical Sciences Postgraduate Research Program, Federal University of Paraná, Curitiba, Brazil. Electronic address: pontarolo@ufpr.br.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pontarolo
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D014150:Antipsychotic Agents / Q000009:adverse effects; D007255:Information Services / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents
keywords: Antipsychotic drugs; Network meta-analysis; Schizophrenia