A network meta-analysis of the dose–response effects of lurasidone on acute schizophrenia

• Published in: Scientific reports 2021-03, Vol.11 (1), p.5571-13, Article 5571
• Main Authors: Srisurapanont, Manit, Suttajit, Sirijit, Likhitsathian, Surinporn, Maneeton, Benchalak, Maneeton, Narong
• Format: Article
• Language: English
• Subjects: 631/154/436/108; 692/699/476/1799; Acute Disease; Antipsychotics; Dose-Response Relationship, Drug; Double-Blind Method; Humanities and Social Sciences; Humans; Lurasidone Hydrochloride - adverse effects; Lurasidone Hydrochloride - therapeutic use; Mental disorders; Meta-analysis; multidisciplinary; Network Meta-Analysis; Placebos; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenia - drug therapy; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-84836-z

We compared the efficacy, safety, and acceptability of lurasidone at different doses to establish the dose–response relationships of lurasidone therapeutic and adverse effects in acute schizophrenia. Included trials were 4- to 16-week, fixed-dose, randomized controlled trials of lurasidone in adults with acute schizophrenia. Different doses of lurasidone, other antipsychotics, and placebo were considered as independent treatments. Apart from all-cause dropout rates, four therapeutic and four adverse outcomes were included in the frequentist network meta-analysis (NMA). Lurasidone 160, 120, 80, 40, and 20 mg/day were studied in ten trials of 3,366 adults with schizophrenia exacerbation. Lurasidone 160 mg/day reduced Positive and Negative Syndrome Scale (PANSS) total scores significantly more than lurasidone 120, 80, 40, and 20 mg/day (mean differences = − 7.63, − 7.04, − 8.83, and − 12.25, respectively). All-cause dropout rates were significantly lower in participants receiving lurasidone 160 mg/day and 80 mg/day compared with those taking placebo. The half-maximal effective doses of lurasidone for PANSS total, PANSS positive, and MADRS score reductions were higher than 80 mg/day. The confidence of all NMA estimates was low or very low. Lurasidone 160 mg/day is currently the most efficacious and acceptable dose for acute schizophrenia. Its maximal effective doses may be higher than 160 mg/day.