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

Abstract

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.

Does the Ranking Matter? A Retrospective Cohort Study Investigating the Impact of the 2018 CANMAT and ISBD Guidelines for the Management of Patients with Bipolar Disorder Treatment Recommendations for Acute Mania on Rehospitalization Rates

“… 20 Lurasidone use may also have contributed to the positive results of the noncompliant regimens in preventing any rehospitalization. Despite its efficacy in bipolar depression 21 and schizophrenia 22 and potential usefulness as an antimanic agent due to antipsychotic activity, there are no studies of lurasidone in mania and it is not listed as a recommended treatment by the guidelines. Unfortunately, due to the number of individuals and the large variability of medications in the noncompliant group, we were not able to explore the effect of each specific medication or combination on study outcomes.…”

Cost analysis of lurasidone for the treatment of schizophrenia in adolescents and adults within the United Kingdom

“…The six-weekly probability discontinuation of haloperidol due to intolerable adverse events was also taken from an NMA analysis of the dose–response effects of lurasidone on acute schizophrenia [ 19 ]. This NMA reported results of the opposite direction for all dosages of lurasidone, which may positively bias the adolescent results in favour of lurasidone.…”

“…Furthermore, clozapine was not included within either NMA. Therefore, the probabilities of discontinuation associated with haloperidol and clozapine were obtained from alternative sources [ 18 , 19 ]. Further information regarding the derivation of the six-weekly discontinuation probabilities is presented within the supplementary material (Sect.…”

“…Lurasidone: adolescents (80 mg) 1.3% [15] 8.8% [15] 2.1% [17] 5.9% [18] 28.7% [18] Haloperidol (3 mg) 8.0% [19] 7.5% [18] 4.9% [20] 9.7% [18] 46.2% [18] Paliperidone (6 mg) 3.4% [15] 3.8% [15] 1.9% [17] 14.7% [18] 23.8% [18] Aripiprazole (10 mg) 15.3% [15] 25.7% [15] 4.6% [17] 9.0% [18] 19.5% [18] Lurasidone: adults (148 mg) 7.6% [16] 18.2% [16] 2.1% [17] 5.9% [18] 28.7% [18] Brexpiprazole (4 mg) 5.6% [16] 25.6% [16] 2.5% [17] 13.5% [18] 23.7% [18] Cariprazine (6 mg) 8.5% [16] 28.8% [16] 3.7% [17] 5.6% [18] 32.7% [18] Clozapine NA 5.4% [18] 4.9% [21] 33.3% [22] 6.8% [18] No treatment NA NA 7.1% [17] NA NA…”

Omówienie wybranych metod współczesnej terapii schizofrenii

“…[55], porównując dane z czterech badań z randomizacją i grupą kontrolną (w których wzięło udział ponad 3000 chorych) [56][57][58][59] Manit Srisurapanont i wsp. [64] opublikowali w 2021 roku metaanalizę, porównującą 10 badań (uczestniczyło w nich łącznie 3366 osób dorosłych z zaostrzeniem schizofrenii) z zastosowaniem lurazydonu w różnych dawkach pod kątem oceny jego skuteczności i bezpieczeństwa. Uwzględniono następujące dawki terapeutyczne lurazydonu: 20 mg, 40 mg, 80 mg, 120 mg, 160 mg, stosowane u osób dorosłych ze zdiagnozowaną schizofrenią w fazie zaostrzenia.…”