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Efficacy, tolerability, and safety of lurasidone for acute schizophrenia: A systematic review and network meta-analysis of phase 3 trials in Japan.

ABSTRACT: Introduction: Considering that the efficacy results of the Japan lurasidone phase 3 trials for acute schizophrenia were inconsistent, we conducted a systematic review and a random-effect model network meta-analysis of those trials to examine whether lurasidone was beneficial for the treatment of Japanese patients with acute schizophrenia.

Methods: The study included the double-blind, randomized trial in Japan that included patients with acute schizophrenia. Efficacy outcomes were improvement of the Positive and Negative Syndrome Scale total score (PANSS-T, primary), positive (PANSS-P), negative (PANSS-N), and general (PANSS-G) subscale scores; and Clinical Global Impression-Severity Scale (CGI-S) score and response rate. Other outcomes were discontinuation rates and incidence of individual adverse events.

Results: We included four studies (n = 1,608). Although both lurasidone 40 mg/d (LUR40) and 80 mg/d (LUR80) outperformed placebo in PANSS-T [standardized mean difference (95% credible interval): LUR40 = -0.298 (-0.420, -0.176), LUR80 = -0.170 (-0.320, -0.019)], PANSS-P, and CGI-S scores, LUR40 but not LUR80 outperformed placebo in PANSS-N and PANSS-G scores and response rate. LUR40 outperformed LUR80 regarding PANSS-G score. Both LUR40 and LUR80 were associated with a higher incidence of akathisia, somnolence, and increased body weight compared with placebo. Compared with placebo, LUR40 was associated with a higher incidence of weight gain (?7%), and LUR80 was associated with a higher incidence of dystonia and weight loss (?7%) and higher Drug-Induced Extrapyramidal Symptoms Scale score.

Conclusions: Both LUR40 and LUR80 improved overall symptoms in Japanese patients with acute schizophrenia. However, LUR80 seemed to have a risk of extrapyramidal symptoms.

SUBMITTER: Kishi T

PROVIDER: S-EPMC7722667 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Efficacy, tolerability, and safety of lurasidone for acute schizophrenia: A systematic review and network meta-analysis of phase 3 trials in Japan.

Kishi Taro T Nosaka Tadashi T Sakuma Kenji K Okuya Makoto M Iwata Nakao N

Neuropsychopharmacology reports 20200807 3

<h4>Introduction</h4>Considering that the efficacy results of the Japan lurasidone phase 3 trials for acute schizophrenia were inconsistent, we conducted a systematic review and a random-effect model network meta-analysis of those trials to examine whether lurasidone was beneficial for the treatment of Japanese patients with acute schizophrenia.<h4>Methods</h4>The study included the double-blind, randomized trial in Japan that included patients with acute schizophrenia. Efficacy outcomes were im ...[more]

PMID: 32767739

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Project description:IntroductionUbrogepant is an oral, small-molecule calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine. The efficacy and safety of ubrogepant were demonstrated in two pivotal phase 3, single-attack, randomized, placebo-controlled trials (ACHIEVE I and ACHIEVE II).MethodsWe conducted a post hoc analysis of pooled data from the ACHIEVE trials to evaluate the efficacy, safety, and tolerability of ubrogepant 50 mg (the only dose evaluated in both trials) versus placebo across a large population of participants with migraine. The coprimary efficacy outcomes were pain freedom and absence of the most bothersome migraine-associated symptom (including photophobia, phonophobia, and nausea) at 2 h post dose. Secondary outcomes included pain relief at 2 h post dose, sustained pain relief and pain freedom from 2 to 24 h, and absence of specific migraine-associated symptoms at 2 h post dose.ResultsA total of 2240 eligible participants were randomized to placebo (n = 1122) or ubrogepant 50 mg (n = 1118) in the ACHIEVE trials. Pain freedom at 2 h was reported in 13.0% of participants in the pooled placebo group and 20.5% in the pooled ubrogepant 50 mg group (odds ratio [OR] 1.72; 95% confidence interval [CI] 1.34, 2.22; P < 0.001). Absence of the most bothersome migraine-associated symptom at 2 h was reported by 27.6% in the pooled placebo group and by 38.7% in the pooled ubrogepant 50 mg group (OR 1.68; 95% CI 1.37, 2.05; P < 0.001). Adverse events (AEs) within 48 h after the initial or optional second dose were reported by 11.5 and 11.2% of participants in the pooled placebo and pooled ubrogepant 50 mg groups, respectively. The most common AE was nausea (1.8 and 1.9%, respectively). No serious AEs related to treatment or discontinuations due to AEs were reported.ConclusionThese results further support the efficacy, safety, and tolerability of ubrogepant for the acute treatment of migraine.Trial registrationClinicalTrials.gov Identifiers: ACHIEVE I: NCT02828020; ACHIEVE II: NCT02867709.

Project description:To evaluate the efficacy and safety of lurasidone in acutely symptomatic adolescent patients with schizophrenia.Patients aged 13-17 years were randomly assigned to 6 weeks of double-blind, fixed-dose lurasidone (40 or 80?mg/day) or placebo. Primary and key secondary efficacy measures were change from baseline to week 6 in the Positive and Negative Symptom Scale (PANSS) total score and Clinical Global Impressions-Severity (CGI-S) score, respectively, using mixed model for repeated measurement (MMRM) analysis. The proportion of patients achieving treatment response at endpoint, based on ?20% reduction in PANSS total score, was analyzed using a logistic regression model.Least-squares (LS) mean change in PANSS total score from baseline to week 6 was -18.6 with lurasidone 40?mg/day (N?=?108; p?<?0.001 vs. placebo; effect size?=?0.51), -18.3 with lurasidone 80?mg/day (N?=?106; p?<?0.001 vs. placebo; effect size?=?0.48), and -10.5 with placebo (N?=?112). Similarly, LS mean change in CGI-S score from baseline to week 6 was significantly greater with lurasidone 40?mg/day (-1.0; p?<?0.001; effect size?=?0.49) and 80?mg/day (-0.9; p?=?0.0015; effect size?=?0.45) compared with placebo (-0.5). A significantly higher proportion of patients met responder criteria on lurasidone 40 and 80?mg/day versus placebo (63.9% and 65.1% vs. 42.0%; p?<?0.001 for both comparisons). The rate of study discontinuation was 10.3% in lurasidone-treated and 17.7% in placebo-treated patients. The most common adverse events (incidence ?5% in either lurasidone dose group and at least twice the rate of placebo) for lurasidone 40?mg/day, 80?mg/day, 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%). Treatment with lurasidone was not associated with clinically meaningful effects on body weight, lipids, measures of glycemic control, or prolactin.In this 6-week study, lurasidone at doses of 40 and 80?mg/day demonstrated statistically significant and clinically meaningful symptom improvement in adolescent patients with schizophrenia. Lurasidone was generally well tolerated with few effects on weight and metabolic parameters, consistent with findings in adult patients with schizophrenia.

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Efficacy, tolerability, and safety of lurasidone for acute schizophrenia: A systematic review and network meta-analysis of phase 3 trials in Japan.

Publications

Efficacy, tolerability, and safety of lurasidone for acute schizophrenia: A systematic review and network meta-analysis of phase 3 trials in Japan.

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