A 6-week, double-blind, placebo- and haloperidol-controlled, phase II study of lurasidone in patients with acute schizophrenia

Abstract

Objective: The objective of this study was to evaluate the short-term efficacy and safety of the atypical antipsychotic agent lurasidone in the treatment of schizophrenia. Methods: In this phase II, randomized, double-blind, placebo-controlled study, hospitalized adult patients diagnosed with schizophrenia and experiencing an acute exacerbation of psychotic symptoms were randomly assigned to 6 weeks of fixed-dose lurasidone 20 mg/day ( n = 71), lurasidone 40 mg/day ( n = 67), lurasidone 80 mg/day ( n = 71), haloperidol 10 mg/day ( n = 72, included to test for assay sensitivity), or placebo ( n = 72). Efficacy was assessed using the brief psychiatric rating scale, positive and negative syndrome scale, and clinical global impression-severity. Safety assessments included incidence of adverse events and clinical laboratory measures. Results: Numerical improvement was observed from baseline to week 6 (last observation carried forward) on all efficacy measures in all treatment groups; however, no statistically significant differences were noted between any lurasidone group and placebo, or between haloperidol and placebo. The most common adverse events in lurasidone-treated patients, with an incidence of at least 10% (dose groups combined) and greater than placebo, were sedation (15.3%), dyspepsia (13.4%), nausea (13.4%), akathisia (12.4%), and vomiting (10.5%); for haloperidol, the most common adverse events (incidence ⩾ 10% and greater than placebo) were extrapyramidal disorder (20.8%), sedation (19.4%), akathisia (19.4%), dystonia (15.3%), insomnia (13.9%), and somnolence (12.5%). Lurasidone was associated with minimal changes in weight, metabolic parameters, and prolactin levels. Conclusions: None of the lurasidone groups separated from placebo in this clinical study of patients with acute schizophrenia. In addition, haloperidol, which was included for assay sensitivity, did not separate from placebo, resulting in a failed study. Possible reasons for the lack of assay sensitivity in this study include the use of multiple active treatment arms and the relatively large placebo response. Consistent with other studies, lurasidone was generally safe and well tolerated, with minimal effects on weight or metabolic parameters.

Akathisia and Newer Second‐Generation Antipsychotic Drugs: A Review of Current Evidence

“…A total of 177 studies with 58,069 participants across 414 treatment arms were included in the comparative analysis (Appendix ) 32–111 . Of these, the breakdown for numbers of studies including each medication are aripiprazole (88), asenapine (10), brexpiprazole (8), cariprazine (10), iloperidone (6), lurasidone (14), paliperidone (9), risperidone (25), and ziprasidone (11).…”

Neurobiological mechanisms associated with antipsychotic drug-induced dystonia

“…Empirically, both acute and tardive forms are relatively scarce and unpredictable, which makes it difficult to prospectively select a patient population containing enough persons who will eventually experience such phenomena. For example, in a placebo- and haloperidol-controlled clinical trial of an antipsychotic drug in the treatment of 353 patients experiencing an acute exacerbation of schizophrenia conducted at 33 sites in the USA between August 2002–May 2003, only 16 patients (4.5%) suffered from dystonia (Potkin et al, 2015). Apart from their limited number, the geographical spread incapacitates practically the ability to rapidly include these patients in sophisticated experimental studies once dystonia has occurred.…”

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

“…We further assessed 15 full-text publications and excluded five trials, including two flexible-dose trials 27,28 , one 3-week trial 29 , one trial in adolescent patients 30 , and one trial in adults with treatment-resistant schizophrenia 31 . Finally, ten RCTs were included for network meta-analysis [6][7][8][9][32][33][34][35][36][37] .…”