Safety and efficacy of different initial doses of lurasidone in the schizophrenia treatment: A multi-center, randomized, open-label study

Abstract

BACKGROUND

Schizophrenia, a complex group of mental disorders, is primarily managed with antipsychotic medications. The safety and efficacy of different initial doses of lurasidone for acute schizophrenia remain uncertain, particularly concerning discontinuation rates due to adverse events (AEs).

AIM

To compare the safety of two initial doses of lurasidone for the treatment of acute schizophrenia in Chinese patients.

METHODS

This 6-week, randomized, open-label, multicenter trial allocated participants to receive either 40 mg/day or 80 mg/day lurasidone initially, with dose adjustment allowed after a one-week fixed-dose period. Safety assessments included the primary endpoint of discontinuation due to AEs, as well as evaluations of AEs, weight changes, and laboratory parameters. Efficacy assessments included responder rates and changes in scores on the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Severity scale, and Calgary Depression Scale for Schizophrenia.

RESULTS

Among 197 participants, no significant difference was found in discontinuation rate due to AEs between groups (3.03% vs 5.10%, P = 0.707). Treatment-emergent AEs were reported in 64.6% and 71.4% of participants in the 40 mg/day and 80 mg/day initiation groups, respectively. Response rates at weeks 1 and 2 showed no statistically significant differences. Both groups demonstrated significant improvements in PANSS total, Clinical Global Impression-Severity, and Calgary Depression Scale for Schizophrenia scores from baseline (all P < 0.01). Notably, the 80 mg/day initiation group showed greater improvement in the PANSS positive subscale score at visits 1 and 2 compared to the 40 mg/day initiation group (P < 0.05).

CONCLUSION

Initial doses of 40 mg/day and 80 mg/day lurasidone are safe and effective for acute schizophrenia, with no significant increase in AEs-related discontinuation rate at the higher dose.

Keywords: Schizophrenia; Discontinuation rate; Efficacy; Safety; Lurasidone

Core Tip: This randomized, multicenter study innovatively compares initial lurasidone doses (40 mg/day vs 80 mg/day) in Chinese patients with acute schizophrenia, addressing a critical gap in dose optimization. Key findings reveal no significant difference in discontinuation rates due to adverse events (3.03% vs 5.10%, P = 0.707), affirming the tolerability of higher initial dosing. Notably, the 80 mg/day group showed superior early improvement in Positive and Negative Syndrome Scale positive subscale scores (P < 0.05) without exacerbating metabolic risks. These results challenge conventional dosing paradigms, suggesting 80 mg/day as a viable initial option for rapid symptom control, while maintaining safety.