Abstract
BACKGROUND: Schizophrenia is a group of serious mental illnesses and antipsychotics are the primary clinical treatment. Lurasidone, a second-generation antipsychotic drug, was approved in China in 2019 for the treatment of adult schizophrenia with a maximum dose of 80 mg/d. The safety and efficacy of different initial doses of lurasidone in treating acute schizophrenia remain unclear, especially whether the discontinuation rate due to adverse events (AEs) increases with higher initial dose. AIM: To compare the safety and efficacy of different initial doses of lurasidone in the treatment of acute schizophrenia. METHODS: A 6-week, randomized, open-label, multi-center study was conducted and eligible subjects were randomized to receive either a 40 mg/d or 80 mg/d initial dose of lurasidone in a 1:1 ratio. The dose could be adjusted or maintained after 7 days of fixed-dose initial treatment. The primary safety endpoint was the discontinuation rate due to AEs at the end of treatment. Other safety evaluations included adverse events, weight change and laboratory tests. The efficacy was assessed by the proportion of responders at week1/ week2 and changes in PANSS total score and Lindenmayer 5-factor scores / Clinical Global Impression-Severity (CGI-S) scale score/ Calgary Depression Scale for Schizophrenia (CDSS) score from baseline to week 6. RESULTS: A total of 197 patients were enrolled in the full analysis set (FAS) and the safety set (SS). There was no significant difference in the discontinuation rate due to AEs between the two treatment groups (3.03% in 40 mg/d initiation group vs 5.10% in 80 mg/d initiation group, P = 0.707). 193 AEs occurred in 65 subjects (65.7%) in 40 mg/d initiation group and 185 AEs occurred in 71 subjects (72.4%) in 80 mg/d initiation group. Notably, the 40 mg/d initiation group had a higher percentage of patients experiencing clinically significant weight gain compared to the 80 mg/d initiation group (12.1% vs 4.1%). The proportion of responders was similar between the two groups at week 1 (39.39% vs 40.82%, P = 0.839) and showed a numerical, but not statistically significant advantage for the 80 mg/d initiation group at week 2 (52.53% vs 57.14%, P = 0.515). Compared to the baseline, significant improvements were observed in the PANSS total score (P <0.001) and 5-factor scores (P <0.001), CGI-S scale score (P <0.001), and CDSS score (P <0.01) at all visit points in both treatment groups. Additionally, treatment with 80 mg/d initial dose of lurasidone was associated with significantly greater improvement on 5- factor cognitive score at visit 2-4 compared to the 40 mg/d initial dose. CONCLUSION: Both the 40 mg/d or 80 mg/d initial doses of lurasidone are safe and effective for the treatment of acute schizophrenia. Furthermore, the 80 mg/d initial dose does not result in a significantly higher discontinuation rate due to AEs compared to the 40 mg/d initial dose. REFERENCES: 1.Jingping Z., et al., Guidelines for schizophrenia Prevention and Treatment in China (2nd Edition). 2015. 2.Yumei W., et al., Safety and effectiveness of lurasidone in the treatment of Chinese schizophrenia patients: An interim analysis of post-marketing surveillance. World J Psychiatry. 2023.