Liu Q, Qian MC, Liu ZF, Dong F, Liu DT, Li ML, Ning YP, Wang XP, Liu TB, Wu Q, Li T, Yu X. Safety and efficacy of different initial doses of lurasidone in the schizophrenia treatment: A multi-center, randomized, open-label study. World J Psychiatry 2025; 15(10): 110968 [PMID: 41112599 DOI: 10.5498/wjp.v15.i10.110968]
Reader's ID:
08200676
Submitted on:
October 01, 2025, 00:48
Reader Expertise:
Reader’s expertise on the topic of the manuscript
Conflicts-of-Interest Statement:
Does the reader have a conflict of interest?
Reader Comment Standards for Published Articles:
1 Title
Does the title reflect the main subject/hypothesis of the manuscript?
2 Abstract
Does the abstract summarize and reflect the work described in the manuscript?
3 Key Words
Do the key words reflect the focus of the manuscript?
4 Background
Does the manuscript adequately describe the background, present status and significance of the study?
5 Methods
Does the manuscript describe methods (e.g., experiments, data analysis, surveys, and clinical trials, etc.) in adequate detail?
6 Results
Are the research objectives achieved by the experiments used in this study?
Has the study made meaningful contributions towards research progress in this field?
7 Discussion
Does the manuscript interpret the findings adequately and appropriately, highlighting the key points concisely, clearly and logically?
Are the findings and their applicability/relevance to the literature stated in a clear and definite manner?
Is the Discussion accurate and does it discuss the paper’s scientific significance and/or relevance to clinical practice sufficiently?
8 Illustrations and Tables
Are the figures, diagrams and tables sufficient, good quality and appropriately illustrative of the paper contents?
Do figures require labeling with arrows, asterisks, etc., or better legends?
9 Biostatistics
Does the manuscript meet the requirements of biostatistics?
10 Units
Does the manuscript meet the requirements of use of SI units?
11 References
Does the manuscript appropriately cite the latest, important and authoritative references in the Introduction and Discussion sections?
Does the author self-cite, omit, incorrectly cite and/or over-cite references?
12 Quality of manuscript organization and presentation
Is the manuscript concisely and coherently organized and presented?
Are the style, language and grammar accurate and appropriate?
13 Ethics statements
For all manuscripts involving human studies and/or animal experiments, author(s) must submit the related formal ethics documents that were reviewed and approved by their local ethical review committee. Did the manuscript meet the requirements of ethics?
Scientific Quality:
The overall quality of the manuscript, based on the above-listed criteria, should be evaluated and classified according to the following five categories
Language Quality:
Language quality (style, grammar, and spelling) should be evaluated and classified according to the following five categories.
Reader Comments:
After reading with great interest the recent article by Liu et al. (2025) comparing the safety and efficacy of 40 mg/day and 80 mg/day initial doses of lurasidone in acute schizophrenia. The study addresses a clinically relevant question regarding optimal dosing strategies, particularly in Chinese populations where approved doses may differ from international guidelines.
The authors should be commended for their pragmatic trial design, which incorporated a one-week fixed-dose period followed by flexible dosing—a approach that closely mirrors real-world clinical practice. The finding of no significant difference in discontinuation rates due to adverse events (3.03% vs 5.10%, P=0.707) between the two dosing strategies provides valuable evidence supporting the safety of initiating treatment at 80 mg/day.
Several aspects of the results deserve particular attention. The early advantage in PANSS positive subscale improvement observed in the 80 mg/day group at weeks 1 and 2 (P<0.05) suggests that higher initial dosing may offer more rapid control of psychotic symptoms—a potentially important consideration in acute care settings. Equally noteworthy was the paradoxical finding regarding weight change, with the 40 mg/day group showing significant weight gain (0.83 kg, P<0.01) compared to minimal change in the 80 mg/day group (-0.08 kg). This observation challenges conventional dose-response expectations and warrants further investigation.
However, some limitations should be considered when interpreting these findings. The open-label design, while pragmatic, introduces potential for assessment bias. Additionally, the relatively short 6-week duration limits understanding of long-term outcomes, and the sample size, though adequate for safety endpoints, may be underpowered for certain efficacy comparisons.
Despite these limitations, this study makes a valuable contribution to the literature by demonstrating that 80 mg/day initiation appears to be a viable and safe option that may offer early symptomatic benefits without increased metabolic risk. These findings should encourage clinicians to consider individual patient needs when selecting initial doses, particularly when rapid symptom control is prioritized.
Future research with longer follow-up and broader dose ranges would help further elucidate the optimal dosing strategies for lurasidone in diverse clinical populations.