Comparative Efficacy, Safety, and Tolerability of KarXT versus Eight Atypical Antipsychotics for the Acute Treatment of Adults with Schizophrenia – A Network Meta-Analysis

Objectives:
To expand prior network meta-analyses investigating the relative efficacy, safety, and tolerability of xanomeline and trospium (KarXT), for the acute treatment of schizophrenia.1

Methods:
An updated systematic literature review (SLR) was undertaken, building on a 2019 SLR,2 to identify RCTs of nine oral antipsychotics for acute treatment of adults with schizophrenia. Our SLR identified new publications from January 1st 2019 to March 20th 2024 and re-evaluated previously identified records against new inclusion criteria.

Bayesian NMAs were conducted for eleven outcomes: clinical response (≥30% decrease in Positive and Negative Syndrome Scale [PANSS] total score), all-cause discontinuation, discontinuation due to adverse events, sedation, somnolence, clinically significant weight gain (≥7% increase), change from baseline (CFB) PANSS scores (total, positive symptoms, and negative symptoms), CFB Clinical Global Impressions – Severity (CGI-S) score, and CFB weight.

Results:
KarXT treatment significantly improved odds of clinical response versus aripiprazole (odds ratio [OR]: 1.85; 95% credible interval [CrI]: 1.11, 3.11), brexipiprazole (OR: 2.23; 95% CrI: 1.34, 3.83), and cariprazine (OR: 2.05; 95% CrI: 1.19, 3.57), increased odds of all-cause discontinuation versus all comparators except cariprazine, and reduced odds of clinically significant weight gain versus aripiprazole, brexipiprazole, cariprazine, lumateperone, olanzapine, quetiapine, and risperidone. Further favorable results for KarXT included improvements in: CFB CGI-S versus aripiprazole, brexpiprazole, cariprazine, and olanzapine, CFB PANSS positive symptoms score versus brexpiprazole, and CFB weight versus brexiprazole, clozapine, olanzapine, quetiapine, and risperidone.

Conclusion:
KarXT demonstrated improved clinical response and reduced weight gain compared with several existing oral antipsychotics.