Psychiatr Q. 2026 Aug 3. doi: 10.1007/s11126-026-10303-5. Online ahead of print.
ABSTRACT
This letter addresses significant methodological limitations in a recently published systematic review and meta-analysis evaluating the efficacy and safety of xanomeline-trospium (KarXT) in schizophrenia. A critical unit-of-analysis error is identified in the original review’s Table 1, wherein multiple secondary and post hoc publications from a single randomized controlled trial (EMERGENT-1) were extracted and treated as completely independent studies. This unit-of-analysis error violates statistical independence assumptions and likely contributed to an implausible pooled effect size; however, additional discrepancies in data extraction or effect-size calculation may also have influenced the pooled estimate (d = 0.08) that sharply contradicts individual trial data. Additionally, the review lacks registered protocol details, structured risk-of-bias reporting, and safety outcome pooling. Readers and clinicians are cautioned against interpreting the pooled conclusions in isolation.
PMID:42543467 | DOI:10.1007/s11126-026-10303-5
