Comparative Efficacy and the Muscarinic Breakthrough: A Comprehensive Network Meta-Analysis of Antipsychotic Interventions for Acute Schizophrenia

Highlights

The following key findings emerge from this comprehensive network meta-analysis (NMA) of pharmacological interventions for acute schizophrenia:

  • Clozapine remains the most efficacious antipsychotic for symptom reduction, followed by amisulpride, olanzapine, and risperidone, though confidence in these estimates ranges from low to moderate.
  • All 24 studied antipsychotics demonstrated superior efficacy compared to placebo, with standardized mean differences (SMD) ranging from -0.90 to -0.23.
  • The 2024-licensed muscarinic receptor agonist, xanomeline-trospium, provides a novel therapeutic pathway that avoids traditional dopamine-related adverse effects but introduces unique cholinergic and anticholinergic profiles.
  • Partial dopamine agonists generally exhibited the most favorable overall tolerability profiles among the antidopaminergic class.
  • The study highlights the necessity of updating clinical guidelines to reflect small-to-medium clinically relevant differences in efficacy between specific antipsychotic agents.

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