Neuropsychiatric Effects of Glucagon-Like Peptide-1 Receptor Agonists in Schizophrenia-Spectrum Disorders: A Systematic Review
Abstract
People with schizophrenia-spectrum disorders die 15-20 years prematurely, predominantly from cardiovascular disease, and antipsychotic-induced weight gain is a major, partly iatrogenic contributor to this excess mortality. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are potent weight-lowering agents that are increasingly used as metabolic adjuncts in this population, and preclinical evidence has suggested that they may also exert central, potentially pro-cognitive effects. However, their effects on psychiatric symptoms, cognition, and quality of life have not previously been systematically synthesized. We therefore conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Four databases (MEDLINE/PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science) were searched on 20 July 2026 for randomized controlled trials (RCTs) comparing any GLP-1RA with placebo, usual care, or an active comparator, added to antipsychotic treatment, in adults with schizophrenia-spectrum disorders. The primary outcome was psychiatric symptom severity, while secondary outcomes were cognition and quality of life or functioning. Reports were de-duplicated at the trial level using trial registration records, and risk of bias was assessed for each outcome domain using the revised Cochrane Risk of Bias tool for randomized trials (RoB 2). Because outcome measures were heterogeneous and…
How strong is the evidence?
Evidence Hub reads this as a systematic review, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 333 participants or records.
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