{
  "abstract": "Neuropsychiatric safety concerns about glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and tirzepatide prompted regulatory review by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). We synthesized the contemporary evidence in adults with type 2 diabetes mellitus or obesity, emphasizing study design, risk of bias, and the distinction between signal detection and causal inference. The PubMed/MEDLINE, Embase, Web of Science, and Scopus databases were searched without a lower date limit through March 15, 2026 (English, adults ≥18 years). The review was reported with reference to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020, and the PRISMA-S and PRISMA-Harms extensions. Evidence was grouped into prespecified categories: randomized syntheses, comparative observational studies and target-trial emulations, outlier non-active-comparator studies, pharmacovigilance analyses, and regulatory reviews. Risk of bias was appraised with the Cochrane Risk of Bias 2 tool and with Risk of Bias in Non-randomised Studies of Interventions; certainty was summarized using Grading of Recommendations Assessment, Development and Evaluation. Twenty studies and two regulatory reviews met the inclusion criteria. Randomized evidence, including two large 2025 meta-analyses and post hoc pooled analyses of semaglutide and tirzepatide, showed no increased risk of suicidality, depression, or anxiety, though psychiatric exclusion criteria limited generalizability. Active-comparator cohorts from the United States, Scandinavia, and the United Kingdom likewise showed no clear increase after confounding control. Passive-comparator and disproportionality analyses generated signals but could not separate drug effects from baseline psychiatric risk, obesity-related distress, or reporting bias. The EMA and FDA conclusions do not support a causal class-wide association between GLP-1 RAs and suicidal ideation or behavior. Evidence does not support a clinically meaningful increase in neuropsychiatric harm with GLP-1 RAs or tirzepatide in the populations studied. Surveillance remains warranted for patients with substantial psychiatric morbidity, for obesity-only populations, and for long-term rare outcomes.",
  "abstract_shown": true,
  "affiliations": [
    "Master of Public Health Program, Long Island University, Brooklyn, New York, USA.",
    "Frank H. Netter MD School of Medicine, Quinnipiac University, North Haven, Connecticut, USA.",
    "St. Vincent's Medical Center, Hartford HealthCare, Bridgeport, Connecticut, USA."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Het Tushar Jani"
    },
    {
      "affs": [
        0
      ],
      "name": "Helisse Levine"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Abhiraj Patel"
    },
    {
      "affs": [
        0
      ],
      "name": "Richa Trivedi"
    },
    {
      "affs": [
        0
      ],
      "name": "Xitij Dineshkumar Patel"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/176dghz46h1r8.bib",
  "cited_by": 0,
  "doi": "10.5041/rmmj.10585",
  "fulltext_url": "https://europepmc.org/articles/PMC13719276",
  "id": "176dghz46h1r8",
  "issns": [
    "2076-9172"
  ],
  "landing_url": "https://europepmc.org/article/MED/42957176",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review Article"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://europepmc.org/articles/PMC13719276?pdf=render",
  "pmcid": "PMC13719276",
  "pmid": "42957176",
  "published": "2026-10-26",
  "publisher": "Rambam Health Care Campus",
  "ris": "https://research.draconitic.com/paper/176dghz46h1r8.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:40Z",
      "native_id": "MED:42957176",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42957176"
    },
    {
      "first_seen": "2026-11-02T12:23:08Z",
      "native_id": "PMC13719276",
      "source": "pmc",
      "url": "https://doi.org/10.5041/rmmj.10585"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "journal-openalex:F27",
      "subfield": "general"
    }
  ],
  "title": "Neuropsychiatric Safety of GLP-1 Receptor Agonists and Tirzepatide in Adults with Type 2 Diabetes Mellitus or Obesity.",
  "title_text": "Neuropsychiatric Safety of GLP-1 Receptor Agonists and Tirzepatide in Adults with Type 2 Diabetes Mellitus or Obesity.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:23:08Z",
  "url": "https://research.draconitic.com/paper/176dghz46h1r8",
  "venue": "Rambam Maimonides medical journal",
  "versions": []
}