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Glucagon-Like Peptide-1 Receptor Agonists for Mood Disorders and Suicide Risk

Roger S McIntyre1

  • 1Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.

Biological Psychiatry
|May 2, 2026
PubMed

Insights

Glucagon-like peptide-1 receptor agonists show promise for treating mood disorders like depression and bipolar disorder. Further clinical studies are warranted to explore their efficacy and mechanisms, including effects on anhedonia and cognitive impairment.

Area of Science:

  • Neuroscience
  • Psychiatry
  • Pharmacology

Background:

  • Mood disorders require novel therapeutics with improved efficacy, tolerability, and faster onset.
  • Current treatments inadequately address pervasive symptoms like anhedonia and cognitive impairment.
  • Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are emerging as potential mood disorder treatments.

Purpose of the Study:

  • To evaluate the potential of GLP-1 RAs as mechanistically-informed therapeutics for mood disorders.
  • To explore the neurobiological mechanisms underlying GLP-1 RA action in mood disorders.
  • To advocate for well-controlled clinical studies of GLP-1 RAs in major depressive disorder and bipolar disorder.

Main Methods:

  • Review of preclinical, translational, observational, and clinical data on GLP-1 RAs in mood disorders.
  • Analysis of proposed mechanisms of action, including metabolic and direct neural effects.
  • Assessment of existing evidence for efficacy and tolerability in mood disorder populations.

Main Results:

  • GLP-1 RAs exhibit potential therapeutic benefits through various mechanisms, including neuroplasticity and neuroprotection.
  • Evidence supports the initiation of clinical trials for major depressive disorder and bipolar disorder.
  • Preliminary data suggests GLP-1 RAs may improve reward pathways and potentially impact suicidality, though causality is not established.

Conclusions:

  • GLP-1 RAs represent a promising class of therapeutics for mood disorders, targeting unmet clinical needs.
  • Further rigorous clinical investigation is essential to confirm efficacy, optimize use, and elucidate mechanisms.
  • GLP-1 RAs may offer benefits for specific symptom domains, including those related to reward and suicidality.
Keywords:
BipolarDepressionGLP-1Glucose-dependent insulinotropic polypeptide (GIP)SemaglutideSuicidality

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