GLP-1 Drugs Like Semaglutide Linked to Depression and Suicidal Thoughts in Adverse Event Databases | Research

The takeaway

Analysis of three national adverse event databases found semaglutide was significantly associated with depression, panic attacks, and suicidal ideation, while other GLP-1 drugs showed links to eating disorders and insomnia.

ROR 6.24 for depression
Semaglutide had over 6 times the expected reporting rate for depressive symptoms in the US FAERS database

What the researchers found

Semaglutide showed the strongest psychiatric safety signals: depressive symptoms (ROR = 6.24, CI 4.49–8.69 in FAERS), suicidal ideation (ROR = 2.58, CI 2.31–2.88 in FAERS), and panic attacks (ROR = 1.46, CI 1.16–1.82 in FAERS). Liraglutide was linked to depression in the Canadian database (ROR = 1.68, CI 1.12–2.51). Dulaglutide was associated with eating disorders (ROR = 1.47, CI 1.26–1.71) and insomnia (ROR = 2.93, CI 2.35–3.66) in FAERS.

Significant associations were identified when multiple databases showed elevated reporting odds ratios, strengthening the signal reliability.

Why it matters

With tens of millions of people now taking GLP-1 drugs for diabetes and weight loss, understanding psychiatric risks is urgent. If semaglutide truly elevates suicide risk even modestly, the public health implications are enormous given the scale of use. These findings reinforce the need for psychiatric monitoring in patients starting these medications.

How the study worked

This pharmacovigilance study extracted psychiatric adverse event reports for all approved GLP-1 analogues from three national databases: FAERS (US), CVAROD (Canada), and DAEN (Australia). Disproportionality analysis was used to calculate reporting odds ratios (RORs) with 95% confidence intervals, comparing psychiatric event reporting rates for GLP-1 drugs against all other drugs in each database.

What this study cannot tell us

Disproportionality analysis of adverse event databases can identify safety signals but cannot prove causation. Reporting biases are significant — high media attention on GLP-1 drugs may increase psychiatric event reporting (stimulated reporting). The databases lack denominator data (total prescriptions), so true incidence rates cannot be calculated. Patient-level confounders like pre-existing psychiatric conditions, obesity, and diabetes are not controlled for.

How to read the evidence

This is a pharmacovigilance disproportionality analysis — a signal-detection method, not a causal study. While the use of three independent national databases strengthens the signal, reporting biases and confounders limit the conclusions. It represents moderate-level safety signal evidence.

When this study was published

Published in 2025, this study addresses one of the most timely safety questions in medicine given the rapid global uptake of GLP-1 drugs for diabetes and obesity.

The bigger picture

The psychiatric safety of GLP-1 receptor agonists has become one of the most debated topics in pharmacology as prescription rates have soared. The European Medicines Agency has already reviewed suicidality signals for this drug class. This multi-database analysis adds substantial evidence to the concern, though the fundamental question — whether GLP-1 drugs cause psychiatric effects or are simply used more by people already at risk — remains unanswered.

Questions still open

Do GLP-1 receptor agonists directly affect brain circuits involved in mood and suicidality, or are these associations driven by confounding factors?
Should patients with pre-existing depression or suicidal ideation be screened more carefully before starting GLP-1 drugs?
Why does semaglutide show stronger psychiatric signals than other GLP-1 drugs — is it a dose effect, brain penetration, or reporting bias?

Common questions

Does this mean semaglutide causes depression or suicidal thoughts?

Not necessarily. This study found that depression and suicidal ideation are reported more often with semaglutide than expected in adverse event databases, but it cannot prove the drug causes these effects. The association could be influenced by reporting biases, media attention, or the fact that people taking these drugs may already have risk factors for depression.

Should I stop taking my GLP-1 medication because of these findings?

Do not stop any medication without consulting your doctor. If you experience new or worsening depression, anxiety, or thoughts of self-harm while taking a GLP-1 drug, contact your healthcare provider promptly. They can help assess whether the medication may be contributing and discuss alternatives.

Read the original research

Psychiatric adverse events linked to glucagon-like peptide 1 analogues: a disproportionality analysis in American, Canadian and Australian adverse event databases.

International journal of clinical pharmacy, 47(6), 1739-1747

View on PubMed ↗Publisher’s paper ↗

Citation

Katranski, Jonah; Liang, Sihua; Morris, Deirdre; Suppiah, Vijayaprakash; Lim, Chiao Xin. (2025). Psychiatric adverse events linked to glucagon-like peptide 1 analogues: a disproportionality analysis in American, Canadian and Australian adverse event databases.. International journal of clinical pharmacy, 47(6), 1739-1747. https://doi.org/10.1007/s11096-025-01943-x