⚠️ Signal Detected — No Causal Link Established
FDA and EMA concluded their investigations without finding causation. Some pharmacovigilance studies suggest monitoring is warranted.
📞 If You're Struggling
If you or someone you know is experiencing suicidal thoughts or mental health crisis, please call the 988 Suicide & Crisis Lifeline by dialing 988, or visit 988lifeline.org.
The Conflicting Evidence
The question of whether GLP-1 drugs like semaglutide cause depression or suicidal thoughts has produced genuinely conflicting evidence. Different data sources point in different directions:
✓ Evidence Against a Link
Nature Medicine (January 2024): Large NIH-backed study of 240,618 patients found semaglutide associated with 73% lower risk of first-time suicidal ideation and 56% lower risk of recurrent suicidal ideation vs. other anti-obesity medications.
STEP Trial Post-Hoc Analysis (2024): Patients taking semaglutide were not at higher risk for developing depression or suicidal thoughts compared to placebo.
Adolescent Data: Semaglutide groups showed lower rates of psychiatric adverse events (7%) than placebo (15%).
⚠️ Evidence Suggesting Monitoring
WHO Database Analysis (JAMA Network Open, August 2024): Found "disproportionate" reporting of suicidal ideation for semaglutide compared to liraglutide. 107 reports out of 30,500+ total.
FAERS Analysis (June 2025): Significant signals identified for semaglutide in depression (ROR 1.87) and suicide/self-injury events (ROR 1.73). Effects most pronounced in ages 18-64.
Trend: Reporting increased over recent years, possibly due to expanded use in weight management.
✗ Regulatory Investigations Found No Causation
FDA (January 2024): "Our preliminary evaluation has not found evidence that use of these medicines causes suicidal thoughts or actions."
EMA (April 2024): Concluded there was "no evidence to support a causal association between GLP-1 receptor agonists and suicidal and self-injurious thoughts and actions."
Caveat: FDA noted it "cannot definitively rule out that a small risk may exist" due to small event numbers. Investigation ongoing.
Understanding the Data Sources
FAERS (FDA Adverse Event Reporting System)
FAERS is a self-reporting system—anyone can submit a report. A report doesn't mean the drug caused the event. Key limitations:
- Reports are not verified or investigated individually
- Information is often incomplete
- Reporting rates increase with media attention
- Cannot establish causation—only signals for further investigation
Controlled Clinical Trials
Clinical trials (STEP, SUSTAIN, etc.) showed no increased psychiatric adverse events with semaglutide vs. placebo. However, trials may exclude patients with psychiatric history, limiting generalizability.
Real-World Cohort Studies
The Nature Medicine study used 100+ million patient records and found semaglutide users had lower rates of suicidal ideation than those on other medications for the same conditions.
Regulatory Timeline
Why the Confusion?
Several factors complicate interpretation:
1. Obesity Itself Is Linked to Depression
People with obesity have higher baseline rates of depression and suicidal ideation. Separating drug effects from underlying condition effects is challenging.
2. Rapid Weight Loss Effects
Significant body changes can affect mood and self-image. Previous weight loss drugs (like rimonabant) were pulled for psychiatric side effects—researchers are appropriately cautious.
3. Confounding Medications
WHO database analysis found suicidal ideation reports were more common in patients already taking anxiety or depression medications—suggesting pre-existing psychiatric conditions.
4. Reporting Bias
As GLP-1 drugs received massive media attention, adverse event reporting increased. This may reflect increased scrutiny rather than increased risk.
5. Different Drug Comparisons
When comparing semaglutide to liraglutide in the WHO database, semaglutide showed a signal. But when comparing to non-GLP-1 medications in the Nature Medicine study, semaglutide showed lower risk. The comparator matters.
What the June 2025 FAERS Study Found
The most recent pharmacovigilance analysis (Xu et al., June 2025) analyzed FAERS data from 2004-2024:
- Semaglutide: Significant signal for depression (ROR 1.87) and suicide/self-injury (ROR 1.73)
- Liraglutide: No significant signal
- Tirzepatide: No significant signal; significantly lower mortality rate (0.26%) than other agents
- Demographics: Effects most pronounced in ages 18-64
- Timing: Increased reporting after weight management approval (vs. diabetes-only indication)
The authors suggest tirzepatide "may represent a more appropriate choice" for patients with psychiatric comorbidities based on its superior safety profile in this analysis.
What Should Patients Do?
Patient information for semaglutide already includes a warning to watch for depression and suicidal thoughts. Tell your healthcare provider about any new or worsening depression, suicidal thoughts, or unusual changes in mood or behavior.
Specific recommendations:
- Disclose psychiatric history to your prescriber before starting GLP-1 treatment
- Monitor mood throughout treatment, especially during dose changes
- Report symptoms promptly—don't wait for your next scheduled appointment
- Don't stop abruptly—work with your provider on any medication changes
- Consider tirzepatide if you have significant psychiatric history (discuss with provider)
The Bottom Line
The evidence is genuinely mixed:
- Controlled trials: Show no increased risk
- Large real-world study: Shows lower risk with semaglutide vs. comparators
- Pharmacovigilance databases: Show increased reporting (signal) for semaglutide
- Regulatory conclusions: No causal link established
The scientific consensus is that GLP-1 drugs don't appear to cause depression or suicidality at a population level. However, individual responses vary, and patients with pre-existing psychiatric conditions may need closer monitoring.
As one researcher put it: "This pharmacovigilance signal is like an early warning system and should not be immediately viewed as an alarm."
Sources
- Wang W, et al. "Association of semaglutide with risk of suicidal ideation in a real-world cohort." Nature Medicine. January 2024;30(1):168-176.
- Schoretsanitis G, et al. "Disproportionality Analysis From World Health Organization Data on Semaglutide, Liraglutide, and Suicidality." JAMA Network Open. August 2024;7(8):e2423385.
- FDA. "Update on FDA's ongoing evaluation of reports of suicidal thoughts or actions in patients taking a certain type of medicines approved for type 2 diabetes and obesity." FDA.gov. January 2024.
- European Medicines Agency. "No evidence that GLP-1 receptor agonists cause suicidal thoughts or actions." EMA.europa.eu. April 2024.
- "Depression and suicide/self-injury signals for weight loss medications: A disproportionality analysis of semaglutide, liraglutide, and tirzepatide in FAERS database." Journal of Affective Disorders. June 2025.
- CNN. "A study linking popular weight loss drug to suicide risk again raises long-standing safety questions." CNN. August 2024.
- CNN. "Ozempic, Wegovy not associated with higher risk of suicidal ideation in large review of US health records." CNN. January 2024.
- TCTMD. "'Disproportionate' Suicide/Self-Harm Signal With Semaglutide: WHO Database." TCTMD. July 2025.
- Drugs.com. "Can Ozempic cause personality changes or depression?" Drugs.com. August 2025.
- WHSV. "FDA receives patient reports of depression, suicide after taking weight loss drugs." WHSV. April 2024.
- FDA FAERS Database. Accessed 2025.
- STEP Clinical Trials Program post-hoc analyses.
Explore More GLP-1 Research
We cover every major study with full source documentation.
Browse All Articles →