GLP-1 and depression concerns have largely been answered by large reviews: the drugs do not appear to raise the risk of depression or suicidal thoughts. In January 2026, FDA reviewed 91 placebo-controlled trials with 107,910 patients and a cohort of more than 2.2 million new users, found no increased risk, and asked that the suicide warning be removed from weight-loss GLP-1 labels.[1] The Wegovy and Zepbound labels now list that warning as removed in February 2026.[2][3]
If you are in crisis in the US, call or text 988, the Suicide and Crisis Lifeline.
For a broader look at mood, appetite and “food noise,” see our guide to Ozempic personality changes. More background is at the GLP-1 basics hub.
Bottom line
| Question | What the evidence says |
|---|---|
| Do GLP-1 drugs increase suicidal thoughts? | No increased risk in FDA’s 2026 trial meta-analysis or its 2.2-million-person Sentinel cohort[1] |
| Do they cause depression? | No increased risk of depression, anxiety or psychosis in FDA’s meta-analysis[1] |
| Do they treat depression? | Not shown; a 72-person trial found no change in depressive symptoms[8] |
| Is there still a label warning? | Removed from Wegovy and Zepbound in February 2026[2][3] |
How the concern started
In 2023, European regulators received reports of suicidal thoughts and self-harm in people taking semaglutide and liraglutide. Case reports like these cannot show cause, but they triggered formal reviews. At the same time, the US weight-loss labels for Wegovy, Saxenda and later Zepbound carried a warning about suicidal behavior and ideation. FDA says that warning came from reports with older weight-loss drugs, not from a GLP-1-specific finding.[1]
What regulators concluded
EMA (April 2024). The EMA’s safety committee, PRAC, reviewed trial data, post-marketing reports and published studies. It concluded that the evidence did not support a causal link between GLP-1 drugs and suicidal thoughts or actions, and that no label update was needed.[4]
FDA (January 2026). FDA’s review had three parts:[1]
- A meta-analysis of 91 placebo-controlled trials (60,338 people on a GLP-1 drug, 47,572 on placebo). It showed no increased risk of suicidal ideation or behavior, and no increased risk of depression, anxiety, irritability or psychosis.
- A Sentinel cohort of 2,243,138 new users from 2015 to 2023, comparing GLP-1 drugs with SGLT2 inhibitors. Intentional self-harm was not more common with GLP-1 drugs.
- Published studies, which FDA found did not support a causal link.
FDA asked makers of Saxenda, Wegovy and tirzepatide (Zepbound) to remove the warning. GLP-1 labels approved only for type 2 diabetes never included it.[1]
2026 label changes
The current Wegovy prescribing information lists “Suicidal Behavior and Ideation (5.10)” as removed in 02/2026.[2] The Zepbound label lists the same warning as removed in 02/2026.[3] We could not confirm the exact date of the Saxenda update, which FDA’s request also covered.
FDA’s patient advice did not change: keep taking the medicine as prescribed, and report new or worsening depression, suicidal thoughts or unusual mood changes to a clinician.[1]
Key studies
STEP trials, pooled (JAMA Internal Medicine, 2024). This post hoc analysis covered 3,377 people in STEP 1, 2 and 3 plus 304 in STEP 5, all without known major psychiatric illness. After 68 weeks, depression scores (PHQ-9) were slightly lower on semaglutide 2.4 mg than placebo. Semaglutide users were less likely to shift to a more severe depression category (odds ratio 0.63). Suicidal thoughts or behavior occurred in 1% or fewer, with no difference between groups.[6]
Suicide and self-harm meta-analysis (JAMA Psychiatry, 2025). Across 27 randomized trials that tracked these events (about 59,000 people), events were very rare: 0.047 per 100 person-years on GLP-1 drugs and 0.042 on placebo. The difference was not statistically significant.[5]
US health-record study (Nature Medicine, 2024). Among 240,618 people with overweight or obesity, semaglutide was linked to a lower risk of new suicidal ideation (hazard ratio 0.27) and repeat suicidal ideation (0.44) than other weight-loss drugs. Results were similar in 1.59 million people with type 2 diabetes.[7]
Semaglutide in major depression (Med, 2026). In 72 adults with major depressive disorder, oral semaglutide did not improve executive function, the main outcome. It did not change depression severity or the frequency of suicidal thoughts. Weight fell by about 6 kg more than placebo.[8]
What’s established vs preliminary
Established:
- No increased risk of suicidal thoughts, depression or anxiety at the population level.[1][5]
- The weight-loss labels no longer carry the suicide warning.[2][3]
Preliminary:
- Whether GLP-1 drugs might lower depression or suicide risk. Observational signals exist, but healthier or better-supported people may be more likely to get these drugs.[7]
- Effects in people with current major depression, bipolar disorder or eating disorders.
Limitations
- Rare events. Suicide attempts are uncommon, so even large trials have few events to compare.[5]
- Excluded groups. Many weight-loss trials left out people with recent major depression or suicide attempts.[6]
- Observational bias. Health-record studies can’t fully adjust for who gets prescribed these drugs.
- Individual reactions. A population average doesn’t rule out mood changes in a single person. Rapid weight loss, nausea, poor sleep or stopping a drug can all affect how people feel. Our page on GLP-1 fatigue covers one common contributor.
What’s next
A Danish phase 4 trial is testing whether semaglutide improves depressive symptoms in 116 adults with major depressive disorder and overweight or obesity, with primary completion planned for September 2027.[9]
Questions to discuss with a clinician
- Given my mental health history, how should we monitor my mood after I start?
- Could nausea, low food intake or poor sleep be affecting how I feel?
- How do my antidepressants or other psychiatric medicines fit with a GLP-1?
- What should I do if I notice changes in pleasure, motivation or mood? Related research on cravings is in our page on GLP-1 drugs and emotional eating.
