Three things changed in 2026 that most pages on this question have not caught up with: the FDA asked for the suicidal-thoughts warning to be taken off the GLP-1 weight-loss labels, the labels were rewritten, and a new oral GLP-1 was approved without the warning at all. This page reads the current labels, the FDA and European reviews, and the one trial analysis that measured depression directly, as of 27 September 2026 — and sets out what that evidence did not test.
For the rest of the side-effect record see GLP-1 side effects; for tiredness specifically, fatigue on GLP-1s; for what these drugs are being studied for in the brain, GLP-1 and cognition.
What the labels say now
| Label (current version) | Molecule | Use | Suicidal behavior and ideation warning |
|---|---|---|---|
| Wegovy (June 2026) | semaglutide | weight | Removed 02/2026 (was section 5.10) |
| Zepbound (August 2026) | tirzepatide | weight | Removed 02/2026 |
| Saxenda (February 2026) | liraglutide | weight | Removed 02/2026 (was section 5.9) |
| Foundayo (July 2026) | orforglipron | weight | Not present |
| Ozempic, Mounjaro | semaglutide, tirzepatide | diabetes | Never carried it |
| Qsymia (April 2026) | phentermine/topiramate | weight | Still present — monitor for depression or suicidal thoughts |
| Contrave (November 2025) | naltrexone/bupropion | weight | Boxed warning on suicidal thoughts and behaviors |
Source: the manufacturers' prescribing information on DailyMed, read 27 September 2026. The "Recent Major Changes" box of each GLP-1 label records the removal and its date.
The pattern in that table is the explanation. Semaglutide on the Ozempic label never had the warning; semaglutide on the Wegovy label did. Same molecule, different indication. The FDA's own account is that the warning sat on weight-management medicines as a class, "based on reports of such events observed with a variety of older medicines used or studied for weight loss" — not on a signal found with GLP-1 drugs. It stays on Qsymia, and Contrave's boxed warning comes from bupropion, an antidepressant. The other approved options are compared on GLP-1 alternatives.
What the FDA reviewed before removing it
The FDA began looking into postmarketing reports of suicidal thoughts in July 2023, said in January 2024 that its preliminary review had found no clear evidence of a link, and on 13 January 2026 asked for the warning to be removed. Its safety communication rests on two analyses:
| Analysis | Size | Result, in the FDA's words |
|---|---|---|
| Meta-analysis of placebo-controlled trials across the GLP-1 development programmes | 91 trials; 107,910 people (60,338 GLP-1, 47,572 placebo) | "did not show an increased risk for SI/B or for other relevant psychiatric adverse events such as anxiety, depression, irritability, or psychosis" |
| Sentinel observational study, October 2015 – September 2023 | 2,243,138 users (1,161,983 GLP-1; 1,081,155 on SGLT2 inhibitors) | "did not find an increased risk of intentional self-harm" in GLP-1 users compared with SGLT2 inhibitor users |
The comparison group in the second study matters: SGLT2 inhibitors are another class of diabetes drug, so both groups were people being treated for similar conditions — a fairer comparison than people on no treatment. The FDA's communication does not publish hazard ratios or confidence intervals for either analysis.
What did not change: the same communication still asks patients to tell their health care professional about "new or worsening depression, suicidal thoughts, or any unusual changes in mood or behavior." Removing a class warning is not the same as saying mood never needs watching.
Europe reached the same place earlier. In April 2024 the European Medicines Agency's safety committee (PRAC), after a review triggered by Iceland's medicines agency, with about 150 case reports under analysis, concluded that "the available evidence does not support a causal association" between GLP-1 drugs and suicidal or self-injurious thoughts, and that no change to product information was warranted. It reviewed postmarketing data, trials, the literature and two health-records studies, one of them its own.
The one trial analysis that measured depression directly
Most trials count psychiatric adverse events — what patients report. A 2024 post hoc analysis of the semaglutide STEP trials (Wadden et al., JAMA Internal Medicine) used two standard questionnaires, the PHQ-9 for depressive symptoms and the Columbia Suicide Severity Rating Scale, given throughout the trials:
| Measure (STEP 1, 2 and 3; 3,377 adults) | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| PHQ-9 at baseline (0–27 scale; under 5 = none or minimal) | 2.0 | 1.8 |
| PHQ-9 at week 68 | 2.0 | 2.4 |
| Moved to a more severe depression category | odds ratio 0.63 (0.50–0.79) vs placebo | — |
| Suicidal ideation or behavior during treatment | ≤1%, no difference | ≤1% |
The treatment difference was −0.56 PHQ-9 points in semaglutide's favour, which the authors describe as statistically significant but not clinically meaningful. STEP 5, a two-year trial, showed the same. Several authors are Novo Nordisk employees or received its funding, which the paper discloses.
What this evidence cannot tell you
The trials were run in people who were not depressed. The analysis above is titled as covering people "without known major psychopathology", and average baseline scores were in the no-or-minimal range. Tirzepatide's SURMOUNT-1 registry entry lists as exclusions a "history of significant active or unstable major depressive disorder … within the last 2 years" and "any lifetime history of a suicide attempt". So the reassuring numbers describe people screened for mental stability. For someone with current depression, the trial record is thin — which is a statement about what was studied, not a finding of risk.
The observational study compared drug with drug. It can say GLP-1 users did not self-harm more than SGLT2 users; it cannot say what would have happened to either group on nothing.
Reports still exist. Postmarketing reports of low mood and suicidal thoughts are what started both reviews. Both regulators judged that they did not add up to a causal signal; neither said such events never happen to someone taking these drugs. Weight change, stopping a drug and appetite loss all have their own effects on mood, and none of that is separated out in these analyses.
Could GLP-1 drugs treat depression?
Not shown. On 27 September 2026 ClinicalTrials.gov listed three semaglutide studies under the condition "depression" — a completed 72-person phase 2 trial on cognitive problems in major depressive disorder with no results posted, a 116-person phase 4 trial recruiting, and a lifestyle-intervention study not yet recruiting — and none for tirzepatide. The small improvement in STEP's PHQ-9 scores was in people who were barely symptomatic to begin with. Anything stronger than that is ahead of the evidence.
Where decisions sit
This page reports what the labels, regulators and trials say; it does not tell anyone whether to start, continue or stop a medicine. Mood changes on any treatment are for the prescriber, and anyone having thoughts of suicide in the US can call or text 988 at any hour. Stopping a GLP-1 has its own well-documented consequences, set out on stopping GLP-1 medication.
Sources
- FDA Drug Safety Communication, "FDA Requests Removal of Suicidal Behavior and Ideation Warning from Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) Medications", 13 January 2026.
- Prescribing information on DailyMed: Wegovy (effective 18 June 2026), Zepbound (28 August 2026), Saxenda (25 February 2026), Foundayo (29 July 2026), Qsymia (22 April 2026), Contrave (10 November 2025).
- European Medicines Agency, PRAC meeting highlights, 8–11 April 2024.
- Wadden TA et al. Psychiatric safety of semaglutide for weight management in people without known major psychopathology: post hoc analysis of the STEP 1, 2, 3, and 5 trials. JAMA Intern Med 2024;184(11):1290–1300. doi:10.1001/jamainternmed.2024.4346.
- ClinicalTrials.gov: NCT04184622 (SURMOUNT-1) eligibility criteria; condition search "depression" × semaglutide, tirzepatide, 27 September 2026.