GLP-1 and Mental Health: What's Documented About Mood and Anxiety

Matt Cole, host, Gila Podcast — edited by Sezen Soykut

This article covers research on GLP-1s and mental health, including suicidal thoughts. It is not medical advice. For questions about your own medication, talk to your prescriber. If you're having thoughts of suicide or self-harm, please reach out now: call or text 988 in the US (free, confidential, 24/7), or contact your local emergency number.

TL;DR: What research shows about GLP-1 medications and mood depends on which kind of data you look at. Two analyses of adverse-event reporting databases, by the same research team, found more reports than expected of suicidal thoughts (and, in one database, suicidal behavior) with semaglutide and liraglutide, but not of suicide attempts or suicide deaths. The EMA concluded that the available evidence "does not support a causal association" between the five GLP-1 medicines it reviewed and suicidal and self-injurious thoughts and actions. The FDA concluded that the totality of the studies it reviewed "does not support a causal relationship" with suicidal ideation and behavior, and in January 2026 asked for that warning to be removed from the three labels that carried it. Among people who already had depression or anxiety, a 2026 Swedish cohort study found that periods of semaglutide use were linked to less worsening of their condition, not more. Here's what each kind of evidence shows, what it can't show, and what you can do.

Key takeaways

1. Two analyses of adverse-event reporting databases, the FDA's FAERS and the WHO's VigiBase, both by the same research team, found more reports than expected of suicidal thoughts with semaglutide and liraglutide, and VigiBase found the same for suicidal behavior. Neither found more reports than expected of suicide attempts or suicide deaths, and VigiBase found significantly fewer. Data like this can't show cause in either direction.
2. Two regulators reviewed the question formally. The EMA concluded in April 2024 that "the available evidence does not support a causal association" between five GLP-1 medicines and suicidal and self-injurious thoughts and actions. After a meta-analysis of 91 placebo-controlled trials, the FDA concluded that the totality of the studies it reviewed "does not support a causal relationship," and in January 2026 asked for the suicidal behavior and ideation warning to be removed from the three labels that carried it.
3. In a 2026 Lancet Psychiatry study of more than 95,000 people in Sweden who already had depression or anxiety, periods of semaglutide use were linked to a 42% lower risk of their condition getting worse. It didn't study whether GLP-1s prevent depression or anxiety, and as an observational study it can't establish cause.
4. In a rat study, GLP-1 and a long-acting relative increased anxiety-like behavior when given short-term, while longer-term dosing reduced depression-like behavior. That's a possible biological explanation for mixed findings, not proof of what happens in people.
5. Three more studies found no sign of harm on the outcomes they measured: a 2025 JAMA Psychiatry review of randomized trials found no significant difference in serious psychiatric adverse events and no worsening of depressive symptoms, a small meta-analysis found a modest improvement in depression-scale scores, and a French national study linked recent GLP-1 use to lower, not higher, odds of suicide or suicide attempt.
6. If you're having thoughts of harming yourself, please reach out now rather than waiting for your next appointment: call or text 988 in the US, or contact your local crisis line or emergency number.

What adverse-event reports show, and what they can't

If you've noticed a shift in how you feel since starting a GLP-1, you deserve a straight answer about what's known. The straightest one is that it depends on which kind of data you look at, and it isn't the same for every outcome. That's less tidy than "it's all in your head" or "it's a known side effect," but it's closer to what the research shows. Start with adverse-event reporting databases, which collect voluntary reports of suspected side effects.

A 2024 analysis of the FDA's Adverse Event Reporting System (FAERS) looked at reports of suicidal ideation, "depression/suicidal," suicidal behavior, suicide attempts, and suicide deaths sent to the FDA between 2005 and October 2023. It found disproportionate reporting, meaning more reports than expected, of suicidal ideation and the combined category "depression/suicidal" with semaglutide and liraglutide. It did not find disproportionate reporting of suicidal behavior, suicide attempts, or suicide deaths for any FDA-approved GLP-1. Applying the Bradford Hill criteria for judging causation, and taking confounders into account, the authors concluded that no causal link between GLP-1s and suicidality could be established.

A 2025 follow-up by the same team, using the World Health Organization's global database VigiBase, found reporting odds significantly raised for suicidal ideation with semaglutide (5.82), liraglutide (4.03), and tirzepatide (2.25), and for "depression/suicidal" with semaglutide (14.74) and liraglutide (5.86). Unlike the FAERS analysis, it also found raised reporting odds for suicidal behavior with semaglutide (6.52) and liraglutide (3.90). But for suicide attempts and suicide deaths, reporting odds were significantly lower than expected for semaglutide, dulaglutide, exenatide, and liraglutide. The authors call this a "mixed pattern" and say causation, in either direction, can't be established from reporting-odds data.

A separate analysis of Europe's EudraVigilance database found 372 reports involving a psychiatric event for semaglutide, liraglutide, or tirzepatide between January 2021 and May 2023. Suicidal ideation appeared in 73 of them (19.6%). The analysis counted 102 suicide-related events in all, a figure that includes those 73 cases of ideation along with suicide attempts, suspected suicides, and four deaths by suicide. None of this is a rate: reports are voluntary, there's no count of how many people took the drug without a problem, and reports alone can't show that a drug caused anything.

Put together, both the FAERS and VigiBase analyses found more reports than expected of suicidal ideation with semaglutide and liraglutide, which is worth taking seriously. For suicide attempts and suicide deaths the picture was different: no increase in FAERS, and fewer reports than expected in VigiBase. Reports like these are a reason to investigate, not proof of cause, and the EMA's formal review, below, began after case reports of suicidal thoughts.

A possible mechanism, from animal research

GLP-1 is known for its effects on blood sugar and appetite, but the authors of a 2016 rat study note that it may also affect brain areas involved in regulating emotion. In that study, GLP-1 and its long-acting relative exendin-4 increased anxiety-like behavior in three rodent tests when given acutely, and acute stimulation of GLP-1 receptors in the brain changed serotonin signaling in the amygdala. Longer-term dosing told a different story: chronic exendin-4 delivered into the brain didn't increase anxiety-like behavior, and it significantly reduced depression-like behavior. Rats fed the same reduced amount of food without the drug showed no change in mood-related behavior, so the effect wasn't simply a result of eating less.

This is rat data, and much of the dosing went directly into the brain, so it can't be assumed to translate to people taking these medicines. What it offers is biological plausibility: a reason short-term and longer-term effects on emotion could differ. It isn't evidence of what happens in people.

What the regulators reviewed — and concluded

Two regulators ran formal safety reviews focused on GLP-1s and suicidal thoughts or self-harm. It's worth being precise about what each one examined and what each one said.

The European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) started its review in July 2023, after case reports of suicidal thoughts and thoughts of self-injury from people using liraglutide and semaglutide. It looked at non-clinical studies, clinical trials, post-marketing surveillance data, and other available studies. In April 2024, it concluded that "the available evidence does not support a causal association" between five GLP-1 medicines (dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide, sold as Ozempic, Rybelsus, Wegovy, Victoza, Saxenda, and Trulicity, among others) and suicidal and self-injurious thoughts and actions. It considered that no update to the product information was warranted, and the companies that market these medicines will keep monitoring for new evidence.

The FDA reviewed the question in two steps. Its initial review of GLP-1 clinical-trial data, shared in January 2024, did not find an association with suicidal thoughts or behavior, but because there were so few cases in individual trials, the FDA said there was "considerable uncertainty in the risk estimate." It then ran a meta-analysis of 91 placebo-controlled trials covering 107,910 patients (60,338 on a GLP-1, 47,572 on placebo). The results did not show an increased risk of suicidal thoughts or behavior, or of other psychiatric adverse events such as anxiety, depression, irritability, or psychosis. On January 13, 2026, the FDA said its review concluded that the totality of these studies "does not support a causal relationship," and asked manufacturers to remove information about the risk of suicidal ideation and behavior from the labels of Saxenda (liraglutide), Wegovy (semaglutide), and Zepbound (tirzepatide), the GLP-1 medicines whose labels included it.

Those are meaningful, reassuring findings about suicidal thoughts and behavior across large groups of people. They can't tell you how you, individually, will feel, which is why your own experience still counts.

A 2025 systematic review and meta-analysis in JAMA Psychiatry, pooling 80 randomized controlled trials and 107,860 participants, points the same way on the questions it could answer. It found no significant difference in serious psychiatric adverse events between GLP-1s and placebo, and no evidence of an association between GLP-1 treatment and a change in depressive symptoms. Its limits matter too: for anxiety and for suicidality it found only three studies each, too few to pool, so its 107,860-participant total can't support any conclusion about anxiety or suicidality.

The other side: studies that found less worsening, not more

Set against the mixed reporting-database picture above, studies that compare people on GLP-1s with a control group, or with themselves at other times, point toward less worsening rather than more.

A 2026 study in The Lancet Psychiatry, by researchers at the Karolinska Institutet, the University of Eastern Finland, and Griffith University, followed 95,490 people in Swedish national registers who already had a diagnosis of depression or an anxiety disorder and used diabetes medication, between 2009 and 2022. It compared periods when the same individuals were and weren't using a GLP-1. During semaglutide-use periods, the risk of their mental illness getting worse (psychiatric hospitalization, more than 14 days of psychiatric sick leave, hospitalization for self-harm, or suicide death) was 42% lower than during non-use periods (adjusted hazard ratio, or aHR, 0.58; 95% confidence interval 0.51–0.65). Liraglutide use was linked to an 18% lower risk (aHR 0.82; 95% CI 0.76–0.89). Exenatide and dulaglutide were not associated with a lower risk (exenatide aHR 1.01, 95% CI 0.69–1.46; dulaglutide aHR 1.01, 95% CI 0.85–1.20). For self-harm specifically, the study reports a result for GLP-1 medicines as a group, not for semaglutide alone: a lower risk (aHR 0.56), with a wide confidence interval (0.34–0.92), so the true size of that difference is uncertain.

The key detail: this study didn't ask whether GLP-1s cause or prevent depression or anxiety in the general population. It asked whether people who already had depression or anxiety, and were taking diabetes medication, were less likely to get worse during periods on a GLP-1. It's observational, so it can't prove the medication caused the difference. For a closer look, see GLP-1s and Existing Depression or Anxiety: What the Swedish Study Actually Found.

Separately, a 2024 French nationwide study used national health-insurance data to look at 1,102 people who died by suicide or were hospitalized after a suicide attempt, comparing their GLP-1 use in the month before the event with earlier periods in their own history. GLP-1 use was linked to significantly lower odds of suicide or suicide attempt (odds ratio 0.62; 95% CI 0.51–0.75), and results were similar for people with a recent psychiatric history. A design like this can't show that the drug protects against suicide. It only shows that, among people who did attempt or die by suicide, recent GLP-1 use was less common than expected. Still, the direction is lower, not higher.

And a small meta-analysis of five randomized trials and one cohort study (2,071 people in total) found a statistically significant but small improvement in depression-rating-scale scores with GLP-1 treatment compared with control (standardized mean difference −0.12). That's a real but small effect, not evidence that GLP-1s work as an antidepressant.

How do you hold this next to the reporting-database picture above? Both can be true, because they aren't measuring the same thing. The studies in this section estimate risk or symptom change against a comparison, in a defined group of people, over a defined period. Reporting databases collect voluntary reports with no count of how many people took the drug without a problem. More reports than expected in a database and a lower-risk association in a controlled study aren't a contradiction. They're two instruments answering two different questions, and an honest reading holds both.

Irritability, motivation, and flatness, specifically

Three more specific questions are worth taking one at a time.

Irritability. The FDA's analysis of 91 placebo-controlled trials did not show an increased risk of irritability compared with placebo. That's an average across trials, so if you've become noticeably short-tempered since starting treatment, it's still worth mentioning to your prescriber.

Reduced motivation. We couldn't find a verified study showing that GLP-1s reduce motivation, so we won't claim that they do. If your drive or enjoyment has changed since you started treatment, it's still worth raising with your prescriber. For the related question of whether these medicines change personality, see Do GLP-1s Change Your Personality?

Emotional flatness or low mood. We couldn't find verified evidence on emotional flatness specifically. The closest evidence is on depression: trial data show no worsening of depressive symptoms on average, while the reporting databases show more reports than expected of the combined "depression/suicidal" category with semaglutide and liraglutide, which can't show that the drug caused any individual case. If flatness or low mood has set in since you started treatment, raise it with your prescriber rather than assuming it's unrelated to the medication, or assuming it must be.

What you can do

Whatever is or isn't happening for you, a few practical steps can help you see it clearly and talk about it.

Name what you feel, specifically. "I feel off" is hard to act on. "I feel anxious in the evenings, before dinner" is something you can compare with your dosing schedule, sleep, and meals.

Track mood alongside doses, sleep, and meals, not just weight. Patterns that feel random in the moment, like a rough Tuesday or a hard week, are clearer when they're laid out together. Gila lets you log mood alongside your doses, food, and habits, so you can bring your prescriber a few weeks of notes instead of a reconstruction from memory. If you'd like somewhere to start, the habit readiness assessment is a low-pressure first step.

Plan for the harder moments. Decide in advance on a few small things you can reach for, like a short walk, a text to a friend, or five minutes of a hobby you've set aside.

Don't tough out a bad stretch alone. A low mood or new anxiety that's making your days harder is information for your care team, not something to push through on your own.

When to call your prescriber

A few changes are worth a call rather than a wait-and-see:

• Low mood, anxiety, or irritability that isn't lifting, or is getting worse
• A noticeable loss of interest in things you normally enjoy
• Mood changes that began around the time you started treatment or had a dose change (note when they began, so you can tell your prescriber)
• Any thoughts of self-harm, even passing ones, even if you don't think you'd act on them

That last one deserves its own sentence, said plainly: if you're having thoughts of harming yourself, please reach out now. Tell your prescriber, call or text 988 in the US (free, confidential, 24/7), call your local emergency number, or go to an emergency room. You don't have to decide alone whether it's "serious enough" to mention.

Telling your prescriber how you feel isn't a sign you've failed at the medication or at managing your mood. It's how they can support you: the system working as intended, not a last resort.

Frequently asked questions

Can GLP-1s cause anxiety? The trial evidence doesn't show it on average: the FDA's analysis of 91 placebo-controlled trials did not show an increased risk of anxiety as an adverse event compared with placebo. Studies measuring anxiety as an outcome are scarcer: a 2025 JAMA Psychiatry review found only three, too few to pool. In a rat study, GLP-1 and a long-acting relative increased anxiety-like behavior when given short-term but not with longer-term dosing, which can't be assumed to apply to people. And in one analysis of Europe's EudraVigilance database, anxiety was the most commonly reported psychiatric event after depression, though reports like these can't show cause or how common it is. If you notice new or worsening anxiety, raise it with your prescriber.

Can GLP-1 make you depressed? On average, the trial evidence doesn't show that. A 2025 JAMA Psychiatry review of randomized trials found no evidence of an association between GLP-1 treatment and a change in depressive symptoms, and a smaller meta-analysis found a modest improvement in depression-rating-scale scores. Reporting databases do show more reports than expected of a combined "depression/suicidal" category with semaglutide and liraglutide, a signal worth taking seriously but not proof that the drug caused any individual case. If your mood has changed since you started treatment, raise it with your prescriber, whatever the averages show.

What are the psychological side effects of GLP-1s? What gets reported and what a medication has been shown to cause are different things. In one analysis of Europe's EudraVigilance database, 372 reports for semaglutide, liraglutide, or tirzepatide between January 2021 and May 2023 involved a psychiatric event; depression was reported most often, followed by anxiety and suicidal ideation (73 reports, or 19.6%). But in the FDA's analysis of 91 placebo-controlled trials, the results did not show an increased risk of suicidal thoughts or behavior, anxiety, depression, irritability, or psychosis compared with placebo. Reports reflect what people chose to send in, not what will happen to you, and there's no count of how many people took the drug without a problem.

Do GLP-1s cause irritability? The FDA's analysis of 91 placebo-controlled trials did not show an increased risk of irritability compared with placebo. That's an average, so if you've become noticeably short-tempered since starting treatment, it's still worth mentioning to your prescriber.

Do GLP-1s reduce motivation? We couldn't find a verified study showing that GLP-1s reduce motivation, so we can't say that they do. If your drive or enjoyment has changed since you started treatment, it's still worth raising with your prescriber.

Did the FDA or EMA find that GLP-1s cause suicidal thoughts? No. The EMA concluded in April 2024 that "the available evidence does not support a causal association" between five GLP-1 medicines and suicidal and self-injurious thoughts and actions. The FDA said in January 2026 that the totality of the studies it reviewed "does not support a causal relationship," and asked manufacturers to remove information about the risk of suicidal ideation and behavior from the labels of Saxenda, Wegovy, and Zepbound. Evidence that doesn't support a causal link isn't the same as proof of no risk, and in the EU the companies that market these medicines will keep monitoring for new evidence. If you're having thoughts of suicide or self-harm, please reach out now: call or text 988 in the US, or call your local emergency number.

Can GLP-1s affect anxiety, ADHD, and other conditions? The evidence in this article covers depression, anxiety, and suicidality. We couldn't find rigorous, peer-reviewed evidence linking GLP-1s to ADHD symptoms, so we won't claim a link. If you take ADHD medication alongside a GLP-1, make sure each of your prescribers knows about both.

Methodology: how we sourced this

Every clinical claim above links to a peer-reviewed study, an FDA or EMA regulatory communication, or a published analysis of a pharmacovigilance database, never a news summary. Where reporting-database signals and controlled-study findings seemed to disagree, we described both and explained why both can be accurate. Where we couldn't verify a claim against a primary source, including the questions on motivation and ADHD, we said so instead of repeating a plausible-sounding line.

Matt Cole is a host of the Gila Podcast. Articles under his name are written by the Gila editorial team and edited by Sezen Soykut, Gila's founder and editor-in-chief. Full source list below.

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Sources

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