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Some people feel flat, anxious, or low in the first weeks on semaglutide or tirzepatide. The FDA’s latest review, from January 2026, found no sign that the drugs raise the risk of suicidal thoughts, depression, or anxiety. When your mood drops, there can be many causes, like eating much less, sleeping badly, losing a way of coping, or depression that was there before. Your clinician can help sort out which ones apply to you. If you’re having thoughts of suicide right now, call or text 988 (the 988 Suicide & Crisis Lifeline) or text HOME to 741741 (Crisis Text Line). Both are free and open 24 hours a day.
What the FDA found
In 2023, reports of suicidal thoughts in people on GLP-1s led to safety reviews in the US and Europe. In January 2024 the FDA’s preliminary review found no evidence that the drugs caused suicidal thoughts or actions, but said it couldn’t rule out a small risk. In April 2024 the EMA’s safety committee (PRAC) concluded that the evidence did not support a causal link.
The FDA’s full review came out on January 13, 2026. It covered two main sources:
- 91 placebo-controlled trials with 107,910 patients (60,338 on a GLP-1, 47,572 on placebo). People on the drugs had no more suicidal thoughts or behavior than people on placebo, and no more anxiety, depression, irritability, or psychosis.
- A Sentinel cohort of 2,243,138 people who started either a GLP-1 or an SGLT2 inhibitor, another diabetes drug class. Rates of intentional self-harm were compared between the two groups.
The FDA then asked the makers to remove the suicidal behavior warning from the Saxenda, Wegovy, and Zepbound labels. The current Wegovy and Zepbound labels list that section as removed as of February 2026.
What the evidence can’t tell you yet
The trials behind that review mostly left out the people most at risk. STEP 1, the main weight-loss trial of brand-name semaglutide (Wegovy), excluded anyone with major depression in the past two years, a PHQ-9 depression score of 15 or higher, or any past suicide attempt. So we know much less about how these drugs affect people with serious depression or a history of suicide attempts. That is why your prescriber needs your history (see below).
Why mood can dip early
Several of these often happen at once.
- A sudden drop in how much you eat. Appetite can fall sharply within days, and eating far less than usual can leave you irritable, foggy, and low.
- Too little protein. When meals shrink, protein is usually what disappears first. The food guide covers how to protect it.
- Dehydration. Less food means less water, and nausea makes drinking harder.
- Low blood sugar. Anxiety, irritability, and mood changes are on the labels’ list of low blood sugar symptoms. The risk is mainly for people also taking insulin or a sulfonylurea.
- Poor sleep. Reflux and nausea at night break up sleep, which makes everything else worse.
- Fatigue. The side effects guide covers how often it shows up and how long it lasts.
- Losing food as a way to cope. If eating was how you handled stress, the medication can take that away before anything replaces it. The food noise article covers what goes quiet, and emotional eating covers what’s often underneath it.
- Adjusting to a changing body. Your body, and how people react to it, can change faster than your sense of yourself. That can be unsettling even when you wanted the change.
Some dips ease once your eating settles, and some don’t. A low mood that lasts may be depression that started before the medication. No one can promise it will pass, so if it lasts more than two weeks, tell your clinician.
What helps
- Eat enough, and eat protein first. Ask your clinician how much protein is right for you. The protein calculator can give you a starting point.
- Drink before you’re thirsty, and drink more on days with nausea or diarrhea.
- Protect your sleep. If reflux keeps you up, stop eating a few hours before bed.
- Watch caffeine. With a small breakfast, your usual coffee can hit harder. Cut back if you feel jittery or anxious.
- Move most days. A walk counts. Resistance training twice a week also protects muscle.
- Talk to someone. A friend, a therapist, or your clinician. Saying it out loud helps you notice how long it has been going on.
If nausea is stopping you from eating, your clinician may slow your dose increases or pause at your current dose. Ask before you change your dose yourself.
When to get help the same day
Taking the warning off the label doesn’t make these symptoms less urgent. Get help today if you have:
- Depression that is getting worse, or new hopelessness
- Thoughts of suicide or of harming yourself
- Changes in mood or behavior that you or people close to you notice
Call or text 988, or text HOME to 741741. If you’re in immediate danger, call 911. Then tell your prescriber.
If you’re on a compounded version
Compounded semaglutide and tirzepatide aren’t FDA-approved and have no FDA label of their own. They have no trials of their own. The trial findings were measured on the brand-name products.
Tell your prescriber your mental health history
Before you start, tell your prescriber about any antidepressant or other psychiatric medication. Also mention any history of depression, suicide attempts, bipolar disorder, or an eating disorder.
The first reason is fit. Those are the groups the trials left out, and a past eating disorder changes how appetite suppression should be handled.
The second is drug interactions. Both labels say the slower gastric emptying can change how well oral medications are absorbed, and they advise closer monitoring for drugs with a narrow therapeutic range. Lithium is one of those drugs. Vomiting or diarrhea can also dehydrate you, which raises lithium levels. Keep taking your psychiatric medication as prescribed, and don’t stop or change it because you started a GLP-1.
Starting through Zappy? Put all of this in the intake. Already on a GLP-1 and your mood has changed? Message your clinician this week, and tell them how much you’ve been eating, drinking, and sleeping. The safety information lists the full warnings.
