Zepbound® and mood changes

If you need help now

Thoughts of suicide, of harming yourself or of not wanting to be alive need help today, not at the next appointment. In the US, call or text 988 or use 988lifeline.org, which offers free support 24 hours a day; ^[5][10] anywhere, you can call your local emergency number or go to the nearest emergency department. ^[9] If someone you know has attempted suicide, call emergency services right away and do not leave them alone. ^[9]

How the official documents changed

Zepbound® was approved for weight reduction with a warning about suicidal behaviour and ideation, the same language used for other weight-loss medicines. The FDA later asked the makers of Saxenda®, Wegovy® and Zepbound® to remove it. ^[5] Its review combined a meta-analysis of 91 placebo-controlled GLP-1 trials with 107,910 participants, a study of more than 2.2 million people in US claims data, and published observational research, and concluded that the evidence did not support a causal link. ^[5] The current Zepbound® label records the warning as removed in February 2026, ^[1] and the August 2026 Medication Guide has no depression section. ^[2]

Other regulators have not all made the same change. The table below shows where things stand.

What the Zepbound® trials and later studies show

The closest data to Zepbound® come from a 2026 post hoc analysis of SURMOUNT-1, -2 and -3, covering 4,056 adults with obesity and no known major psychiatric illness. Depression symptoms were measured with a standard questionnaire (PHQ-9) and suicidal thoughts with a structured scale. Average depression scores started low and fell slightly more on tirzepatide (from 2.7 to 1.9) than on placebo (2.6 to 2.4), and fewer people on tirzepatide moved to a more severe category (18.2% vs 24.3%). Suicidal ideation was reported by 0.6% in each group, and non-fatal suicidal behaviour by 0.1% on tirzepatide and none on placebo. ^[6] The authors say people with significant psychiatric illness need further study.

Large record studies add context but cannot prove cause. In one, covering about 85,000 matched pairs, tirzepatide and semaglutide had similar rates of a combined outcome of depression, anxiety and suicidal ideation over two years, with a nominally higher anxiety rate for tirzepatide in the second year that the authors advise reading cautiously. ^[7] In another, tirzepatide users had lower rates of anxiety and depression diagnoses than people starting naltrexone-bupropion, but in adults without diabetes slightly higher anxiety and insomnia than semaglutide users. ^[8]

Things on treatment that can affect mood

None of these is listed as a Zepbound® side effect, but each is described in its documents or in public health sources.

• Low blood sugar. Anxiety, irritability and mood changes appear among warning signs in the Medication Guide. ^[2] The risk is mainly in people with type 2 diabetes, highest with a sulfonylurea or insulin. ^[1]
• Eating very little. The Canadian patient information lists malnutrition, with irritability, weakness and trouble paying attention, among side effects that need a clinician. ^[3]
• Poor sleep and sleep apnea. MedlinePlus notes that people with sleep apnea may be irritable or impatient and lists depression among related problems. ^[11] Sleeping problems are also a recognised trigger of depression. ^[9]
• Feeling unwell. Persistent nausea, vomiting or fatigue in the first weeks can wear anyone down; fatigue was reported by 5–7% on Zepbound® versus 3% on placebo. ^[1]

Causes outside the injection

MedlinePlus lists stressful life events, social isolation, alcohol or drug use, chronic pain, an underactive thyroid and some medicines, such as steroids and beta-blockers, among factors that can bring on depression; depression also runs in families. ^[9] Its symptoms include irritability, loss of interest in things once enjoyed, hopelessness, trouble concentrating, changes in sleep and appetite, and thoughts of death. ^[9]

Several of these overlap with what changes when someone starts a weight treatment, including appetite, sleep and energy, which is one reason to describe mood symptoms in detail rather than assume the medicine is or is not responsible.

What to do and who decides

The FDA asks patients to keep taking GLP-1 medicines as prescribed, to discuss concerns with their clinician, and to report new or worsening depression, suicidal thoughts or unusual changes in mood or behaviour. ^[5] The Canadian patient information asks you to pay attention to changes in mood, behaviour, feelings or thoughts and to call your clinician right away about thoughts of self-harm or mental health changes that are new, worse or worrying. ^[3] Family members often notice these changes first.

MedlinePlus advises contacting a provider if low mood affects work or family life for more than two weeks, if you have three or more symptoms of depression, or if you think a medicine is making you feel depressed, and not to stop any medicine without talking to your provider first. ^[9] Whether Zepbound® continues is a decision for you and your prescriber together.

Zepbound® and Mounjaro® are registered trademarks of Eli Lilly and Company. Saxenda® and Wegovy® are registered trademarks of Novo Nordisk A/S. PepLabo is not affiliated with or endorsed by Eli Lilly and Company or Novo Nordisk.

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