Mental Health and Weight-Loss Injections: What Does the Science Reveal?

Do semaglutide and tirzepatide increase the risk of depression, anxiety, or suicidal thoughts?

Medications popularly known as “weight-loss injections” have transformed the treatment of obesity. Semaglutide, liraglutide, and, more recently, tirzepatide have made it possible to achieve levels of weight loss that were previously difficult to attain through lifestyle changes alone.

At the same time, as millions of people began using these medications, an important concern emerged: could GLP-1 receptor agonists increase the risk of depression, anxiety, mood changes, or even suicidal thoughts?

This question became sufficiently important that regulatory agencies began specifically investigating the psychiatric safety of these medications.

Recent studies are now helping us better understand this relationship.

Obesity and Mental Health: A Two-Way Relationship

Before discussing the medications themselves, it is important to remember that obesity is closely linked to mental health.

People living with obesity have higher rates of depression, anxiety, and impaired quality of life. Conversely, psychiatric disorders may also contribute to weight gain through several mechanisms, including changes in appetite, reduced physical activity, and the effects of certain medications.

In addition to biological mechanisms, another important factor must be considered: weight stigma. Prejudice, discrimination, low self-esteem, and social isolation can significantly affect psychological well-being.

Mental health should therefore be considered an integral part of comprehensive obesity care.

This also makes it difficult to answer an apparently simple question: when a person undergoing obesity treatment develops depression or anxiety, what is the contribution of the underlying disease, psychosocial circumstances, weight loss itself, and the medication?

The Initial Safety Signal

In 2024, a study published in the International Journal of Clinical Pharmacy analyzed adverse-event reports involving semaglutide, liraglutide, and tirzepatide submitted to the European EudraVigilance database between January 2021 and May 2023.

The researchers identified 31,444 adverse-event reports. Of these, 372 involved psychiatric adverse events, representing approximately 1.18% of all reports. Among these psychiatric reports, depression, anxiety, and suicidal ideation were the most frequently reported events.

These findings attracted attention and justified further investigation.

However, there is a fundamental difference between identifying a pharmacovigilance safety signal and demonstrating that a medication actually causes an adverse event.

Spontaneous-reporting databases are extremely valuable for identifying potential safety concerns, but they cannot, on their own, establish a causal relationship.

Larger studies using different research methodologies were therefore needed.

What Did a 2026 Study Find?

A study published in Communications Medicine in 2026 analyzed U.S. electronic health record data from 2020 to 2025.

The researchers evaluated adults with obesity who initiated semaglutide or tirzepatide and compared their neuropsychiatric outcomes with those of patients who initiated other prescription weight-loss medications. Participants were followed for up to 24 months.

The results were particularly interesting.

Compared with naltrexone-bupropion, semaglutide was associated with lower hazards of anxiety and depression, both among people with type 2 diabetes and among those without diabetes.

Tirzepatide showed a similar pattern, with lower hazards of anxiety and depression in several comparisons with naltrexone-bupropion.

This does not mean that semaglutide or tirzepatide should be considered treatments for depression or anxiety. This was an observational study, and therefore it demonstrates associations rather than causation.

There was also an important nuance. Among individuals with obesity without type 2 diabetes, the direct comparison between the two medications showed that tirzepatide was associated with modestly higher hazards of anxiety and insomnia than semaglutide. The authors themselves emphasize that these findings require confirmation.

The scientific message, therefore, is not simply that these medications are either “good” or “bad” for mental health. The findings vary according to the medication, the comparator, and the clinical characteristics of the patients.

What About the Risk of Suicide?

This is where an important shift in the evidence has occurred.

In January 2026, the U.S. Food and Drug Administration (FDA) announced that its comprehensive evaluation did not identify an increased risk of suicidal ideation or behavior associated with GLP-1 receptor agonists.

As a result, the agency requested the removal of this warning from the prescribing information for medications that still included it, specifically Saxenda (liraglutide), Wegovy (semaglutide), and Zepbound (tirzepatide).

The scale of this evaluation is particularly noteworthy.

The FDA conducted a meta-analysis of 91 placebo-controlled clinical trials involving 107,910 participants—60,338 treated with GLP-1 receptor agonists and 47,572 receiving placebo.

The analysis found no increased risk of suicidal ideation or behavior and no increased risk of other relevant psychiatric adverse events, including anxiety, depression, irritability, or psychosis.

The FDA also analyzed data from its Sentinel System involving more than 2.2 million individuals. It found no increased risk of intentional self-harm among users of GLP-1 receptor agonists compared with users of SGLT2 inhibitors.

After considering clinical trials, observational studies, and other available evidence, the FDA concluded that the totality of the evidence does not support a causal relationship between GLP-1 receptor agonists and suicidal ideation or behavior.

Does This Mean Weight-Loss Injections Have No Effect on Mental Health?

That would be an overly broad interpretation of the current evidence.

A more appropriate conclusion is that, based on the best evidence currently available, GLP-1 receptor agonists have not been shown to increase the risk of suicidal ideation or behavior.

This is different from saying that no individual patient can experience mood changes while undergoing treatment.

Every patient has an individual clinical history, psychological vulnerabilities, and potentially pre-existing psychiatric conditions. In addition, the process of losing a substantial amount of weight can involve important physical, behavioral, social, and emotional changes.

For this reason, new or worsening depression, significant mood changes, suicidal thoughts, or unusual behavioral changes should always be reported to a healthcare professional and appropriately evaluated. The FDA continues to recommend medical evaluation of these symptoms despite requesting removal of the specific suicidal ideation warning.

Obesity Treatment Goes Far Beyond the Number on the Scale

Perhaps this is the most important message.

Obesity is a chronic, complex, and multifactorial disease. The success of treatment should not be measured exclusively by the number of kilograms or pounds lost.

Comprehensive obesity care should also consider metabolic health, body composition, nutritional status, physical function, eating behavior, quality of life, and mental health.

Semaglutide, tirzepatide, and other modern anti-obesity medications represent a major advance in obesity treatment. However, medication does not replace appropriate medical and nutritional follow-up or, when indicated, psychological or psychiatric care.

Science also evolves. A potential safety signal identified through pharmacovigilance must be investigated—and that is precisely what occurred in this case. Subsequent studies involving much larger populations and different methodologies have provided more robust and reassuring information.

Current evidence does not support the conclusion that GLP-1 receptor agonists increase the risk of suicide. Some observational studies have even found lower rates of certain anxiety and depression diagnoses in specific comparisons, but these findings are not sufficient to conclude that these medications have a protective effect on mental health.

Ultimately, the goal is to treat the person—not simply their weight.

Weight loss is one component of treatment. Improving overall health—both physical and mental—is the real goal.

Main References

Tobaiqy M, Elkout H. Psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide: a pharmacovigilance analysis of individual case safety reports submitted to the EudraVigilance database. International Journal of Clinical Pharmacy. 2024;46:488–495.

Huang YN, Liu KW, Li PH, et al. Neuropsychiatric association of tirzepatide and semaglutide in obesity with and without type 2 diabetes. Communications Medicine. 2026.

U.S. Food and Drug Administration. FDA Requests Removal of Suicidal Behavior and Ideation Warning from Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) Medications. January 2026.