Does Mounjaro Make You Depressed? UK Clinical Evidence

Mounjaro (tirzepatide) is a dual GIP and GLP-1 receptor agonist licensed in the UK for type 2 diabetes and weight management. As with any medication causing significant metabolic changes, patients have raised concerns about potential effects on mental health, particularly depression. Current evidence does not establish a causal link between Mounjaro and depression. The European Medicines Agency's Pharmacovigilance Risk Assessment Committee concluded in 2024 that available data do not support an association between GLP-1 receptor agonists and suicidal thoughts or self-harm. However, understanding mood changes during treatment remains important for patient safety and wellbeing.

Understanding Mounjaro and Mental Health Concerns

Mounjaro (tirzepatide) is a relatively new medication licensed in the UK for the treatment of type 2 diabetes mellitus. Tirzepatide is also authorised for weight management in adults with obesity or overweight with weight-related comorbidities, though in the UK this may be marketed under a different brand name. As a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, Mounjaro works by mimicking naturally occurring incretin hormones that regulate blood glucose levels, slow gastric emptying, and reduce appetite.

As with any medication that affects metabolic processes and leads to significant weight loss, patients and healthcare professionals have raised questions about potential effects on mental health, particularly depression. These concerns are understandable given that:

• Weight loss itself can be associated with psychological changes

• Lifestyle modifications accompanying treatment can be emotionally challenging

• Some patients may have pre-existing mental health vulnerabilities

• Chronic conditions like diabetes and obesity have higher baseline rates of depression

It is important to note that there is currently no established causal link between Mounjaro and depression in the clinical literature. This is supported by the European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC), which concluded in 2024 that available evidence does not support a causal association between GLP-1 receptor agonists and suicidal thoughts or self-harm. However, the Medicines and Healthcare products Regulatory Agency (MHRA) and EMA continue to monitor post-marketing safety data for all GLP-1 receptor agonists and related medications.

Understanding the distinction between correlation and causation is essential. Patients taking Mounjaro may experience mood changes for various reasons unrelated to the medication itself, including the psychological impact of chronic disease management, body image concerns, or coincidental life stressors.

Clinical Evidence on Mounjaro and Depression

The clinical trial programme for tirzepatide, including the SURPASS trials for diabetes and SURMOUNT trials for weight management, did not identify depression as a common or significant adverse effect. In these large-scale, randomised controlled trials involving thousands of participants, mood disorders were not reported at rates substantially different from placebo groups.

Key findings from the evidence base include:

• Depression is not listed among the common adverse effects (occurring in ≥1/100 patients) in the UK Summary of Product Characteristics (SmPC) for Mounjaro

• Psychiatric adverse events were monitored but did not emerge as safety signals during phase 3 trials

• The most frequently reported side effects remain gastrointestinal (nausea, diarrhoea, vomiting, constipation)

• No mechanistic pathway has been established linking GIP/GLP-1 receptor agonism directly to depressive symptoms

However, post-marketing surveillance continues to be crucial. Real-world use involves more diverse patient populations than clinical trials, including individuals with complex medical histories, polypharmacy, and pre-existing mental health conditions. The MHRA's Yellow Card scheme collects reports of suspected adverse drug reactions. Patients and healthcare professionals should report any suspected side effects to the Yellow Card Scheme at yellowcard.mhra.gov.uk or via the Yellow Card app.

Some preliminary research has explored whether GLP-1 receptor agonists might have potential neuroprotective properties, given the presence of GLP-1 receptors in brain regions involved in mood regulation. However, this remains largely exploratory and preclinical, with no established clinical benefit for mood disorders.

Patients should be reassured that current evidence does not support a direct causal relationship between Mounjaro and depression, though individual experiences may vary and warrant clinical attention.

Recognising Depression Symptoms While Taking Mounjaro

Whether or not depression is causally related to Mounjaro, it is essential that patients and healthcare professionals can recognise depressive symptoms promptly. Depression is a common condition affecting approximately 1 in 6 adults in the UK in any given week, according to NHS data, and people with chronic conditions like type 2 diabetes or obesity have higher baseline rates of depression.

Core symptoms of depression include:

• Persistent low mood or sadness lasting most of the day, nearly every day, for at least two weeks

• Loss of interest or pleasure (anhedonia) in activities previously enjoyed

• Fatigue or loss of energy, even with adequate rest

• Changes in appetite or weight (beyond expected Mounjaro-related weight loss)

• Sleep disturbances (insomnia or hypersomnia)

• Difficulty concentrating or making decisions

• Feelings of worthlessness or excessive guilt

• Recurrent thoughts of death or suicidal ideation

It can be challenging to distinguish between medication side effects and depression. For example, nausea and reduced appetite are expected with Mounjaro, but when accompanied by profound sadness, hopelessness, or social withdrawal, they may indicate depression. Similarly, fatigue might result from caloric restriction during weight loss or represent a depressive symptom.

Important differentiating features:

• Depression typically involves pervasive mood changes affecting multiple life domains

• Physical side effects of Mounjaro usually improve after the first few weeks of treatment

• Depression often includes cognitive symptoms (negative thinking patterns, poor concentration) beyond physical complaints

Patients should maintain open communication with their healthcare team about any mood changes, particularly if symptoms persist beyond the initial adjustment period or significantly impair daily functioning.

Risk Factors and Who May Be More Vulnerable

Certain patient groups may be at higher baseline risk for developing depression, whether or not they are taking Mounjaro. Identifying these vulnerabilities allows for more vigilant monitoring and earlier intervention if mood disturbances emerge.

Pre-existing mental health conditions:

Patients with a personal or family history of depression, anxiety disorders, bipolar disorder, or other psychiatric conditions require careful assessment before starting Mounjaro. While there is no absolute contraindication, these individuals may benefit from closer mental health monitoring and coordination between their GP, diabetes specialist, and mental health services. Patients and carers should be advised to seek medical advice promptly if new or worsening mood changes occur.

Chronic disease burden:

Living with type 2 diabetes or obesity itself increases depression risk. The psychological impact of managing a chronic condition, concerns about complications, and societal stigma surrounding weight can all contribute to mood disturbances. The relationship is bidirectional—depression can also worsen glycaemic control and weight management outcomes.

Significant life stressors:

Patients experiencing major life changes, bereavement, relationship difficulties, financial stress, or social isolation may be more vulnerable to depression. Starting a new medication during such periods requires additional support.

Rapid weight loss:

Whilst generally beneficial, rapid weight loss can occasionally be associated with psychological challenges, including body image concerns. Some patients may develop disordered eating patterns or struggle with changing body size or altered social dynamics. Healthcare professionals should remain vigilant for signs of disordered eating behaviours.

Medication considerations:

A comprehensive medication review is advisable when starting Mounjaro, as some medications may influence mood and multiple drug interactions are possible.

NICE guidance on depression in adults (NG222, which supersedes the earlier CG91) emphasises the importance of screening for depression in patients with chronic physical health conditions like diabetes, using validated tools such as the Patient Health Questionnaire-9 (PHQ-9) when appropriate.

What to Do If You Experience Mood Changes on Mounjaro

If you notice mood changes, low mood, or symptoms of depression whilst taking Mounjaro, it is important to take these seriously and seek appropriate support. Do not stop taking Mounjaro without speaking to your healthcare professional, as this may affect your diabetes control or weight management progress.

Immediate steps to take:

• Contact your GP or diabetes specialist nurse to discuss your symptoms. Be specific about when symptoms started, their severity, and how they affect your daily life

• Keep a symptom diary noting mood patterns, potential triggers, sleep quality, and any physical symptoms

• If you experience thoughts of self-harm or suicide, seek urgent help by contacting your GP for an emergency appointment, calling NHS 111, calling 999 or attending A&E if you are in immediate danger. The Samaritans (116 123) provide 24/7 confidential support

Your healthcare professional may:

• Conduct a thorough assessment using validated depression screening tools

• Review all your medications to identify potential interactions or contributors

• Consider whether symptoms might be related to Mounjaro, the underlying condition, or other factors

• Discuss whether continuing, adjusting, or temporarily pausing Mounjaro is appropriate

• Arrange blood tests to exclude other causes (thyroid dysfunction, vitamin deficiencies)

Treatment options for depression may include:

• Psychological therapies such as cognitive behavioural therapy (CBT), available through NHS Talking Therapies services (self-referral possible in many areas via the NHS website)

• Antidepressant medication if clinically indicated, which can generally be used alongside Mounjaro, though monitoring may be needed as tirzepatide slows gastric emptying and could affect absorption of some oral medications

• Lifestyle interventions including structured physical activity, sleep hygiene, and social connection

• Referral to specialist mental health services if symptoms are severe or complex

The decision about continuing Mounjaro should be individualised, weighing the benefits for diabetes control or weight management against any potential impact on mental wellbeing.

Monitoring Mental Health During Mounjaro Treatment

Proactive mental health monitoring is an important component of comprehensive care for anyone taking Mounjaro, particularly given the complex interplay between metabolic health, weight management, and psychological wellbeing.

Before starting Mounjaro:

Your healthcare professional should conduct a baseline assessment including discussion of mental health history, current stressors, and support systems. This establishes a reference point for detecting changes. Patients with known mental health conditions may benefit from informing their mental health team about starting new metabolic medication.

During treatment:

• Regular review appointments (typically every 3–6 months for diabetes, more frequently during dose titration) should include enquiry about mood and psychological wellbeing

• Healthcare professionals may use brief screening questions such as the PHQ-2 ("Over the past two weeks, how often have you felt down, depressed, or hopeless?" and "How often have you had little interest or pleasure in doing things?"), followed by the PHQ-9 if concerns are identified

• Patients should be encouraged to report mood changes between scheduled appointments rather than waiting

• Self-monitoring can be valuable—some patients find mood tracking apps or journals helpful for identifying patterns

Collaborative care approach:

Optimal outcomes require coordination between diabetes/weight management teams, primary care, and mental health services when needed. The NICE guidance on depression in adults (NG222) emphasises integrated care for people with physical and mental health comorbidities.

For healthcare professionals:

Maintaining a low threshold for depression screening in patients taking Mounjaro is prudent, particularly in those with risk factors. The PHQ-9 is a validated, brief tool suitable for primary care and specialist settings. Any concerning symptoms should prompt comprehensive assessment and appropriate intervention, with clear safety-netting advice provided to patients about when and how to seek help urgently if suicidal thoughts emerge.

Scientific References

1. Mounjaro KwikPen 10mg solution for injection in pre-filled pen - Summary of Product Characteristics (SmPC).
2. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 8-11 July 2024.
3. Assessment report - Mounjaro (SURPASS and SURMOUNT trials).
4. Depression in adults: treatment and management. NICE guideline NG222.
5. GLP-1 receptor agonists: reminder of the potential side effects and to be aware of the potential for misuse.

Frequently Asked Questions