Weight loss injections such as semaglutide (Wegovy) and liraglutide (Saxenda) have transformed obesity management in the UK, but questions remain about their impact on mental health. These glucagon-like peptide-1 (GLP-1) receptor agonists work throughout the body, including brain regions involved in mood and reward processing. Whilst clinical trials have not demonstrated significant psychiatric risks, post-marketing reports have prompted regulatory scrutiny. The MHRA and EMA continue to monitor safety signals, though no definitive causal link to serious mental health deterioration has been established. Understanding the evidence, recognising warning signs, and maintaining open communication with healthcare providers are essential for safe treatment.

How Weight Loss Injections Work in the Body

Weight loss injections licensed in the UK primarily refer to glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide (Wegovy) and liraglutide (Saxenda). These medications work by mimicking naturally occurring GLP-1 hormones in the body. They bind to GLP-1 receptors found throughout the body, including in the pancreas, gastrointestinal tract, and importantly, can exert effects on the brain through both direct and indirect pathways.

By activating these receptors, GLP-1 medications slow gastric emptying, which prolongs feelings of fullness after eating. They also influence appetite centres in the hypothalamus to reduce hunger signals, though the exact mechanisms vary between agents and may not require complete blood-brain barrier penetration.

The mechanism extends beyond simple appetite suppression. GLP-1 receptors are present in several brain regions involved in reward processing, mood regulation, and emotional responses to food. This neurological activity forms the basis for understanding how weight loss injections might potentially affect mental health, both positively and negatively.

These medications also improve glycaemic control by enhancing insulin secretion in response to meals and suppressing glucagon release. The resulting metabolic changes—including improved blood sugar stability—may indirectly influence overall wellbeing. However, the direct effects on neurotransmitter systems and brain chemistry remain an active area of research with evidence still emerging.

Key mechanisms include:

• Delayed gastric emptying and prolonged satiety

• Central nervous system appetite regulation

• Interaction with brain reward pathways

• Metabolic improvements affecting overall wellbeing

Reported Mental Health Side Effects and Evidence

The relationship between GLP-1 receptor agonists and mental health has received increased scrutiny following post-marketing surveillance reports. The Medicines and Healthcare products Regulatory Agency (MHRA) and European Medicines Agency (EMA) have reviewed cases of suicidal ideation and self-harm reported in patients taking these medications. However, both agencies have not established a definitive causal link, while continuing to monitor safety signals closely.

UK product information (SmPCs) for both Wegovy and Saxenda advise monitoring for mood changes and depression, and to discontinue treatment and seek medical advice promptly if suicidal thoughts occur.

Current evidence presents a complex picture. Some observational studies suggest that weight loss achieved through these medications may improve depressive symptoms and quality of life, likely due to enhanced self-esteem, increased mobility, and reduced obesity-related health complications. Conversely, isolated case reports and pharmacovigilance data have documented instances of new-onset depression, anxiety, and suicidal thoughts in some patients.

Clinical trial data from pre-marketing studies did not identify significant increases in psychiatric adverse events compared to placebo. However, these trials typically excluded individuals with serious mental health conditions, potentially limiting the generalisability of findings. Real-world evidence is now emerging as these medications are prescribed more widely to diverse patient populations.

Reported effects include:

• Potential mood improvements associated with weight loss

• Isolated reports of depression and anxiety

• Rare cases of suicidal ideation (causal link unconfirmed)

• Generally low incidence in clinical trials

Patients should be aware that whilst there is no official link established between these medications and serious mental health deterioration, individual responses vary considerably. The balance of current evidence suggests most people tolerate these medications well from a psychological perspective, but vigilance remains important.

If you experience any suspected side effects, report them to the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk or via the Yellow Card app).

Who Should Avoid Weight Loss Injections for Mental Health Reasons

Certain individuals may be at higher risk of experiencing mental health complications with weight loss injections and should approach treatment with particular caution. Those with a personal history of severe depression, bipolar disorder, or previous suicide attempts should have a thorough discussion with their GP or specialist before starting treatment. Whilst these conditions are not absolute contraindications, they warrant careful risk-benefit assessment and enhanced monitoring protocols.

Patients currently experiencing active suicidal ideation or severe psychiatric symptoms should not commence weight loss injections until their mental health is stabilised. The prescribing clinician should coordinate care with mental health services where appropriate. Additionally, individuals with a history of eating disorders—including anorexia nervosa, bulimia nervosa, or binge eating disorder—require specialist evaluation, as appetite-suppressing medications may exacerbate disordered eating patterns or psychological distress related to food and body image.

Younger patients represent another group requiring careful consideration. Semaglutide (Wegovy) is licensed for adolescents aged 12 and above with obesity in the UK, but should only be initiated within specialist paediatric weight management services as specified in the product information and NICE guidance (TA875). The developing brain may be more susceptible to neuropsychiatric effects, requiring additional monitoring.

Groups requiring caution or avoidance:

• Active severe depression or suicidal thoughts

• History of bipolar disorder or psychosis

• Current or previous eating disorders

• Adolescents (specialist supervision required)

• Patients with complex psychiatric conditions requiring coordinated care

Regarding pregnancy, semaglutide should be discontinued at least 2 months before a planned pregnancy. For liraglutide, the SmPC advises avoiding use in pregnancy and discontinuing if pregnancy occurs. Neither medication is recommended during breastfeeding due to limited safety data rather than confirmed harm.

Monitoring Your Mental Wellbeing During Treatment

Active self-monitoring and open communication with healthcare providers form the cornerstone of safe weight loss injection use. Patients should establish a baseline understanding of their typical mood, anxiety levels, and general psychological wellbeing before starting treatment. Keeping a simple diary or using a mood-tracking application can help identify subtle changes that might otherwise go unnoticed during the early weeks of therapy.

Specific warning signs warrant immediate medical attention. These include new or worsening depression, persistent feelings of hopelessness, thoughts of self-harm or suicide, severe anxiety or panic attacks, unusual irritability or agitation, and significant sleep disturbances. Patients experiencing any of these symptoms should contact their GP promptly—ideally within 24 hours—rather than waiting for a scheduled review appointment. In cases of acute suicidal thoughts, immediate help should be sought through NHS 111, the Samaritans (116 123), or emergency services.

Routine follow-up appointments should include mental health screening as standard practice. Regular reviews are typically conducted during dose escalation and as clinically indicated thereafter. NICE guidance (TA875 for semaglutide, TA664 for liraglutide) specifies that treatment should be discontinued if certain weight loss thresholds are not met at specified timepoints. These consultations provide opportunities to discuss not only physical side effects and weight loss progress but also psychological wellbeing. Screening tools such as the PHQ-9 (depression) or GAD-7 (anxiety) may be helpful to track mental health status.

Monitoring strategies include:

• Regular mood and anxiety self-assessment

• Scheduled GP reviews with mental health screening

• Involvement of family members who may notice changes

• Coordination with existing mental health services if applicable

• Prompt reporting of any concerning psychological symptoms

Patients should not discontinue treatment without medical guidance. While tapering is not specifically required according to product information, stopping treatment may lead to return of appetite and weight regain. If mental health concerns arise, the prescriber can adjust the dose, provide additional support, or discontinue treatment whilst exploring alternative weight management strategies.

Report any suspected side effects to the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk).

Frequently Asked Questions