What considerations should be taken for a patient with a history of depression who is prescribed Mounjaro (tirzepatide) for type 2 diabetes?

Mounjaro Does Not Cause Depression

There is no evidence that Mounjaro (tirzepatide) causes depression, and it can be safely prescribed to patients with a history of depression with appropriate monitoring. The available evidence shows psychiatric adverse events with GLP-1 receptor agonists are rare, and standard depression screening protocols should be followed regardless of tirzepatide use.

Evidence on Psychiatric Safety of Tirzepatide

The most comprehensive pharmacovigilance analysis of GLP-1 receptor agonists found that psychiatric adverse events comprised only 1.2% of total reports for semaglutide, liraglutide, and tirzepatide combined 1. Importantly, tirzepatide specifically had the lowest number of reports (740 total adverse events, representing only 2.3% of all reports) 1. Depression was the most commonly reported psychiatric event across all three medications, but this does not establish causation—patients with diabetes have inherently higher rates of depression regardless of medication 1.

The SURPASS clinical trial program (phases 1-5) evaluating tirzepatide safety and efficacy did not identify depression as a significant adverse event, with the medication demonstrating a safety profile similar to the GLP-1 receptor agonist class 2. Real-world studies involving 1,896 patients showed no concerning psychiatric safety signals over median follow-up of 10.4 months 3.

Standard Depression Screening in Diabetes

All patients with diabetes require annual depression screening regardless of which glucose-lowering medication they receive 4. This is a universal recommendation, not specific to tirzepatide:

• Conduct at least annual screening of depressive symptoms in all people with diabetes using age-appropriate, validated depression screening measures 4
• Screen more frequently among those with a self-reported history of depression 4
• Beginning at diagnosis of complications or when there are significant changes in medical status, consider assessment for depression 4

The rationale is clear: elevated depressive symptoms and depressive disorders affect approximately one in four people with type 1 or type 2 diabetes, with women having significantly higher rates than men 4. History of depression, current depression, and antidepressant medication use are actually risk factors for developing type 2 diabetes itself, especially with other risk factors like obesity 4.

Clinical Management Approach

For a patient with depression history being prescribed tirzepatide:

Baseline Assessment:

• Verify current depression status using validated screening measures (PHQ-9 or similar) 4
• Document current antidepressant regimen if applicable 4
• Assess for active suicidal ideation, particularly in patients under 24 years on antidepressants 4

Ongoing Monitoring:

• Continue annual depression screening as standard diabetes care 4
• Monitor at 1-2 weeks after initiating any new antidepressant (not related to tirzepatide) 5
• Reassess depression symptoms at routine diabetes visits 4

Treatment Integration:

• If depression treatment is needed, refer to qualified behavioral health professionals with experience using evidence-based approaches (cognitive behavioral therapy, interpersonal therapy) in conjunction with collaborative care 4
• Reevaluate the diabetes treatment regimen if depressive symptoms worsen, as this may reflect disease burden rather than medication effect 4

Potential Benefits of GLP-1 Receptor Agonists

Interestingly, GLP-1 receptor agonists may actually help with certain eating behaviors that can accompany depression. These medications help regulate hunger and food intake, potentially reducing uncontrollable hunger and bulimic symptoms that can occur in patients with diabetes 4. This is particularly relevant since binge eating (excessive food intake with loss of control) is the most commonly reported disordered eating behavior in people with type 2 diabetes 4.

Common Pitfalls to Avoid

Do not attribute new or worsening depression to tirzepatide without considering other factors:

• Diabetes distress and reduced quality of life from disease burden are common 4
• Comorbid psychiatric disorders are prevalent in diabetes populations independent of medications 4
• Other medications (particularly atypical antipsychotics if prescribed) have stronger associations with metabolic and psychiatric effects 4

Do not delay tirzepatide initiation in patients with well-controlled depression:

• The metabolic benefits (HbA1c reduction of 1.87-2.59% and weight loss of 6.2-12.9 kg) are substantial 2
• Real-world data confirms clinically significant A1C reduction of 1.02% and weight loss of 7.3 kg 3
• These improvements in glycemic control and weight may actually improve overall well-being and reduce diabetes distress 4

Monitor for medication-specific psychiatric risks from other agents:

• Second-generation antipsychotics (olanzapine, etc.) require screening for diabetes and close monitoring if prescribed 4
• Screen patients on atypical antipsychotics for prediabetes/diabetes at 4 months after initiation and annually thereafter 4