Can Mounjaro (tirzepatide) cause aggression, stress, anxiety, and stomach discomfort in a patient with a history of cardiovascular disease or type 2 diabetes, who is also taking Amlodipine (amlodipine besylate)?

Can Mounjaro Cause Aggression, Stress, Anxiety, and Stomach Discomfort?

Mounjaro (tirzepatide) is not associated with aggression, stress, or anxiety as documented adverse effects in clinical trials, but gastrointestinal symptoms including stomach discomfort are common, occurring in 13-22% of patients, particularly during dose escalation. 1, 2

Gastrointestinal Symptoms: Well-Established Side Effects

The most common adverse effects of tirzepatide are gastrointestinal in nature and include:

• Nausea occurs in 12-23% of patients taking tirzepatide, compared to only 2% with comparator agents 1
• Diarrhea affects 13-22% of patients on tirzepatide versus 4% on comparators 1
• Decreased appetite occurs in 9-11% of tirzepatide users 1
• Vomiting affects 5-9% of patients on tirzepatide 1
• Most gastrointestinal symptoms are mild to moderate and occur predominantly during the dose-escalation phase, typically resolving over time 1, 2

The stomach discomfort your patient is experiencing is consistent with the known gastrointestinal side effect profile of Mounjaro and represents a documented adverse effect of this medication.

Psychiatric Symptoms: No Established Association

There is no documented evidence linking tirzepatide to aggression, stress, or anxiety in any of the major clinical trials. 1, 3, 2

• The SURPASS clinical trial program (SURPASS 1-5), which enrolled thousands of patients with type 2 diabetes, did not report aggression, stress, or anxiety as adverse effects of tirzepatide 2
• The SURPASS-4 trial, which included 1,995 participants treated with tirzepatide for up to 104 weeks, documented comprehensive safety data without identifying psychiatric symptoms as treatment-related adverse events 1
• The recent SURPASS-CVOT trial involving 13,299 patients showed a similar safety profile to GLP-1 receptor agonists, with no psychiatric adverse effects reported 3

Alternative Explanations to Consider

Given the absence of evidence linking tirzepatide to psychiatric symptoms, alternative explanations should be explored:

Hypoglycemia-Related Symptoms

• Patients on amlodipine with cardiovascular disease may have other medications that interact with tirzepatide 4
• If the patient is on any insulin secretagogues (sulfonylureas or glinides) not mentioned in the history, hypoglycemia could manifest as irritability, anxiety, and feeling on edge 4, 5
• Blood glucose monitoring should be performed to rule out hypoglycemic episodes 5, 6

Gastrointestinal Distress as Primary Driver

• Chronic nausea and stomach discomfort can secondarily cause irritability, stress, and anxiety through persistent physical discomfort 1
• The temporal relationship between starting Mounjaro and symptom onset, combined with documented GI side effects, suggests the stomach symptoms are medication-related, which may be contributing to psychological distress 1, 2

Cardiovascular Considerations

• The patient is on amlodipine, suggesting underlying cardiovascular disease or hypertension 4
• Amlodipine itself can cause dizziness, fatigue, and somnolence, which could contribute to feeling "on edge" 4
• Tirzepatide has demonstrated cardiovascular safety with no increased risk of major adverse cardiovascular events 1, 3

Clinical Recommendations

For the gastrointestinal symptoms:

• These are expected adverse effects that typically improve after the dose-escalation phase 1, 2
• Consider slower dose titration if symptoms are severe 2
• Reassure the patient that most GI symptoms are mild to moderate and resolve over time 1

For the psychiatric symptoms:

• These are not attributable to Mounjaro based on available evidence 1, 3, 2
• Evaluate for hypoglycemia, particularly if the patient is on any insulin or insulin secretagogues 4, 5
• Consider whether chronic GI discomfort is contributing to psychological distress 1
• Assess for other life stressors, medication interactions, or underlying psychiatric conditions that may have coincidentally emerged 4
• Monitor blood pressure and cardiovascular status given the patient's use of amlodipine 4, 5

Regarding the medical certificate:

• The stomach discomfort can be attributed to Mounjaro as a documented adverse effect 1
• The aggression, stress, and anxiety cannot be attributed to Mounjaro based on current evidence and require alternative evaluation 1, 3, 2