Does tirzepatide (a dual GIP and GLP-1 receptor agonist) increase the risk of seizures?

Tirzepatide and Seizure Risk

Tirzepatide does not appear to increase the risk of seizures based on current evidence, though naltrexone/bupropion (another weight loss medication) carries this risk.

Safety Profile of Tirzepatide

Tirzepatide is a dual GIP/GLP-1 receptor agonist approved for the treatment of type 2 diabetes and obesity. When examining its safety profile:

• The most common adverse effects are gastrointestinal, including nausea, vomiting, diarrhea, and constipation 1
• These GI side effects are dose-dependent, with higher rates at 10mg and 15mg doses 2
• Discontinuation rates due to adverse events are highest with the 15mg dose (10%) 3

Neurological Safety

Current evidence regarding tirzepatide's neurological safety shows:

• No mention of seizures as a common adverse effect in major guidelines 1
• No increased risk of seizures reported in systematic reviews of tirzepatide safety 3, 2
• Only one case report describes autoimmune encephalitis with seizures following tirzepatide use, which appears to be extremely rare 4

Comparison with Other Weight Loss Medications

When comparing tirzepatide with other weight loss medications:

• Naltrexone/bupropion (Contrave) carries a known risk of seizures and is contraindicated in individuals with seizure disorders 1
• GLP-1 receptor agonists like semaglutide and liraglutide have not been associated with increased seizure risk 1
• Phentermine/topiramate has been associated with cognitive side effects but not specifically seizures 1

Clinical Considerations

When prescribing tirzepatide:

1. Medication selection:

   • For patients with a history of seizures, tirzepatide may be preferred over naltrexone/bupropion
   • Avoid naltrexone/bupropion in patients with seizure disorders, uncontrolled hypertension, or chronic opioid use 1

2. Monitoring:

   • Monitor for rare neurological symptoms including changes in consciousness, agitation, or speech impairment
   • The single case report of autoimmune encephalitis with seizures 4 suggests extreme rarity but vigilance for unusual neurological symptoms is prudent

3. Dose considerations:

   • Start with lower doses and titrate slowly to minimize adverse effects 1
   • Higher doses (10-15mg) have higher discontinuation rates due to adverse events 2

Special Populations

• Women of childbearing potential: Tirzepatide may reduce the bioavailability of oral hormonal contraceptives, requiring additional non-oral contraception methods for 4 weeks after initiation and dose escalations 1, 5
• Patients with kidney disease: Use with caution due to potential risk of acute kidney injury 5
• Patients with liver disease: Contraindicated in Child-Pugh C cirrhosis and should be used with caution in Child-Pugh B cirrhosis 5

In conclusion, while there is one isolated case report of seizures associated with tirzepatide 4, the comprehensive safety data from clinical trials and systematic reviews does not indicate an increased seizure risk with tirzepatide use. For patients with a history of seizures who need weight management medication, tirzepatide appears to be a safer choice than naltrexone/bupropion.