Do Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) trigger seizures?

NSAIDs and Seizure Risk

NSAIDs generally do not trigger seizures in most patients, with the exception of mefenamic acid which has a significantly higher seizure risk. The risk of seizures with most NSAIDs is rare and primarily occurs in cases of substantial overdose or in patients with specific risk factors.

Evidence on NSAIDs and Seizure Risk

General Risk Assessment

• Most NSAIDs have minimal association with seizure activity at therapeutic doses
• Mefenamic acid is a notable exception, with seizures occurring in over one-third of overdose cases 1
• Seizures have been reported with other NSAIDs primarily in cases of:
  • Substantial overdose (particularly with ibuprofen)
  • Pre-existing seizure disorders
  • Significant electrolyte abnormalities

Specific NSAID Considerations

1. Mefenamic acid: Highest seizure risk among NSAIDs
2. Ibuprofen: Seizures rarely reported at therapeutic doses; may occur with massive ingestion (>400 mg/kg) 1
3. Naproxen: FDA labeling mentions seizures as a rare adverse effect (<1% of patients) 2

Risk Factors for NSAID-Related Seizures

Patients with the following conditions may have increased risk:

• Pre-existing seizure disorders: Guidelines note that patients with seizure disorders should be monitored closely when taking certain medications, including some NSAIDs 3
• Electrolyte disturbances: NSAIDs can contribute to hyponatremia in some patients, which may lower seizure threshold 4
• Renal impairment: Reduced clearance of NSAIDs may increase risk of adverse effects
• Overdose situations: Significantly higher risk of CNS effects including seizures 1

Clinical Implications

For Patients Without Seizure History

For most patients without a seizure history, NSAIDs can be used safely at therapeutic doses with minimal seizure risk. However:

• Monitor for neurological symptoms like dizziness, drowsiness, or confusion
• Be cautious with high doses or prolonged use
• Avoid mefenamic acid if seizure risk is a concern

For Patients With Seizure History

In patients with pre-existing seizure disorders:

• Use NSAIDs with caution and monitor closely for increased seizure activity 3
• Consider alternative pain management options if appropriate
• Avoid mefenamic acid due to its higher seizure risk 1

Management of NSAID-Related Neurological Effects

If neurological symptoms or seizures occur:

• Discontinue the NSAID immediately
• Provide supportive care
• Consider activated charcoal in overdose cases (within 1 hour of ingestion)
• Monitor electrolytes, particularly sodium levels
• Treat seizures according to standard protocols

Conclusion

While most NSAIDs have a low risk of triggering seizures at therapeutic doses, caution is warranted in patients with pre-existing seizure disorders, electrolyte abnormalities, or renal impairment. Mefenamic acid carries a significantly higher seizure risk compared to other NSAIDs and should be avoided in seizure-prone individuals.