From the Guidelines
NSAIDs generally do not significantly lower seizure threshold in most patients and can be used safely in people with epilepsy. When considering the relationship between seizure threshold and Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), it's essential to prioritize the most recent and highest quality evidence. According to the clinical policy approved by the ACEP board of directors in 2024 1, the focus is on managing adult patients presenting to the emergency department with seizures, but it does mention that prescribed and illicit substance use can lower the seizure threshold. However, NSAIDs are not specifically mentioned as a concern for lowering seizure threshold in this context.
Key Points to Consider
- Common NSAIDs like ibuprofen, naproxen, and aspirin have minimal impact on seizure risk at standard therapeutic doses.
- Certain NSAIDs, particularly those with COX-2 selectivity like celecoxib, may have a slightly higher theoretical risk of lowering seizure threshold, though this effect is still quite small in clinical practice.
- Acetaminophen is often considered the safest first-line option for pain management in patients with epilepsy, followed by standard NSAIDs at regular doses.
- For patients with poorly controlled epilepsy or those who have previously experienced seizures with NSAID use, it would be prudent to use the lowest effective dose for the shortest duration necessary.
Mechanism and Interactions
The mechanism behind any potential seizure threshold lowering by NSAIDs likely involves their effects on prostaglandin synthesis, which can influence neuronal excitability. Additionally, some NSAIDs may interact with certain anti-seizure medications, potentially affecting their blood levels, so monitoring for drug interactions is important when combining these medication classes. Given the information available and prioritizing morbidity, mortality, and quality of life, the use of NSAIDs in patients with epilepsy should be approached with caution, but they are not inherently contraindicated 1.
From the Research
Relationship Between Seizure Threshold and Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
- The relationship between seizure threshold and NSAIDs is complex and influenced by multiple factors, including the type of NSAID, dosage, and individual patient characteristics 2.
- Some studies suggest that NSAIDs may have a neuroprotective effect and reduce the incidence of seizures in certain animal models, but the evidence is inconclusive 2.
- In contrast, other studies have reported that NSAIDs may worsen seizure activity or have no effect on seizure control 2, 3.
- The use of NSAIDs has been associated with an increased risk of seizures, particularly in patients with a history of epilepsy or other conditions that may decrease seizure threshold 4, 3.
- The mechanism by which NSAIDs affect seizure threshold is not fully understood, but it may be related to their anti-inflammatory properties and inhibition of prostaglandin synthesis 2, 3.
Clinical Implications
- Patients with a history of seizures or other conditions that may decrease seizure threshold should be cautious when using NSAIDs, and their use should be carefully monitored 4, 3.
- The potential benefits and risks of using NSAIDs in patients with epilepsy or other seizure disorders should be carefully weighed, and alternative treatments should be considered when possible 2, 3.
- Further research is needed to fully understand the relationship between NSAIDs and seizure threshold, and to determine the safest and most effective treatment options for patients with epilepsy or other seizure disorders 2, 3.