Naproxen and Seizure Risk
Naproxen at therapeutic doses carries minimal seizure risk in patients without predisposing factors, but massive overdose can cause seizures as part of severe toxicity including metabolic acidosis. 1, 2
Therapeutic Dose Safety Profile
At standard therapeutic doses, naproxen does not have a clinically significant association with seizure induction. 3
The American Family Physician guidelines identify central nervous system effects of NSAIDs as rare, with aseptic meningitis being the most notable CNS complication specifically associated with naproxen (particularly in lupus patients), but seizures are not listed among the common adverse CNS effects at therapeutic doses. 3
In experimental epilepsy models, naproxen actually demonstrated protective effects against seizure activity when tested in pentylenetetrazole-induced kindling, suggesting COX inhibition may have neuroprotective rather than proconvulsant properties at appropriate doses. 4
Overdose-Related Seizure Risk
Massive naproxen overdose (70g ingestion) has been documented to cause seizures as part of a severe toxicity syndrome that includes metabolic acidosis, altered mental status, and potential renal impairment requiring dialysis. 1
A case report of a 15-year-old with acute naproxen sodium ingestion demonstrated seizures occurring rapidly after overdose in conjunction with severe metabolic acidosis, with recovery correlating to naproxen pharmacokinetics over 12 hours. 2
Drug-induced seizures from analgesics are recognized in the literature, with approximately 6.1% of first-occurring seizures being drug-induced, though this encompasses many medication classes beyond NSAIDs. 5
Clinical Context and Risk Stratification
Risk factors for drug-induced seizures include: history of epilepsy, blood-brain barrier dysfunction, neurological diseases, extremes of age, liver/kidney impairment, and polypharmacy—not the drug naproxen itself at therapeutic doses. 5
The experimental evidence suggests NSAIDs may have variable effects depending on the epilepsy model, with some showing neuroprotection and reduced seizure activity, while others show worsening—but these are research contexts, not clinical therapeutic use. 6
Practical Recommendations
For routine therapeutic use in patients without seizure history or massive overdose, naproxen does not require specific seizure-related precautions. 3, 7
In overdose situations presenting with altered mental status, anticipate potential seizure activity and prepare for supportive management including benzodiazepines, correction of metabolic acidosis, and consideration of renal replacement therapy for severe cases. 5, 1
Young, healthy patients using short-term naproxen (3-day courses) face minimal CNS risk, as most NSAID complications occur with prolonged use or in high-risk populations. 7