Has seizure been reported as an adverse effect of tramadol?

Tramadol and Seizure Risk

Yes, seizures have been definitively reported with tramadol use, and this is a well-established adverse effect that occurs even within recommended dosage ranges. The FDA has issued a black box warning specifically highlighting this risk. 1

FDA-Documented Seizure Risk

The FDA drug label explicitly warns that:

• Seizures have been reported in patients receiving tramadol within the recommended dosage range 1
• Seizure risk increases with doses above the recommended range 1
• The risk is further elevated when tramadol is combined with medications that lower seizure threshold, including SSRIs, SNRIs, tricyclic antidepressants, MAO inhibitors, other opioids, and neuroleptics 1
• In overdose situations, naloxone administration may paradoxically increase seizure risk 1

Clinical Practice Guidelines on Seizure Risk

Multiple clinical guidelines acknowledge tramadol's seizure-inducing properties:

• The 2024 World Society of Emergency Surgery guidelines state that tramadol may reduce the seizure threshold and is contraindicated in patients with a history of seizures 2
• The 2018 ESMO cancer pain guidelines note that tramadol can lower seizure thresholds, particularly in elderly patients 2
• The American Geriatrics Society recognizes that seizure risk increases with high doses or in predisposed patients 3

Clinical Evidence from Real-World Practice

Research studies have documented the occurrence and characteristics of tramadol-induced seizures:

• A 2009 cross-sectional study of 132 tramadol users found that 46.2% experienced seizures within 24 hours of tramadol ingestion, with all documented cases showing generalized tonic-clonic seizures 4
• Importantly, this study found no dose-dependent relationship - seizures occurred across all dose ranges, with the most common dose range being 500-1000 mg 4
• A 2019 Iranian study reported a 58% seizure prevalence among tramadol-intoxicated patients presenting to the emergency department 5
• A 2012 study found that 89% of tramadol-related seizures occurred within the first 24 hours of intake, with higher risk in patients concomitantly using alcohol, illicit drugs, antipsychotics, or antidepressants 6

High-Risk Populations and Scenarios

Patients at particularly elevated risk include:

• Those with a history of seizures (3.7-fold increased risk) 5
• Patients taking serotonergic medications (SSRIs, SNRIs, TCAs, MAOIs) due to additive effects 1, 2
• Individuals with epilepsy, head trauma, metabolic disorders, or undergoing alcohol/drug withdrawal 1
• Elderly patients, who are more vulnerable to CNS effects 2

Important Clinical Caveats

• The seizure risk is NOT strictly dose-dependent - seizures can occur even at therapeutic doses 4
• The combination of tramadol with serotonergic agents creates a dual risk: both seizures and potentially fatal serotonin syndrome 1, 2
• EEG abnormalities may be present acutely but often normalize within one week 6
• Most seizures are generalized tonic-clonic in nature 4, 6