Tramadol and new-onset seizures

To the Editor: Tramadol is a synthetic, centrally acting analgesic that was approved for use in Australia in 1998. Seizures have been reported in patients receiving the drug in overdose and, rarely, at the recommended dose.1-4 Over a one-year period, we observed a number of tramadol-associated seizures in the First Seizure Clinic at Austin Health, an outpatient service for rapid evaluation and diagnosis of patients with new-onset seizures.5

We evaluated 197 patients from April 2003 to April 2004. One hundred had alternative diagnoses to epileptic seizures: syncope (n = 56), convulsive syncope (n = 27), panic attacks (n = 3) and other events (n = 14).

Of 97 patients with confirmed seizures, 8 (5 male; median age, 34 years [range, 18–51 years]) were associated with tramadol (Box). Two patients who had received high doses of tramadol (600–750 mg/day [maximum recommended dose, 400 mg/day]) had developed seizures within 24–48 hours. Among the other six patients, who had received tramadol in the recommended dose range (50–300 mg/day), seizures had occurred 2–365 days after commencing therapy. Long-term psychotropic medication was taken by two patients. Seizures were generalised tonic–clonic seizures, without auras or focal features. No patient had a prior history of seizures, and none had a recurrence after they had ceased taking tramadol for a median of 9 months’ follow-up (range, 2–14 months). Electroencephalographic studies were normal in seven patients, with only one isolated sharp slow-wave in one patient. Computed tomography scans were all normal, and magnetic resonance imaging was normal in five patients.

Previous US studies suggest a relatively low risk of seizures with tramadol, unless it is taken by people with epilepsy or taken with other drugs that reduce the seizure threshold.2-4

Tramadol is now widely prescribed in Australia, with 1.65 million prescriptions for oral tramadol issued under the Pharmaceutical Benefits Scheme in 2003.6 The Australian Adverse Drug Reactions Advisory Committee had received 83 reports of convulsions associated with tramadol to March 2004, although in only three cases was the association classified as “certain”.

In our First Seizure Clinic, tramadol is the most frequently suspected cause of provoked seizures. We cannot calculate the exposure risk in our population, but the frequency of tramadol-related seizures suggests that they may be under-reported. It is important to consider tramadol as a possible cause of seizures — even when used at recommended doses. This may avoid inappropriate use of anti-epileptic drugs and unnecessary restrictions on driving and choice of vocation that might apply in cases of new-onset epilepsy.