Does tramadol cause seizures? Is there an interaction between tricyclic antidepressants, selective

Fråga: Does tramadol cause seizures? Is there an interaction between tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and tramadol?

Sammanfattning: Tramadol may cause seizures in overdose or in therapeutic doses especially when predisposing factors exist, including use of tricyclic antidepressants and SSRIs.

There seems to be a possible interaction between these drugs and reports of seizures have been observed with concomitant drug treatment.

Svar: Tramadol is a centrally acting, synthetic, opioid analgesic. It has been shown to provide analgesia for both acute and chronic pain of mild to moderate severity. Although it is well tolerated, there are some CNS side-effects like drowsiness, vertigo, nausea, headache, somnolence, and seizures.

According to the FDA´s database of adverse drug events, there are 83 reports of seizures among patients using tramadol in the first year and over 200 reports in the second year of its marketing in USA (1). Seizures in 72 cases(54 per cent) occurred within one day following the initial dose and previous seizure history was only present in 9.7 per cent of subjects (1).

There are also some reports about tramadol induced seizures on Medline. A 2-year-old girl given 4 mg/kg of tramadol, which is an overdose for children, had a seizure 45 min after drug administration (2).

Seven cases of seizure activities related with overdose of tramadol use were found in the database of 7 poison centres in USA (3). The lowest dose associated with seizures was 500 mg. Seizure activity in tramadol overdose appears to be related to the inhibition of monoamine reuptake rather than the opioid effect (3).

During the temporary increases of the doses, two generalised seizures were observed in a 36-year-old female patient (4).

There are 3 seizure activities related to tramadol use reported to SADRAC (The Swedish Adverse Drug Reactions Advisory Committee) (5).

Although the majority of seizures is observed in patients receiving excessive doses of tramadol, it can also occur with therapeutic doses in patients with predisposing conditions, taking other medications known to lower the seizure threshold, such as tricyclic antidepressants, and SSRIs.

Concomitant medications with potential to increase seizure risk were taken in 58 per cent of the cases and included 22.6 per cent of tricyclic antidepressants as well as 16.1 per cent of SSRIs (1). This suggests a possible interaction between these drugs. Tramadol is metabolised to its major metabolite by CYP2D6 which is also the common pathway for the metabolism of the other mentioned drugs. The interaction between tramadol and SSRIs is well reported in a Drugline document (6).