Dose-independent occurrence of seizure with tramadol.
BACKGROUND
Tramadol, as a centrally-acting, opioid-like analgesic with serotonin reuptake inhibition property, is one of the most prescribed analgesics in the world. We assessed the incidence of seizure, as it is one of the most important adverse effects.


METHODS
In a cross-sectional study, 215 cases of tramadol users or abusers who were admitted to Loghman-Hakim Hospital Poisoning Center (LHHPC) in Tehran during a 5-month period, from April 2007 to September 2007, were assessed to evaluate the occurrence of seizure. Patients with positive history of co-ingestion of other drugs, addiction, convulsive disorders, renal diseases, or head trauma with abnormal electroencephalography (EEG) or computerized tomography (CT) scan of the brain were excluded, thus 132 patients were included in the study. For patients who had seizure, CT scan of the brain and EEG were performed, and frequency and type of seizure were identified. Mean tramadol dose was compared between patients with and without seizure.


RESULTS
Among the patients, 97 (73.5%) were male. Seizure occurred in 61 patients (46.2%) within 24 hours after tramadol ingestion. The majority of patients who had seizure were male (male, 83.6% vs. female, 16.4%). Mean tramadol dose was lower among females than males (males, 2413 mg vs. females, 1706 mg), but the difference was not statistically significant. Of 35 patients with documented seizure type, all showed generalized tonic-clonic seizure and 12 patients had abnormal EEG (35.3%). No statistically significant difference was observed in mean tramadol intake between patients with or without seizure. Analysis of patients with seizure, according to tramadol intake, indicated that most patients used tramadol in the dose range of 500-1000 mg followed in occurrence by 1500-2000 mg, then 100-500 mg, 2500-3000 mg, and 3500-4000 mg.


CONCLUSIONS
Mean tramadol intake does not differ between patients with and without seizure, and the most common dose range in those with seizure is 500-1000 mg. We thus conclude that the incidence of seizure with tramadol is not dose dependent.
Toxicological Research Center, and Poison Center, Loghman-Hakim Hospital, School of Medicine; Shaheed Beheshti University of Medical Sciences, Tehran, Iran.
Haleh
H
Talaie
Reyhaneh
R
Panahandeh
Mohammad
M
Fayaznouri
Zahra
Z
Asadi
Mohammad
M
Abdollahi
D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012640:Seizures / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D014057:Tomography, X-Ray Computed; D014147:Tramadol / Q000009:adverse effects*; D055815:Young Adult
D000701:Analgesics, Opioid; D014147:Tramadol