Lethal combination of tramadol and multiple drugs affecting serotonin

The death of a 36-year-old alcoholic man who died after developing seizure activity while being treated with tramadol, as well as with venlafaxine, tr azodone, and quetiapine, all of which interact with the neurotransmitter se rotonin, is reported. The decedent, who had a history of chronic back pain, alcoholism, depression, mild hypertensive cardiovascular disease, and gast ritis, had just been discharged from the hospital after 4 days of alcohol d etoxification treatment. During the admission, no withdrawal seizures were noted. The morning after discharge, a witness observed the decedent exhibit ing seizure activity and then collapsing. An autopsy was performed approxim ately 6 hours after death, and the anatomic findings were consistent with s eizure activity and collapse, which included biting injuries of the tongue and soft-tissue injuries of the face. Toxicologic analysis identified trama dol, venlafaxine, promethazine, and acetaminophen in the urine; tramadol (0 .70 mg/L) and venlafaxine (0.30 mg/L) in the heart blood, and 0.10 mg of tr amadol in 40 mi of submitted stomach contents. No metabolites, such as acet ate, acetone, lactate, and pyruvate, were found in the specimens that would be characteristically found in a person with alcohol withdrawal syndrome. The threshold for seizures is lowered by tramadol. Ln addition, the risk fo r seizure is enhanced by the concomitant use of tramadol with selective ser otonin reuptake inhibitors or neuroleptics, and its use in patients with a recognized risk for seizures, i.e., alcohol withdrawal. The cause of death in this individual was seizure activity complicating therapy for back pain, depression, and alcohol withdrawal syndrome. The data in Adverse Event Rep orting System of the Food and Drug Administration from November 1, 1997 to September 8, 1999 was reviewed along with a MEDLINE search from 1966 to the present. This case appears to be the first reported death caused by seizur e activity in a patient taking tramadol in combination with drugs that affe ct serotonin.