Postmortem forensic toxicology of trazodone

Trazodone is a popular antidepressant medication that has been available fo r approximately 30 years. It has a reputation as a safe drug with relativel y few reported fatalities attributed solely to it. We review the pharmacolo gy and forensic toxicology of trazodone and report toxicology and cause and manner of death in a series of 37 deaths in which trazodone was detected. Although the normal upper therapeutic blood concentration for trazodone is about 2 mg/L, fatalities are rarely attributed solely to it at blood concen trations below 9 mg/L. Considering the pharmacology of the drug, potential interactions between other drugs with serotonin reuptake properties need to be considered, as does the increased susceptibility to the toxic effects i n patients with pw-existing heart disease. In the cases reviewed, none were attributed solely to trazodone, although t razodone was frequently present together with other serotonergic drugs, suc h as the selective serotonin reuptake inhibitors like fluoxetine and sertra line. Ten cases had blood trazodone concentrations above 2 mg/L. Of these c asts, trazodone played a primary role in the death of three subjects, with blood concentrations all greater than 9 mg/L. We confirm the conclusions of others that trazodone is a relatively safe dr ug except in massive overdose, although its toxicity may be influenced by t he presence of other drugs and underlying pathophysiology.