Quetiapine and other antipsychotics combined with opioids in legal autopsy cases: A random finding or cause of fatal outcome?

Opioid poisoning is a frequent cause of death in drug addicts and occurs with opioid treatment. Quetiapine is often found in forensic autopsies and may increase the risk of fatal opioid poisoning by enhancing sedation, respiratory depression, hypotension and QT prolongation. We systematically searched for studies of acute toxicity of quetiapine or other antipsychotics combined with morphine or methadone. Case reports describing toxicity of quetiapine combined with morphine or methadone were also included. We retrieved one human study that observed pharmacokinetic interaction between quetiapine and methadone, and 16 other human studies. Fourteen investigated the combination of droperidol and morphine in treatment doses, and some indicated an additive sedative effect. Five animal studies with acepromazine in combination with morphine or methadone were located and indicated an additive effect on sedation and hypotension. Six forensic case reports in which death could have been caused solely by quetiapine, the opioid, or other drugs were found. Thus, acute toxicity of quetiapine combined with morphine or methadone has not been studied. Because of quetiapine's effects on alpha-adrenoceptors, muscarinic and histamine receptors, human ether-a-go-go-channels and methadone kinetics, we suggest further research to clarify if the indicated additive effects of opioids and droperidol or acepromazine are also true for quetiapine.