Combined effects of quetiapine and opioids: A study of autopsy cases, drug users and sedation in rats

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Fatal opioid poisonings often involve methadone or morphine. This study aimed toelucidate if quetiapine, a widely used sedative antipsychotic medication, may increasethe risk of fatal opioid poisoning by additive inhibitory effects on the central nervoussystem. We used data from 323 cases of fatal methadone or/and morphine poison-ings autopsied from 2013 to 2020, a survey of 34 drug users, and performed blindedplacebo-controlled studies in 75 Flinders Resistant Line rats receiving three cumula-tive intraperitoneal doses of vehicle, methadone (2.5, 10 and 15 mg/kg), morphine(3.75, 15 and 22.5 mg/kg), quetiapine (3, 10 and 30 mg/kg) or quetiapine combinedwith methadone or morphine. Quetiapine was detected in 20.4% of fatal opioid poi-sonings with a significantly increased frequency over time, primarily in low or thera-peutic concentrations, and was not associated with methadone or morphineconcentrations. Use of quetiapine, most commonly in low-to-moderate doses toobtain a sleep-inducing or tranquillizing effect, was reported by 67.6% of surveyrespondents. In the animal studies, a significant impairment of sedation score, perfor-mance on the rotarod and open field mobility was observed in all treatment groupscompared with vehicle. However, the effect of quetiapine plus the opioid was notsignificantly different from that of the opioid alone. Thus, no additive sedative effectswere observed in rats. Our results suggest that quetiapine is more often an innocentbystander than a contributor to fatal opioid poisoning. However, the combinedeffects on other parameters, including blood pressure, cardiac rhythm and respiratoryrate, need investigation.
Original languageEnglish
Article number e13214
JournalAddiction Biology (Online)
Publication statusPublished - Sept 2022


  • Forensic Toxicology
  • Opiates
  • Psychotic Disorders
  • drug effects
  • pharmacology


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