Pharmacokinetics and Pharmacodynamics of Quetiapine in a Patient with a Massive Overdose

Abstract

We present a case of massive overdose with the atypical antipsychotic quetiapine in a 34-year-old woman (body weight 65 kg). At admission, approximately 2 to 4 hours after ingestion of approximately 24 g of quetiapine, the patient was comatose (Glasgow Coma Scale score 5), requiring orotracheal intubation and transfer to the intensive care unit. Because of myoclonic jerks and generalized seizures, benzodiazepines were administered. In addition to transient mild hypotension after intubation, the main cardiovascular manifestation was sinus tachycardia. The QT interval was normal, and the QTc interval (Bazett's correction) was maximally prolonged to 620 ms. However, no malignant arrhythmias were observed. The patient recovered within 2 days but remained agitated and aggressive, for which she was transferred to the psychiatric clinic. The pharmacokinetics of quetiapine in such a large overdose could not be described by simple first-order kinetics. The initially observed rapid decline of the plasma concentrations of quetiapine could be simulated by first-order kinetics (half life = 4.1 hr) and can most probably be explained by rapid distribution into tissues. The final elimination of the drug from the body occurred after approximately 34 hours at much slower rate, most probably reflecting redistribution from tissues into blood and consecutive hepatic clearance of the drug.

Intrahepatic Cholestasis Following Abuse of Powdered Kratom (Mitragyna speciosa)

“…Both hypotheses might explain why mitragynine was still detectable in the urine after 2 weeks. Prolongation of elimination half-life has been described after overdoses of therapeutic drugs [27,28]. Unfortunately, the liver biopsy was too small to be analyzed for its content of M. speciosa alkaloids.…”

Dosing Recommendations for Quetiapine When Coadministered With HIV Protease Inhibitors

“…Where reported, the outcomes of the 107 cases ranged from recovery to death. Recovery from coma was reported in 4 cases . In a report of 18 quetiapine overdose cases, the outcome was not reported with the exception of 1 patient who recovered .…”

“…A study of quetiapine acute overdose (n = 945 cases) reported 96 comas and 3 deaths (∼10% and 0.3% of cases, respectively) . In addition, several case reports of quetiapine overdose describe reversible comas . In the index coma case the possibility of overdose of quetiapine or other substances was not mentioned, and the outcome was not reported.…”

Delayed-Onset Seizure in a Mild Quetiapine Overdose: Report of a Case and Review of the Literature

“…Second, the delayed occurrence of a seizure following overdose incident is peculiar in light of the pharmacokinetics of quetiapine. Other reports of seizure place the timing at 4–8 hours following quetiapine overdose [2, 7]. Plasma concentration of quetiapine typically peaks at 1–1.5 hours, and its elimination half-life is approximately 6 hours [8, 9].…”