Acute Quetiapine Intoxication: Relationship Between Ingested Dose, Serum Concentration and Clinical Presentation-Structured Literature Review and Analysis

Abstract

Over the past decade, quetiapine has become one of the most commonly used psychotropic drugs in acute intoxication events worldwide. A structured literature review and analysis were conducted to assess the relationship between the kinetic and dynamic profiles in acute quetiapine intoxication. The correlation between dose and peak serum concentration (c_max) was determined using Pearson's correlation coefficient. Binary logistic regression was used to evaluate dose and c_max as predictors of the most common clinical events, signs and symptoms. One hundred and thirty-four cases of acute quetiapine ingestion were included in the analysis, with a median ingested dose of 10 g and a median c_max of 4 mg/L. The typical half-life was estimated to be 16.5 h, significantly longer than at therapeutic doses. For the immediate-release formulation, a biphasic disposition could not be excluded. Dose and c_max demonstrated a weak but significant correlation (r = 0.256; N = 63; p = 0.043). Central nervous system depression and tachycardia were the most common clinical signs. Higher doses and concentrations increased the risk of severe intoxication and were good predictors of intubation, tachycardia, hypotension, QT_c prolongation and seizures, but not QRS prolongation, arrhythmia, heart block, hypokalaemia or acidosis. The thresholds for dose and c_max that increased the risk for individual signs and symptoms varied widely. However, doses > 3 g or c_max > 2 mg/L can be considered as alert levels that represent a high risk for severe clinical course of acute quetiapine intoxication.

Keywords: intoxication; quetiapine; toxicodynamics; toxicokinetics.

Figure 1

Observed dose-normalised quetiapine concentration vs. time (decontamination/no decontamination). Dashed lines are fitted monoexponential curves.

Figure 2

Observed dose-normalised quetiapine concentration versus time (immediate-release/extended-release formulation). Dashed lines are fitted monoexponential curves.

Figure 3

Lowest Glasgow Coma Scale score—case distribution by dose and peak concentration.

Figure 4

Toxicodynamic parameters vs. ingested quetiapine dose boxplot. Circles denote outlyers by Tukey’s test.

Figure 5

Toxicodynamic parameters vs. quetiapine peak serum concentration boxplot. Circles denote outlyers by Tukey’s test.