QT interval prolongation in acute antipsychotic poisoning: systematic review and recommendations

Antipsychotic medications are often associated with QT interval prolongation, which can lead to ventricular dysrhythmias, including torsade de pointes. However, unstable or significant dysrhythmic events are rare. Evidence-based recommendations on the assessment and management of poisoned patients at risk for QT interval prolongation are lacking. Current practice often involves costly and lengthy cardiac monitoring, leading to delayed disposition of the patient from emergency departments or prolonged monitoring times in other hospital units. To address this issue, the QT Interval Prolongation in Clinical Toxicology Workgroup was formed by the Clinical Toxicology Recommendations Collaborative to develop evidence-based recommendations for the management and treatment of QT interval prolongation in acute overdose patients. This article reports our findings on patients with antipsychotic poisoning.

A systematic review of the literature regarding QT interval prolongation in all acute overdoses was undertaken, and the evidence was summarized for antipsychotic medication overdose. Voting statements were drafted using a predetermined format for monitoring the QT interval and use of continuous cardiac monitoring. A two-round modified Delphi method was used to reach a consensus. The strength of consensus was measured using the disagreement index as defined by the RAND/UCLA Appropriateness Method.

From the 327 articles that were included in the systematic review of QT interval prolongation in all acute overdoses, a total of 55 articles were relevant to antipsychotic medication-induced QT prolongation in acute overdose. Medications with more than three articles were reviewed individually for recommendations, whilst medications with less than three were grouped together for discussion as miscellaneous. Individual medication recommendations were made for amisulpride (15 articles), thioridazine (11 articles), ziprasidone (eight articles) and quetiapine (13 articles), whilst consensus statements based on limited data were made for acute ingestions of clozapine, haloperidol, iloperidone, pimozide, pipamperone, olanzapine and risperidone (14 articles in total). The electrocardiogram is suggested as a risk assessment tool for ingestion of all antipsychotic medication. We recommend continuous cardiac monitoring for patients ingesting more than amisulpride 2 g, thioridazine 1 g, and ziprasidone 3 g. We suggest continuous cardiac monitoring for the above-mentioned medications for lower dose ingestions as well as for ingestions of haloperidol, iloperidone, pimozide and pipamperone. We do not suggest continuous cardiac monitoring for acute clozapine and risperidone poisoning, and do not recommend continuous cardiac monitoring for the QT interval in acute olanzapine or quetiapine poisoning. The need for ongoing cardiac monitoring should be guided by an individual risk assessment considering the medication and dose ingested, the time since ingestion, as well as other factors such as heart rate or co-ingestions.

The quality of evidence for the risk of QT interval prolongation and torsade de pointes is heterogeneous among different antipsychotics and inherently constrains the recommendations. Available data suggest that amisulpride, thioridazine and ziprasidone are associated with QT interval prolongation and torsade de pointes, while the risk is likely overstated for quetiapine, olanzapine and risperidone. Ongoing research is needed to improve management strategies for acute antipsychotic overdose-induced QT interval prolongation and dysrhythmias.

The QT Interval Prolongation in Clinical Toxicology Workgroup recommends the use of screening electrocardiograms in all patients with acute antipsychotic medication overdose and cardiac monitoring in patients with at-risk overdoses from thioridazine, amisulpride, and ziprasidone. The QT Interval Prolongation in Clinical Toxicology Workgroup suggests the same approach for patients with overdoses of haloperidol, iloperidone, pipamperone and pimozide. The risk of torsade de pointes is likely overstated for acute antipsychotic medication overdose as a general class group, and concern should rather focus on a few specific medications.