Incidence of Corrected QT Prolongation With Concomitant Methadone and Atypical Antipsychotics in Critically Ill
Insights
This pilot study found no significant difference in QTc prolongation when adding atypical antipsychotics to methadone in pediatric intensive care unit (PICU) patients. Further research is needed to confirm safety in this population.
Area of Science:
- Pediatric critical care medicine
- Clinical pharmacology
- Cardiology
Background:
- Methadone and atypical antipsychotics are commonly used in pediatric intensive care units (PICUs).
- Both drug classes have potential risks for QTc interval prolongation.
- The safety of their combined use in pediatric patients requires careful evaluation.
Purpose of the Study:
- To assess the safety of combining methadone with atypical antipsychotics in PICU patients.
- To determine the incidence and risk factors for QTc interval prolongation in this patient group.
Main Methods:
- Retrospective observational pilot study in a single-center PICU.
- Included children aged 1 month to 18 years receiving methadone followed by an atypical antipsychotic (quetiapine or risperidone).
- EKG monitoring before and after medication initiation was performed.
Main Results:
- QTc prolongation occurred in 5 of 34 patients (14.7%).
- Patients with QTc prolongation were older ( > 12 years) and heavier (median 91.3 kg).
- Quetiapine was associated with a higher incidence of QTc prolongation (23%) compared to risperidone (9.5%).
Conclusions:
- The addition of atypical antipsychotics to methadone in PICU patients did not result in a clinically significant increase in QTc prolongation.
- While some QTc prolongation was observed, particularly with quetiapine in older, heavier children, the overall incidence suggests a manageable risk profile.
- Further investigation is warranted to fully elucidate the safety of this drug combination in pediatric critical care settings.
Objective:
To evaluate the safety of the combination of methadone and an atypical antipsychotic in PICU patients.
Methods:
This was a retrospective observational cohort pilot study in a single-center PICU in an academic children's hospital. Children 1 month to 18 years of age were included if they received methadone, were then initiated on an atypical antipsychotic (i.e., quetiapine or risperidone), and had EKG monitoring before and after medication initiation.
Results:
Prolongation of the corrected QT (QTc) interval occurred in 5 of the 34 included patients when an atypical antipsychotic was added to methadone. Of the 5 patients who had a prolonged QTc interval, 4 (80%) were older than 12 years and had a median weight of 91.3 kg. There were statistical differences between age and weight when comparing patients who experienced QTc prolongation, but no differences in sex, ethnicity, electrolyte deficiencies, number of additional QTc-prolonging medications, and number of additional drug-drug interactions were identified. When comparing atypical antipsychotics, 9.5% of patients receiving risperidone had a prolonged QTc interval, versus 23% of patients receiving quetiapine (p = 0.04). The net change in QTc interval after initiation of methadone was 0.19 milliseconds (IQR: -3, 15), which increased after atypical antipsychotic initiation to 4 milliseconds (IQR: -16, 15).
Conclusions:
Our pilot trial suggests there is no clinically significant difference in incidence of QTc prolongation with addition of atypical antipsychotics to methadone.
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