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Drug-Induced Long QT in Adult Psychiatric Inpatients: The 5-Year Cross-Sectional ECG Screening Outcome in Psychiatry Study
François R. Girardin, M.D., M.Sc.; Marianne Gex-Fabry, Ph.D.; Patricia Berney, M.D.; Dipen Shah, M.D.; Jean-Michel Gaspoz, M.D., M.Sc.; Pierre Dayer, M.D.
Am J Psychiatry 2013;170:1468-1476. doi:10.1176/appi.ajp.2013.12060860
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Dr. Shah has received research grants, speakers honoraria, consultant fees, stock options, or scientific advisory board honoraria from Biosense Webster, Biotronik, Endosense, and St. Jude. The other authors report no financial relationships with commercial interests.

The ECG Screening Outcome in Psychiatry (ESOP) study was supported by the Department of Anesthesiology, Intensive Care, and Clinical Pharmacology and Toxicology (University Hospitals of Geneva). Some inpatients were included in the Swiss Hepatitis C Cohort Study funded by the Swiss National Science Foundation (3347C0-108782/1), the Swiss Federal Office for Education and Sciences (03.0599), and the European Commission (LSHM-CT-2004-503359; VIRGIL Network of Excellence on Antiviral Drug Resistance).

From the Division of Clinical Pharmacology and Toxicology, the Medical and Quality Directorate, the Department of Community Medicine, Primary Care and Emergency Medicine, the Department of Mental Health and Psychiatry, and the Division of Cardiology, University Hospitals of Geneva and Geneva University, Geneva, Switzerland.

Address correspondence to Dr. Girardin (francois.girardin@hcuge.ch).

Presented in part at the Swiss-Western Annual Meeting of Psychiatry, Geneva, Switzerland, June 14th, 2012.

Copyright © 2013 by the American Psychiatric Association

Received June 30, 2012; Revised November 30, 2012; Revised March 19, 2013; Accepted May 17, 2013.

Abstract

Objective  The authors aimed to determine the prevalence of drug-induced long QT at admission to a public psychiatric hospital and to document the associated factors using a cross-sectional approach.

Method  All ECG recordings over a 5-year period were reviewed for drug-induced long QT (heart-rate corrected QT ≥500 ms and certain or probable drug imputability) and associated conditions. Patients with drug-induced long QT (N=62) were compared with a sample of patients with normal ECG (N=143).

Results  Among 6,790 inpatients, 27.3% had abnormal ECG, 1.6% had long QT, and 0.9% qualified as drug-induced long QT case subjects. Sudden cardiac death was recorded in five patients, and torsade de pointes was recorded in seven other patients. Relative to comparison subjects, patients with drug-induced long QT had significantly higher frequencies of hypokalemia, hepatitis C virus (HCV) infection, HIV infection, and abnormal T wave morphology. Haloperidol, sertindole, clotiapine, phenothiazines, fluoxetine, citalopram (including escitalopram), and methadone were significantly more frequent in patients with drug-induced long QT. After adjustment for hypokalemia, HCV infection, HIV infection, and abnormal T wave morphology, the effects of haloperidol, clotiapine, phenothiazines, and citalopram (including escitalopram) remained statistically significant. Receiver operating characteristic curve analysis based on the number of endorsed factors per patient indicated that 85.5% of drug-induced long QT patients had two or more factors, whereas 81.1% of patients with normal ECG had fewer than two factors.

Conclusions  Drug-induced long QT and arrhythmia propensity substantially increase when specific psychotropic drugs are administered to patients with hypokalemia, abnormal T wave morphology, HCV infection, and HIV infection.

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FIGURE 1. Patient Inclusion in a Study of Drug-Induced Long QT in Adult Psychiatric Inpatients

FIGURE 2. Receiver Operating Characteristic Curves for Distinguishing Between Patients With Drug-Induced Long QT and Normal ECGa

a Curves are built as a function of the number of endorsed factors among four clinical conditions (hypokalemia, hepatitis C virus infection, HIV, and abnormal T wave morphology) and seven drugs (clotiapine, haloperidol, phenothiazines, sertindole, citalopram, fluoxetine, and methadone). Area under the curve was 0.78 (95% CI=0.71–0.84) when only clinical conditions were counted (dashed line, open symbols) and 0.89 (95% CI=0.84–0.94) when taking into account clinical conditions and medication (solid line, closed symbols). The cutoff value (triangle) that maximized the sum of sensitivity and specificity was two factors, with 85.5% sensitivity (drug-induced long QT patients with two or more factors) and 81.1% specificity (normal ECG patients with fewer than two factors).

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TABLE 1.Characteristics of Patients With Torsade de Pointes (N=7) and Sudden Death (N=5)
Table Footer Note

a HCV=Hepatitis C virus.

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TABLE 2.Characteristics of Patients With and Without Drug-Induced Long QT at Admission to the Psychiatric Hospital
Table Footer Note

a Fisher-Boschloo’s exact unconditional test with Berger-Boos correction for binary variables; Mann-Whitney U test for other variables.

Table Footer Note

b Drug-induced long QT, N=61; normal ECG, N=140.

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TABLE 3.Univariate and Multivariate Analysis of Drugs Associated With Long QT at Admission to the Psychiatric Hospital
Table Footer Note

a All drugs administered to at least 10 patients are listed, except for sertindole (N=9).

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b Arizona Center for Education and Research on Therapeutics (http://www.azcert.org/).

Table Footer Note

c Logistic regression model, adjusted for hypokalemia, hepatitis C virus infection, HIV infection, and abnormal T wave morphology.

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