Methadone maintenance, QTc and torsade de pointes: Who needs an electrocardiogram and what is the prevalence of QTc prolongation?

Abstract

High-dose methadone has been associated with rate-corrected QT (QTc) prolongation and 'torsade de pointes'. The Medicines and Healthcare products Regulatory Agency (MHRA) advise electrocardiograms (ECGs) for patients on methadone with heart/liver disease, electrolyte abnormalities, concomitant QT prolonging medications/CYP3A4 inhibitors or prescribed methadone >100 mg daily. The percentage of patients fulfilling MHRA criteria for ECG monitoring and prevalence of QT prolongation in patients who had an ECG was assessed. A cross-sectional study of opioid-dependent patients prescribed opioid maintenance that completed a screening questionnaire prior to referral for an ECG. MHRA criteria were assessed in the referred group. The automated QTc score was analysed with methadone dose, substance use and QT risk factors. Of 155 patients screened; 57.4% (n = 89) fulfilled MHRA criteria for ECG monitoring (75.5% (n = 117) if cocaine included as QT prolonging drug). Eighty-three (53.5%) had ECGs; 19.3% (n = 16) prescribed QT prolonging medication, 22.9% (n = 19) prescribed >100 mg methadone and 47% (n = 39) used cocaine. Mean QTc interval was 429.0 ms (SD 26.4, 351-489). Eighteen per cent exceeded QTc gender-specific thresholds (≥450 ms men and≥470 ms women). Linear regression found total daily methadone dose (β = 0.318, P = 0.003) and stimulant use (β = -0.213, P = 0.043) predictive of QTc length. Over half to three-quarters of methadone maintenance patients fulfilled MHRA criteria for ECG monitoring, which has costly implications. QTc prolongation prevalence was 18.1% with no 'clinically significant' QTc prolongation >500 ms or torsade de pointes known to be present. Methadone dose and stimulant use were associated with longer QTc intervals. Further research on the clinical management of QTc prolongation with methadone is required.