Prevalence and clinical relevance of corrected QT interval prolongation during methadone and buprenorphine treatment: a mortality assessment study.
OBJECTIVE
To determine the prevalence of corrected QT interval (QTc) prolongation among patients in opioid maintenance treatment (OMT) and to investigate mortality potentially attributable to QTc prolongation in the Norwegian OMT programme.


METHODS
Two hundred OMT patients in Oslo were recruited to the QTc assessment study between October 2006 and August 2007. The Norwegian register of all patients receiving OMT in Norway (January 1997-December 2003) and the national death certificate register were used to assess mortality. Mortality records were examined for the 90 deaths that had occurred among 2382 patients with 6450 total years in OMT.


METHODS
The QTc interval was assessed by electrocardiography (ECG). All ECGs were examined by the same cardiologist, who was blind to patient history and medication. Mortality was calculated by cross-matching the OMT register and the national death certificate register: deaths that were possibly attributable to QTc prolongation were divided by the number of patient-years in OMT.


RESULTS
In the QTc assessment sample (n = 200), 173 patients (86.5%) received methadone and 27 (13.5%) received buprenorphine. In the methadone group, 4.6% (n = 8) had a QTc above 500 milliseconds; 15% (n = 26) had a QTc interval above 470 milliseconds; and 28.9% (n = 50) had a QTc above 450 milliseconds. All patients receiving buprenorphine (n = 27) had QTc results <450 milliseconds. A positive dose-dependent association was identified between QTc length and dose of methadone, and all patients with a QTc above 500 milliseconds were taking methadone doses of 120 mg or more. OMT patient mortality, where QTc prolongation could not be excluded as the cause of death, was 0.06/100 patient-years. Only one death among 3850 OMT initiations occurred within the first month of treatment.


CONCLUSIONS
Of the methadone patients, 4.6% had QTc intervals above 500 milliseconds. The maximum mortality attributable to QTc prolongation was low: 0.06 per 100 patient-years.
Anchersen
Katinka
K
University of Oslo, Institute of Psychiatry, Norwegian Centre for Addiction Research (SERAF), Kirkeveien, Oslo, Norway. katinka.anchersen@medisin.uio.no
Clausen
Thomas
T
Gossop
Michael
M
Hansteen
Viggo
V
Waal
Helge
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002047:Buprenorphine / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000401:mortality; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D009664:Norway / Q000453:epidemiology; D009293:Opioid-Related Disorders / Q000401:mortality / Q000534:rehabilitation*; D015995:Prevalence; D055815:Young Adult
D009292:Narcotic Antagonists; D002047:Buprenorphine; D008691:Methadone