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Prospective Study of QTc Changes Among Former Opiate Addicts Since Admission to Methadone Maintenance Treatment: Benzodiazepine Risk

Peles, Einat PhD; Linzy, Shirley RN, MS; Kreek, Mary Jeanne MD; Adelson, Miriam MD

doi: 10.1097/ADM.0b013e3182a8a4f2
Original Research

Objectives: To prospectively evaluate QTc changes among methadone maintenance treatment (MMT) patients.

Methods: All 512 opiate addicts newly admitted to 2 MMT clinics had been prospectively studied for 4.5 years. Ninety-one patients were excluded because they were admitted from other MMTs, and 26 were excluded because their first electrocardiogram was performed following 28 days in MMT; therefore, 421 were studied. QTc values were again performed either after (A) a steady methadone dose for at least 3 months and negative urine tests for opiates, cocaine, amphetamines, cannabis, benzodiazepine; or after (B) same as for (A) but with positive urine tests for cannabis and/or benzodiazepine.

Results: Mean QTc intervals were not related to benzodiazepine or cocaine use on admission. QTc interval was significantly prolonged from the baseline to steady methadone dose (424.5 ± 23.2 ms and 438.6 ± 26.6 ms, respectively) but not affected by methadone dose (<100 or ≥100 mg/d) or by the time to achieve a steady methadone dose (between 3 months and >2 years). QTc prolongation was greater among patients whose urine tested positive for benzodiazepine on a steady dose (P = 0.003). No additional prolongation was observed in 49 patients who achieved a steady methadone dose less than 1 year in MMT and had additional follow-up. Two patients who were benzodiazepine abusers died for undefined reasons.

Conclusions: There is significant QTc prolongation during early MMT with no apparent clinical significance. A combination of benzodiazepine and methadone should be monitored.

From the Dr Miriam and Sheldon G. Adelson Clinics for Drug Abuse Treatment and Research (EP, MA), Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Dr Miriam and Sheldon G. Adelson Clinics for Drug Abuse Treatment and Research (SL, MA), Las Vegas, NV; Laboratory of the Biology of Addictive Diseases (MJK, MA), The Rockefeller University, New York, NY.

Send correspondence and reprint requests to Einat Peles, PhD, Adelson Clinic for Drug Abuse, Treatment and Research, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv 64239, Israel. E-mail address:

The study was funded by the Adelson Family Foundation.

The authors declare no conflicts of interest.

Received February 18, 2013

Accepted August 08, 2013

© 2013 American Society of Addiction Medicine