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

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.