Objectives Heroin users are at high risk of premature mortality. Despite the evidence supporting methadone maintenance programmes (MMT), methadone itself has been associated with drug-related deaths. This study aims to determine whether people prescribed methadone have an elevated risk of overdose mortality during periods of treatment transition, particularly during treatment initiation.
Method Retrospective cohort study of 3162 Scottish people prescribed and dispensed liquid methadone between January 1993 and February 2004. Observation time was defined as a period during methadone treatment or a period of maximum 6 months after leaving treatment. Individual observation time was censored after 6 months off-treatment. A person's observation time started again if they re-entered treatment after an off-treatment period. The main outcome measure was drug-related mortality by means of Cox-proportional hazards models during the 12 years of follow-up. Drug-related deaths occurring during treatment or within 3 days after last methadone prescription were considered as cases “on treatment”. Fatalities occurring 4 days or more after leaving treatment were considered to be drug-related deaths “off treatment”.
Results Overall 130 people died, with 51 deaths identified as drug-related deaths (20 off treatment and 31 in treatment). Risk of drug-related mortality was higher during treatment than off treatment (adjusted hazard ratio 11.17, 95% CI 4.51 to 27.64). Inspection of timing of death showed that the risk of drug-related mortality was higher during the initial two weeks of treatment (adjusted hazard ratio 16.93, 95% CI 5.17 to 55.46) compared to the risk of mortality off treatment. Similarly, retention in treatment for more than 3 weeks was associated with increased mortality relative to being off treatment (adjusted hazard ratio 9.97, 95% CI 4.08 to 24.39). In relation to risk of mortality during treatment, being in treatment for 3–10 weeks (adjusted hazard ratio 0.36, 95% CI 0.15 to 0.85) or greater than 10 weeks (adjusted hazard ratio 0.13, 95% CI 0.04 to 0.39) was associated with a reduced risk of mortality compared to the initial two weeks on treatment. These effects were observed after adjusting for all or some of the following covariates; co-prescribing of benzodiazepines, psychiatric admission, number of methadone treatments, overuse of methadone and urine testing, where appropriate.
Conclusion Excess mortality risk in the initial two weeks of methadone treatment indicates the need for more care in prescribing and monitoring of methadone when starting or restarting a patient on methadone maintenance therapy.
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