Overdose mortality is the major adverse health effect of drug injection. The potential determinants of overdose death are poorly understood; the aim of this study was to investigate risk factors for overdose mortality among intravenous drug users (IVDU). A cohort of 4200 IVDU attending methadone treatment centres in Rome during the period 1980–1988, was enrolled. Data were collected from clinical records. Vital status and cause of death were ascertained as of 31 December 1988. A matched case-control analysis within the cohort was performed to identify risk factors of death from overdose. All overdose deaths wore included as cases and four controls, matched on year of birth and sex, were selected for each case from among the cohort members still alive at the time of death of the corresponding case. In all, 81 deaths from overdose were identified as cases and compared with 324 controls. A high risk of overdose death occurred among subjects who left treatment compared with those still in treatment (odds ratio (OR]=3.55, 95% confidence interval [CI]; 1.82–6.90). The OR was particularly elevated in the first 12 months after drop-out compared with those retained in treatment (OR=7.98, 95% CI: 3.40–18.73). The risk of overdose death was higher for unmarried compared with married people (OR=2.48, 95% CI: 1.31–4.68); a higher risk of overdose death was also associated with lower educational status and younger age at first drug use, but such association was not statistically significant. Methods to predict drop-out, in order to increase retention in treatment, and strategies to maintain contact with drop outs are warranted to decrease overdose mortality.

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