Methadone-related deaths: a worrying increase

Objectives. Methadone has been used in Italy in maintenance programs for heroin addicts since the early 1980s. Its use requires a careful evaluation of the dosage, in relation with the opioid tolerance developed by the patient under treatment. The number of methadone-related deaths observed by our Laboratory has been increasing during the last five years: the aim of this work is to discuss the causes of such an increment, whether there has been an increase in methadone use without medical prescription, an incorrect use of the drug when take-home doses were prescribed, simultaneous consumption of alcohol or drugs, or even doctor’s carelessness at the Addiction Units when judging the appropriate methadone dosage. Materials and Methods. Between 2006 and 2010 we observed twenty cases of lethal poisoning related to methadone administration, seven of those in the year 2010 alone. Fifteen were males and five females, the average age being 32 (min 2 - max 54). The following toxicological analyses were carried out on postmortem samples: HS-GC quantitative analysis of ethanol in blood; GC-MS systematic toxicological analysis (STA) in blood followed by quantitative determination of identified drugs; GC-NPD determination of methadone in blood and in urine when available. Whenever possible (12 cases) GC-MS quantitative determination of methadone and morphine in hair (2 cm closest to the scalp) was performed. Results. It has been established that half of the deaths had been caused by methadone only, while in the other ten there had been contribution, besides methadone, of other substances (especially ethanol). The evaluation of the anamnestic data has allowed to observe that six of the deceased subjects were not following any methadone therapy, five had take-home methadone doses, while three other subjects had started methadone therapy just a few days earlier. In three of the remaining six cases, all involving subjects with supervised methadone consumption, blood alcohol concentration was over 200 mg/100 ml, and in one case there were high concentrations of Promethazine and Levomepromazine, the only medications found besides methadone. Highest blood methadone average concentrations (891 ng/ml) were surprisingly those related to subjects who had just started methadone treatment, followed by those of subjects with take-home doses (720 ng/ml). Lowest concentrations (455 ng/ml) were, conversely, those of subjects who had taken methadone without a doctor’s prescription and those of patients with supervised consumption by a drug treatment service (695 ng/ml). Conclusion. By evaluating the results we came to the following conclusions: 1) the death of three patients during induction into methadone treatment have been caused by administration of excessive starting doses; 2) when take-home doses are prescribed, sometimes patients display a tendency to irregular assumption of the drug, this being documented through the occasional findings of unconsumed syrup bottles at the patient’s domicile and through hair analysis, subsequently increasing the risk of overdosing; 3) in one single case, take-home methadone has indirectly lead to the death of a two years old girl who has drunk the syrup left unattended by her father; 4) among subjects with supervised consumption, high blood concentrations have generally not been observed, but there has been simultaneous alcohol or psychotropic drugs intake; 5) the abuse of methadone illegally obtained, often through patients allowed to carry it home, is rather common. Special caution has to be exercised in prescribing take-home doses, together with a more careful evaluation during induction into methadone treatment when tolerance is unclear. Key Words: Methadone, intoxication, blood levels