The role of concomitant drugs in the aetiology of fatal heroin- and methadone- related overdose

Heroin and methadone poisoning are significant causes of death of young people in the United Kingdom. In a high proportion of these fatalities concomitant substances are also detected. This thesis is concerned with the significance of this observation and the hypothesis that these substances are risk factors for fatal heroin- and methadone-related overdose. A referential database was developed incorporating post-mortem toxicology data from 1,222 heroin and methadone overdose fatalities from around England and Wales. The most commonly detected concomitant drugs were ethanol, diazepam, temazepam, an additional opioid and cocaine. In the first of two studies, statistical models were derived, using multiple linear regression, to assess the potential effect of these concomitant substances on the lethality of heroin and methadone. Log-log and semi-log models were considered and regression coefficients were estimated by ordinary least squares. Ethanol blood concentrations were associated with significantly reduced blood levels of total morphine and methadone, consistent with a causal role for this substance. There was an absence of evidence of a similar effect for other commonly detected concomitants.