Little is known about the excess mortality associated with use of some illicit substances. In particular, this concerns the risks associated with injection drug use and psychiatric disorders.

This study estimated mortality following substance abuse treatment among primary users of cannabis, cocaine, amphetamine, MDMA, and opioids. The risks associated with injection drug use and psychiatric comorbidity were assessed.

A register of individuals in treatment for illicit substance disorders was linked with registers on psychiatric treatment and mortality. The study population consisted of 20581 individuals who received treatment in Denmark between 1996 and 2006. There were 1441 deaths recorded over 111445 person-years of follow-up.

Standardized Mortality Ratios (SMRs) for primary users of specific substances were: Cannabis: 4.9, cocaine: 6.4, amphetamine: 6.0, heroin: 9.1, and other opioids 7.7. For MDMA the crude mortality rate was 1.75/1000 person-years, and the SMR was not significantly elevated. Sharing of syringes was associated with increased mortality in both primary users of opioids (hazard ratio (HR): 1.58 [95% CI 1.22–1.99], p < .001) and cocaine/amphetamine (HR: 9.52 (95% CI 3.94–23.02, p < .001). Overall, psychiatric comorbidity was associated with modestly increased mortality (HR: 1.15 [95% CI 1.03–1.29], p = .012) and in particular for primary users of cocaine/amphetamine (HR: 2.74 [95% CI 1.56–4.80], p < .001).

High SMRs were found among individuals who had received treatment for cannabis, cocaine, amphetamine, and opioid use disorders. Injection drug use was clearly associated with excess mortality, while the impact of psychiatric comorbidity was generally modest.