摘要：Objectives. We investigated whether nonmedical opioid pain reliever use is associated with higher mortality in the general US population. Methods. We assessed the history of nonmedical opioid pain reliever use among 9985 people interviewed at baseline of the Epidemiologic Catchment Area Program initiated in 1981 to 1983 in Baltimore, Maryland; St. Louis, Missouri; and Durham, North Carolina. We linked the data with the National Death Index through 2007. Results. Nonmedical opioid pain reliever use was 1.4%. Compared with no nonmedical drug use, mortality was increased for nonmedical opioid pain reliever use (hazard ratio [HR] = 1.60; 95% confidence interval [CI] = 1.01, 2.53) or nonmedical use of other drugs (HR = 1.31; 95% CI = 1.07, 1.62). Mortality was also higher for males and for those beginning nonmedical opioid pain reliever use before aged 15 years. Conclusions. A history of nonmedical opioid pain reliever use was associated with increased mortality, in particular for males and early onset users. The nonmedical use of opioid pain relievers is a major problem in the United States. The 2013 National Survey on Drug Use and Health indicated that 4.5 million people (or 1.7%) aged 12 years and older report recent use of these medicines outside the boundaries of prescribed use, and an estimated 350 000 persons aged 12 years and older recently initiated nonmedical use of pain relievers. 1 In that study, nonmedical use was defined as use without a prescription of one’s own or for the experience or feeling the drugs caused, which did not include the use of over-the-counter drugs or the legitimate use of prescription drugs. 1 Nonmedical use of opioid pain relievers has been linked to a variety of adverse health outcomes, 2,3 and elevated mortality rates have been observed consistently in previous studies, most often with treatment-seeking or -attending samples of drug users. 4,5 Several factors are believed to contribute to the higher mortality rates, 4 including the toxicity of the drug itself 6 ; various infections introduced by nonsterile injections such as HIV, hepatitis C, and wound-related infections 7 ; and other environmental factors associated with the use of opioids, such as greater exposure to violence and traumatic injuries. 8 Meta-analyses on mortality associated with the regular illegal use of opioids (including both the use of heroin and the nonmedical use of opioid pain relievers) were conducted in 1998 and 2010, which drew largely on users ascertained in treatment settings and not in general population settings. 4,5 On the basis of the results from 12 studies conducted in Europe and the United States from 1968 to 1991, Hulse et al. derived a pooled estimated mortality rate of 8.6 per 1000 person-years among heroin or nonmedical opioid pain reliever users, which was 13.2 times higher than was the mortality rate among nonusers. 4 Degenhardt et al. reviewed 58 prospective studies conducted globally from 1993 to 2008 5 ; they derived a pooled mortality rate of 20.9 per 1000 person-years for individuals with serious opioid involvement and reported a similar standardized mortality rate (SMR) of 14.7. Although the pooled mortality rates provide important descriptive epidemiological information on the relationship between opioid use and death, generalizability from these studies remains somewhat uncertain because of variations in study designs, sample sizes, and sampling methods (often convenience samples); short follow-up periods; and heterogeneity across the studies. Most studies on mortality and the use of opioids have been grounded on samples drawn from treatment centers or other services or from convenience samples, which may introduce selection biases because only a small fraction of opioid users ever receives treatment. 1 We built on research that has linked the history of mental and behavioral disorders with all-cause mortality 9 and in which drug use disorders were associated with markedly increased mortality. Although the use of opioid pain relievers and heroin is frequently linked with epidemics, studies have suggested that the epidemiology of opioid pain reliever use may not be synonymous with the epidemiology of heroin use. 10,11 However, our review of the literature disclosed no population-based studies on all-cause mortality risk and nonmedical use of opioid pain relievers. Because of the various adverse health outcomes associated with the nonmedical use of opioid pain relievers, 2,3 we hypothesized that people who used opioid pain relievers nonmedically would have higher mortality risks than would those who used drugs other than opioid pain relievers nonmedically and those who use no drugs at all. In addition, we hypothesized that nonmedical opioid pain reliever users with early age of onset or a history of daily or near-daily use would have a higher mortality rate than would those with older age of onset and no history of daily or near-daily use because they are more likely to have higher cumulative exposure to the drugs. To achieve these aims, we analyzed data from the Epidemiologic Catchment Area (ECA) study with a 27-year follow-up to investigate the mortality associated with a history of nonmedical use of opioid pain relievers. Probability sampling methods used in the ECA program gave us a representative sample of household-residing populations in these areas and made it possible to constrain the limitations of previous studies on the basis of clinical and convenience samples.
