Background: Prescription pain reliever use to get ‘high’ or outside the boundaries of the prescriber’s intent (extra-medical use) has become a major public health concern over the past twenty years in the United States (US). In recent years prevalence has stabilized, but the US has seen increases in opioid dependence, overdoses, and related deaths. Extra-medical prescription pain reliever (EMPPR) use often starts in adolescence, a pivotal stage of development. Each of this dissertation’s three aims address a series of research questions related to adolescent-onset use, dependence, and persistence of EMPPR use among newly incident adolescent users. The first aim is to estimate peak ages of becoming a newly incident EMPPR user and a subsequent opioid dependence case among adolescents. The second aim explores alcohol involvement as might affect whether adolescents belong to one of two classes of EMPPR use: susceptible-to-persistence (STP) or not-susceptible-to-persistence (NSTP), and estimates alcohol effects on the rate of EMPPR use for adolescents susceptible-to-persistent EMPPR use. The third aim investigates latent subgroups of newly incident EMPPR-using adolescents based on alcohol and EMPPR use patterns. Methods: Study populations are US community-dwelling adolescents 12-21 years old, with nationally representative samples for recent National Surveys on Drug Use and Health (NSDUH). For all three aims, EMPPR use, alcohol dependence, and opioid dependence were assessed via standardized, self-reported measures. The first study uses meta-analyses for independent replication samples from NSDUH 2002-2013 for summary risk estimates of developing opioid dependence by survey year and age pair. The second study applies the zero-inflated Poisson (ZIP) approach to estimate associations of underage drinking with persistence of EMPPR use for survey years 2002-2012 among 12-20 year olds. The final study employs latent class analysis (LCA) to distinguish subgroups of adolescent-onset newly incident EMPPR users in relation to characteristics of alcohol involvement and EMPPR use. Results: In US adolescents, the peak risk for transitioning from onset of EMPPR use to opioid dependence within 12 months is found at 14-15 years old [95% confidence interval (CI) = 6.3%, 8.7% per year], which is younger than the within-adolescence peak risk for starting EMPPR use (16-19 years old ; 95% CI = 4.1%, 5.9% per year). ZIP regressions showed that underage drinkers with alcohol dependence were more likely to be STP with an excess rate of EMPPR use (e.g., risk ratio: 1.3; 95% CI: 1.1, 1.5). Ancillary findings include associations with other levels of alcohol involvement, with shorter time since EMPPR initiation. A female excess rate of EMPPR use among the most recent initiates within the STP class is seen. Latent Class Analyses discovered three classes of newly incident users differentiated by facets of EMPPR and alcohol use: (1) Nondependent/Low level users, (2) Moderately persistent users, and (3) Persistent/Dependent users. Persistent/Dependent users were more likely to be female and younger when compared to the Nondependent/Low level class. Conclusions: Findings from this dissertation research shed light on newly incident EMPPR use among adolescents with further identification of vulnerabilities when alcohol and dependence syndromes manifest. These results provide insights that unveil the critical time for prevention efforts focused on reducing the incidence of EMPPR use and suggest intervention strategies aimed at preventing persistence of EMPPR use and development of opioid dependence.
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