Risk of amphetamine use disorder and mortality among incident users of prescribed stimulant medications in the Veterans Administration

Background and aims: Non-medical use of prescribed stimulant medications is a growing concern. This study's aims were to ascertain the demographics of stimulant medication users compared with non-users, examine temporal trends of stimulant medication use and estimate risk factors for development of amphetamine use disorder (AUD) and mortality among new users of stimulant medications. Design: Cox proportional hazards regression in a retrospective cohort adjusted by baseline covariates. Setting: United States, national administrative database of the Veterans Affairs (VA) health-care system. Participants: Adult incident users of stimulant medications (n = 78 829) from fiscal years (FY) 2001 to 2012. Measurements: Primary outcomes were time-to-event: (1) occurrence of AUD diagnosis and (2) death. Baseline covariates included demographic information, Food and Drug Administration (FDA)-approved indications for stimulant use, substance use disorders (SUD) and depression. Findings: Stimulant users compared with non-users were younger, more likely to be non-Hispanic white and female. Incident stimulant medication users increased threefold from FY2001–FY2012 and eightfold among adults aged 18–44 years. Nearly one in 10 incident users in FY2012 had a comorbid baseline SUD. Off-label use was common—nearly three of every five incident users in FY2012. Comorbid SUDs among incident stimulant medication users were risk factors for occurrence of AUD during follow-up, with adjusted hazard ratio (AHR) estimates ranging from 1.54 to 2.83 (Ps < 0.05). Increased mortality risk was observed with occurrence of AUD during follow-up [AHR = 1.55, 95% confidence interval (CI) = 1.13–2.14, P = 0.007], while on-label prescribing was protective against death (AHR = 0.686, 95% CI = 0.63–0.75, P < 0.0001). Conclusions: In a US national cohort of adult incident stimulant medication users in the Veterans Affairs health-care system, measured from fiscal years 2001 to 2012, comorbid substance use disorders were common and were risk factors for development of an amphetamine use disorder (AUD). Increased mortality risk among incident users of stimulant medications was observed among both those who developed an AUD later and those whose use was defined as off-label.