Risk Factors for Serious Prescription Opioid-Related Toxicity or Overdose among Veterans Health Administration Patients

TLDR

Prescription opioid use and related deaths have risen sharply since 1999, yet factors driving serious toxicity in medical users remain poorly understood. The study examined risk factors for serious opioid toxicity among VHA patients using a retrospective nested case‑control design. Researchers matched each of 817 cases to ten controls and applied logistic regression to identify predictors of toxicity. High daily morphine‑equivalent doses (≥100 mg), prior opioid dependence, recent hospitalization, liver disease, extended‑release opioids, and even lower doses (≥20 mg) were strongly linked to serious toxicity, suggesting that screening and naloxone coprescribing could reduce overdose risk.

Abstract

Prescription opioid use and deaths related to serious toxicity, including overdose, have increased dramatically in the United States since 1999. However, factors associated with serious opioid-related respiratory or central nervous system (CNS) depression or overdose in medical users are not well characterized. The objective of this study was to examine the factors associated with serious toxicity in medical users of prescription opioids.Retrospective, nested, case-control analysis of Veterans Health Administration (VHA) medical, pharmacy, and health care resource utilization administrative data.Patients dispensed an opioid by VHA between October 1, 2010 and September 30, 2012 (N=8,987).Cases (N=817) experienced life-threatening opioid-related respiratory/CNS depression or overdose. Ten controls were randomly assigned to each case (N=8,170). Logistic regression was used to examine associations with the outcome.The strongest associations were maximum prescribed daily morphine equivalent dose (MED)≥ 100 mg (odds ratio [OR]=4.1, 95% confidence interval [CI], 2.6-6.5), history of opioid dependence (OR=3.9, 95% CI, 2.6-5.8), and hospitalization during the 6 months before the serious toxicity or overdose event (OR=2.9, 95% CI, 2.3-3.6). Liver disease, extended-release or long-acting opioids, and daily MED of 20 mg or more were also significantly associated.Substantial risk for serious opioid-related toxicity and overdose exists at even relatively low maximum prescribed daily MED, especially in patients already vulnerable due to underlying demographic factors, comorbid conditions, and concomitant use of CNS depressant medications or substances. Screening patients for risk, providing education, and coprescribing naloxone for those at elevated risk may be effective at reducing serious opioid-related respiratory/CNS depression and overdose in medical users of prescription opioids.