Abstract
BACKGROUND: The escalating global burden of opioid use disorder (OUD) necessitates a nuanced understanding of its epidemiological patterns, socioeconomic determinants, and temporal trends. This study quantifies the global, regional, and national burden of OUD-related mortality and disability, evaluates policy correlates, and identifies critical disparities across demographic and socioeconomic strata. METHODS: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017–2021, we analyzed age-standardized mortality rates (ASMRs), disability-adjusted life years (DALYs), and their 95% uncertainty intervals (UIs) across 204 countries and territories. Joinpoint regression modeled temporal trends, while multivariable generalized estimating equations (GEEs) assessed socioeconomic gradients via the Socio-demographic Index (SDI). Geospatial clustering was evaluated using Moran’s I statistic. Robustness was confirmed through sensitivity analyses, counterfactual modeling, and cross-validation. RESULTS: Globally, OUD mortality increased by 12.4% between 2017 and 2021, with the Americas remaining the epicenter (ASMR: 5.72 per 100,000; +47.3% deaths). Europe demonstrated progress (mortality decline: -1.8%), while Asia and Africa faced rising chronic disability (DALYs: +3.0% and + 10.2%, respectively). National-level extremes ranged from 0.01 per 100,000 in Japan to 7.16 per 100,000 in Canada. A pronounced socioeconomic gradient emerged: high-SDI regions exhibited 17.8-fold higher mortality rates (0.641% vs. 0.036% in low-SDI regions) and 13.9-fold greater DALY rates. Sex disparities persisted (male-to-female mortality ratio: 4.7:1), with males experiencing biphasic trends (+ 3.8% annual percent change [APC] pre-2020, -6.5% post-2020). Geospatial analyses revealed diverging trajectories, including rising mortality in the Americas (+ 4.2% APC) and declines in Africa (-3.1% APC). CONCLUSION: This study highlights stark regional and socioeconomic disparities in the OUD burden, exacerbated by synthetic opioid proliferation in high-income settings and chronic disability in resource-limited regions. Evidence-based harm reduction policies in high-SDI nations mitigated disability, while low-SDI regions faced accelerating crises. Targeted interventions addressing socioeconomic inequities, gender-specific risks, and geospatial vulnerabilities are urgently needed to curb the global opioid epidemic.