A Global Perspective on Incidence and Regional Trends of Opioid Use Disorders From 1990 to 2021
Article information
Abstract
Objective
Opioid use disorders (OUDs) have become a significant global public health challenge. Despite extensive research on the opioid crisis, the trends in incidence and regional disparities remain inadequately understood.
Methods
Data were obtained from the Global Burden of Disease 2021, covering 204 countries and territories. OUDs incidence cases and rates per 100,000 population were analyzed over the study period. Trends were evaluated using the estimated annual percentage change (EAPC).
Results
Globally, OUDs cases increased by 49.25% from 1,301,551 (95% uncertainty interval [UI]: 1,077,634 to 1,598,053) in 1990 to 1,942,525 (95% UI: 1,643,342 to 2,328,363) in 2021. The incidence rate in 2021 was 24.62 per 100,000 population, with an EAPC of -0.25 (95% confidence interval: -0.39 to -0.1). Males had slightly higher rates than females (25.39 vs. 23.84 per 100,000). Individuals aged 15–49 years carried the highest burden, while older age groups showed the largest increases in cases. High-income North America reported the highest incidence rate in 2021 (123.28 per 100,000) and the largest case increase (425.34%). Among countries, the United States had the highest incidence rate increase (EAPC: 5.55), while Switzerland experienced the largest decline (EAPC: -4.33). A moderate positive correlation was identified between 2021 incidence rates and socio-demographic development (ρ=0.382, p<0.001).
Conclusion
This study highlights substantial global variability in OUDs trends, with significant differences across regions, sexes, age groups, and countries. Findings emphasize the need for tailored prevention and treatment strategies.
INTRODUCTION
Opioid use disorders (OUDs) have become one of the most challenging public health issues of the modern era, with profound impacts on individuals, families, and healthcare systems [1]. Despite significant advances in understanding the dynamics of the opioid crisis, the nature and scope of the epidemic continue to evolve, with shifting patterns of opioid misuse and varying regional responses [2]. As a result, there is a pressing need for continued research into the incidence and regional trends of OUDs to inform more effective prevention, treatment, and policy strategies [3].
Recent studies have documented the significant role of both prescription and illicit opioids in the progression of OUDs [4]. Research has highlighted how aggressive marketing and overprescribing in the late 20th and early 21st centuries contributed to the widespread misuse of prescription opioids [5]. As a response, many countries have implemented stricter opioid prescribing guidelines, which have led to a decrease in prescription opioid misuse in some regions [5,6]. However, this shift has often been accompanied by increased use of illicit opioids, particularly heroin and synthetic opioids like fentanyl, posing new challenges in regions with strict prescribing regulations [7].
Given the dynamic and multifactorial nature of the opioid epidemic, this study is crucial for gaining a deeper understanding of the global trends in OUDs and the regional factors that influence them. Therefore, this article provides a comprehensive investigation and analysis of the incidence of OUDs from 1990 to 2021, reviewing the potential influencing factors of global epidemiological trends through a retrospective analysis of large-scale epidemiological data from this period.
METHODS
Data collection and sources
This study utilized data from the Global Burden of Disease (GBD) 2021, which was accessed through the Global Health Data Exchange Query Tool [8]. The GBD 2021 dataset includes comprehensive information from 204 countries and 21 regions, covering the period from 1990 to 2021 [9]. These 21 regional groupings were selected based on geographical proximity and shared epidemiological features [8,9]. The data were categorized by year, sex, and age group, allowing for an in-depth examination of trends in OUDs incidence across various demographic groups. In addition, countries and regions were classified by their Socio-Demographic Index (SDI) into low, middle, and high SDI categories. This classification helped explore the relationship between socio-economic development levels and the prevalence of OUDs [10].
Disease definition
OUDs are defined as a maladaptive pattern of opioid use leading to clinically significant impairment or distress, including symptoms of dependence such as tolerance and withdrawal [7]. OUDs are a substance-related disorder characterized by dysfunctional opioid use patterns [3]. Cases included in the study must meet the diagnostic criteria for opioid dependence as defined by either the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) (code: 304.00) or the ICD-10 (code: F11.2), with the exclusion of cases where opioid dependence is due to a general medical condition [11]. According to DSM-IV-TR, a diagnosis of opioid dependence requires at least three of the following symptoms within a 12-month period [12,13]: tolerance (need for increased amounts or diminished effect with continued use), withdrawal (symptoms or use of similar substances to avoid withdrawal), using progressively larger amounts or for longer periods than intended, unsuccessful efforts to reduce use, excessive time spent obtaining the substance; giving up important activities due to use, and continued use despite physical or psychological problems caused by it [14].
Statistical analysis
This study aimed to assess the global burden of OUDs across various regions and countries from 1990 to 2021, incorporating a 95% uncertainty interval (UI) for each parameter. Incidence rates, standardized per 100,000 population, were used as the basis for analysis, while estimated annual percentage changes (EAPC) were calculated to examine trends over time [15]. A joint regression model was employed to assess the disease burden, with the EAPC derived using a logarithmic linear regression approach. Detailed calculations for the EAPC are provided in previous studies [16,17]. An increase in burden was indicated when the lower limit of the EAPC and its 95% confidence interval (CI) exceeded zero, while a decrease was indicated when the upper limit and 95% CI fell below zero. The EAPC was calculated using the formula [16]:
y=α+βx+ε: EAPC=(eβ-1)×100%.
Pearson correlation analysis was performed to explore the relationship between the EAPC and OUDs incidence rates. Correlation coefficients (ρ) and p-values were used to assess the strength and significance of these associations.
Ethical approval
This study was approved by the Fuzhou University Affiliated Provincial Hospital in line with the Declaration of Helsinki (approval ref: 20241101). As a result of the secondary data analysis in this study, the review board waived informed consent. Additionally, this article does not contain any personal information about patients. All authors are in agreement with the manuscript.
RESULTS
Global patterns in OUDs
Globally, the incidence of OUDs showed a significant increase in the number of cases from 1990 to 2021, rising from 1,301,551 (95% UI: 1,077,634 to 1,598,053) in 1990 to 1,942,525 (95% UI: 1,643,342 to 2,328,363) in 2021, representing a 49.25% increase. However, the incidence rate remained relatively stable during this period, with a slight decline from 24.4 (95% UI: 20.2 to 29.96) per 100,000 population in 1990 to 24.62 (95% UI: 20.82 to 29.51) per 100,000 population in 2021, as indicated by an EAPC of -0.25 (95% CI: -0.39 to -0.1) (Table 1).
Global incidence rates and trends of opioid use disorders by sex, age, SDI regions, and geographic location from 1990 to 2021
Sex-specific trends showed that while both males and females experienced increases in the number of cases, the EAPC for the incidence rate showed minor declines for males (-0.25, 95% CI: -0.46 to -0.05) and females (-0.23, 95% CI: -0.35 to -0.12). In 2021, males had slightly higher incidence rates at 25.39 (95% UI: 21.62 to 30.07) per 100,000 population compared to females at 23.84 (95% UI: 20.06 to 28.9) per 100,000 population (Figure 1A, B and Table 1). These findings underline the persistent burden of OUDs globally, with EAPC analyses revealing consistent trends across sexes, highlighting the need for continued focus on effective prevention and intervention strategies.
Global burden of opioid use disorders. A: Number of opioid use disorder cases by sex from 1990 to 2021. B: Incidence rates of opioid use disorders by sex from 1990 to 2021. C: Total number of opioid use disorder cases across various age groups from 1990 to 2021. D: Incidence rates of opioid use disorders across different age categories from 1990 to 2021.
Age-group variations in OUDs
Age-specific analysis revealed notable differences in the trends of OUD incidence across age groups [18]. The highest burden was consistently observed among individuals aged 15–49 years, with the number of cases increasing from 1,177,122 (95% UI: 947,146 to 1,464,831) in 1990 to 1,722,800 (95% UI: 1,431,425 to 2,092,539) in 2021, although the incidence rate remained relatively stable during the study period, as indicated by an EAPC of -0.29 (95% CI: -0.45 to -0.13). In contrast, individuals aged 50–74 years saw a substantial 71.34% increase in the number of cases (95% CI: 63 to 80), accompanied by a decline in the incidence rate (EAPC: -0.84, 95% CI: -0.9 to -0.79). The most pronounced growth was observed in the 75+ years age group, where the number of cases rose by 122.88% (95% CI: 104 to 149), despite a concurrent decline in the incidence rate, as reflected by an EAPC of -0.64 (95% CI: -0.74 to -0.53) (Figure 1C, D and Table 1). These findings emphasize the persistent high burden of OUDs among individuals aged 15–49 years, while also drawing attention to the growing absolute number of cases in older age groups.
Regional variability in OUDs
From 1990 to 2021, the number of cases increased most significantly in the high SDI and low SDI regions. In high SDI regions, cases rose from 207,664 (95% UI: 173,326 to 252,999) in 1990 to 609,681 (95% UI: 518,566 to 721,842) in 2021, reflecting a 193.59% increase and accompanied by an EAPC of 2.97 (95% CI: 2.63 to 3.3). Similarly, low SDI regions experienced substantial growth, with cases rising from 60,715 (95% UI: 48,592 to 77,001) in 1990 to 155,170 (95% UI: 124,663 to 194,320) in 2021, representing a 155.57% increase. In terms of incidence rates, high SDI regions had the highest incidence in 2021 at 55.73 per 100,000 population (95% UI: 47.4 to 65.98). In contrast, high-middle and middle SDI regions exhibited declines over the study period, with EAPCs of -1.68 (95% CI: -2.14 to -1.22) and -1.33 (95% CI: -1.48 to -1.18), respectively (Figure 2A, B and Table 1).
Trends in opioid use disorder incidence by region. A: New cases of opioid use disorder in different SDI regions from 1990 to 2021. B: Incidence rates of opioid use disorders in various SDI regions from 1990 to 2021. C: Incidence rates of opioid use disorders in 2021 by sex, globally, and within SDI regions and geographical areas. SDI, Socio-Demographic Index.
Geographically, significant variability was observed, with regions like high-income North America and Eastern Europe reporting the highest incidence rates in 2021. High-income North America had the highest global incidence rate at 123.28 (95% UI: 103.38 to 148.55) per 100,000 population, reflecting the most substantial regional burden, alongside a remarkable increase in cases by 425.34% (95% CI: 370 to 488). Similarly, Eastern Europe exhibited a high incidence rate of 62.48 (95% UI: 53.28 to 74.26) per 100,000 population, although this region experienced a decline in cases over time, with an EAPC of -0.85 (95% CI: -1.67 to -0.01). In contrast, East Asia recorded the sharpest reduction in incidence rates, declining from 34.49 (95% UI: 28.59 to 42.34) per 100,000 in 1990 to 16.64 (95% UI: 13.78 to 19.93) in 2021, with an EAPC of -3.02 (95% CI: -3.29 to -2.76) (Figure 2C and Table 1). Notably, males consistently exhibited higher incidence rates of OUDs compared to females across all SDI regions and geographic locations in 2021 (Figure 2C). High SDI and low SDI regions both demonstrated a growing number of cases, albeit with differing trends in incidence rates, while regions like high-income North America and Eastern Europe continue to bear disproportionately high burdens.
Country-specific differences in OUDs
From 1990 to 2021, countries exhibited notable variability in the trends of OUDs, reflected in changes in the number of cases, incidence rates, and EAPC values. The United States and Yemen experienced the largest increases in case numbers, with the United States rising by 472.25% (95% CI: 408.32 to 551.68) from 76,035.22 (95% UI: 62,125.89 to 95,104.29) in 1990 to 435,113.45 (95% UI: 362,566.92 to 528,377.7) in 2021, and Yemen increasing by 233.45% (95% CI: 189.66 to 274.92). In contrast, Switzerland and Italy demonstrated the most significant reductions, with Switzerland’s cases dropping by 60.48% (95% CI: -66.52 to -53.59) and Italy’s by 54.9% (95% CI: -60.22 to -48.51) (Figure 3A and Supplementary Table 1).
Geographic distribution of opioid use disorder incidence across 204 countries. A: Percentage change in the number of opioid use disorder cases between 1990 and 2021. B: Opioid use disorder incidence rates by country in 2021.
Incidence rates also varied widely across countries. The United States and Estonia reported the highest incidence rates in 2021, at 130.8 (95% UI: 109 to 158.84) and 118.5 (95% UI: 99.8 to 138.43) per 100,000 population, respectively, highlighting significant public health burdens. In contrast, Cook Islands and Tokelau recorded the lowest incidence rates, at 12.95 (95% UI: 10.68 to 15.75) and 13.79 (95% UI: 11.39 to 16.6) per 100,000 population, respectively (Figure 3B and Supplementary Table 1). In terms of trends, the United States and Sweden exhibited the fastest increases in incidence rates, with EAPCs of 5.55 (95% CI: 4.99 to 6.12) and 4.55 (95% CI: 4.32 to 4.78), respectively. On the other hand, Switzerland and Italy experienced notable declines, with EAPCs of -4.33 (95% CI: -4.69 to -3.96) and -3.43 (95% CI: -3.69 to -3.17), respectively (Supplementary Table 1). These disparities underscore the heterogeneous burden and dynamics of OUDs across countries.
Analysis of correlations in OUDs trends
The analysis of correlations in OUDs trends revealed notable patterns linking historical incidence rates, socio-demographic development, and disease burden. A weak but statistically significant negative correlation was found between EAPC and incidence rates in 1990 (ρ=-0.178, p=0.015), indicating that countries with higher baseline incidence rates in 1990 tended to experience slower growth or declines in incidence trends over time (Figure 4A). In contrast, there was no significant correlation observed between EAPC and the SDI in 2021 (ρ=-0.106, p=0.151), suggesting that socio-demographic factors alone may not fully explain changes in OUD incidence trends across countries (Figure 4B). However, a moderate positive correlation (ρ=0.382, p<0.001) was identified between incidence rates per 100,000 population and SDI in 2021, indicating that higher SDI levels were associated with higher OUD incidence rates (Figure 4C). This relationship highlights the disproportionate burden faced by countries with advanced socio-demographic development, such as the United States and Estonia, which exhibited significantly elevated incidence rates compared to other regions. These findings underscore the intricate interplay between historical burden, socio-demographic progress, and OUD trends, emphasizing the need for tailored interventions addressing both historical and current drivers of the disease.
Correlation between opioid use disorder incidence, EAPC, and SDI. A: Relationship between opioid use disorder incidence and EAPC in 1990. B: Link between the SDI and opioid use disorder incidence in 2021. C: Association between opioid use disorder incidence and SDI at the national level. SDI, Socio-Demographic Index; EAPC, estimated annual percentage change.
DISCUSSION
The findings of this study provide a comprehensive analysis of global trends, regional variability, and country-specific differences in OUDs from 1990 to 2021, offering valuable insights into the evolving nature of the opioid epidemic. The global increase in the number of OUDs cases, despite a relatively stable incidence rate, reflects the impact of population growth and underscores the need for more effective strategies to reduce the burden of OUDs. The slight decline in incidence rates, as evidenced by the negative EAPC values, suggests some progress in managing the epidemic in certain regions; however, these declines have not been sufficient to offset the overall rise in case numbers. This finding aligns with previous research documenting the resilience of the opioid crisis and its capacity to adapt to shifting socio-demographic and regulatory contexts [18-21].
The persistent high burden among individuals aged 15–49 years emphasizes the critical need for targeted prevention and intervention efforts aimed at younger and middle-aged populations, who are most affected by the epidemic [22]. This demographic trend is consistent with earlier studies highlighting the intersection of OUDs with employment instability, social stressors, and co-occurring mental health disorders. Moreover, the substantial rise in the number of cases among older populations (75+ years) reflects an emerging challenge likely driven by long-term prescription opioid use, chronic pain management, and age-related vulnerabilities to substance misuse. These findings echo recent research that has identified the aging population as a growing contributor to the global burden of OUDs, particularly in high-income settings [21,23].
Significant geographic variability in OUDs trends further underscores the multifaceted nature of the epidemic. High-income North America, which exhibited the highest incidence rates and the most substantial increase in case numbers, highlights the entrenched nature of the opioid crisis in this region, as documented extensively in prior studies [24,25]. The United States, in particular, has experienced successive waves of opioid misuse, driven by prescription opioids, heroin, and, more recently, synthetic opioids such as fentanyl [26,27]. In contrast, regions such as Eastern Europe demonstrated a high burden but declining trends in OUDs incidence, which may reflect the impact of harm reduction strategies, improved treatment accessibility, or shifts in opioid availability and use patterns. These regional disparities align with previous research that has emphasized the importance of localized public health responses in addressing the opioid crisis [28].
At the country level, the stark differences in OUDs trends further illustrate the heterogeneity of the epidemic. Countries such as the United States and Estonia recorded the highest incidence rates in 2021, reflecting the challenges of balancing access to pain management with the risks of opioid misuse [24]. Conversely, countries like Switzerland and Italy demonstrated significant declines in OUD cases and incidence rates, potentially indicative of successful public health interventions, stricter regulatory controls, and the integration of harm reduction measures into healthcare systems. Sex differences also contribute to these variations, with socio-economic factors and behavioral differences playing a significant role. For example, males tend to have higher rates of opioid misuse due to various factors, including greater risk-taking behaviors and socio-cultural expectations surrounding masculinity. These findings reinforce the importance of evidence-based policies tailored to specific national contexts, addressing both gender and regional disparities, as highlighted in previous studies [29].
While this study offers valuable insights into the global and regional dynamics of OUDs, it is important to acknowledge certain limitations [14]. The reliance on modeled estimates from the GBD 2021 introduces some uncertainty, and variations in data quality across countries may affect the precision of the findings [30]. Furthermore, the analysis does not account for specific policy interventions or cultural factors that may have influenced OUDs trends in individual countries [31]. Despite these limitations, this study provides a robust foundation for understanding the global burden of OUDs and offers critical guidance for the development of targeted and effective public health strategies.
In conclusion, the findings of this study underscore the complex and evolving nature of the opioid epidemic, highlighting the urgent need for coordinated global efforts to address the burden of OUDs. By understanding the factors driving OUDs trends and regional disparities, policymakers and public health officials can develop tailored interventions to mitigate the devastating impact of the opioid crisis on individuals, families, and societies worldwide.
Supplementary Materials
The Supplement is available with this article at https://doi.org/10.30773/pi.2025.0039.
Trends in the number of incidence cases and incidence rates of opioid use disorders in 204 countries from 1990 to 2021
Notes
Availability of Data and Material
The data are available from the Global Burden of Disease Results Tool of the Global Health Data Exchange (http://ghdx.healthdata.org/).
Conflicts of Interest
The authors have no potential conflicts of interest to disclose.
Author Contributions
Conceptualization: Tiantian Tuo, Yupeng Chen, Danyang Wang. Data curation: Jinna Liu. Formal analysis: Jinna Liu. Investigation: Yujiao Wu, Jiawen Wang. Methodology: Tiantian Tuo, Yupeng Chen. Project administration: Tiantian Tuo, Yupeng Chen. Writing—original draft: Yujiao Wu, Jiawen Wang. Writing—review & editing: all authors.
Funding Statement
None
Acknowledgments
We would like to acknowledge the long-standing efforts of the Global Burden of Disease collaboration team in providing the valuable data and resources that made this study possible.