Biological stress is a natural defense mechanism that helped early humans respond to danger. Today, it remains a complex psychophysiological reaction to internal or external pressures, involving nearly every system in the body (APA Dictionary of Psychology; Gloaguen, 2017). While short-term stress can be adaptive, chronic stress weakens the immune system, increases the risk of physical and mental illness, and disrupts metabolic balance (Dhabhar, 2014; Chandola et al.,2006). Its long-term effects—ranging from cardiovascular issues to depression—contribute significantly to the global burden of disease. As chronic stress becomes a hallmark of modern life, its repercussions extend beyond health, placing growing pressure on healthcare systems and economies.

We will review in this article how we can study the economic impact of stress and the latest corpus of knowledge on the topic.

1.    Methodological Approaches to Estimating the Economic Impact of Stress

Estimating the economic impact of stress requires a multidimensional approach that accounts for both direct and indirect costs.

1.1.Study of direct costs

Direct costs typically encompass healthcare utilization—such as hospital admissions, general practitioner visits, specialist consultations, diagnostics, and medication usage.

A commonly used analytical framework is the Cost-of-Illness (COI) approach, which calculates the overall economic burden of a condition by aggregating healthcare costs and productivity losses. This can be implemented via a top-down approach (using aggregated national statistics and healthcare expenditures) or a bottom-up approach (using patient-level data and workforce metrics). Both methodologies must carefully attribute outcomes specifically to stress, which is often comorbid with other physical and mental disorders, potentially inflating or obscuring estimates (Tarricone, 2006; Hassard et al., 2018).

1.2.Study of indirect costs

Indirect costs refer to productivity-related losses, including absenteeism (missed workdays), presenteeism (reduced performance while at work), long-term disability, and premature exit from the workforce. For estimating indirect costs, two primary economic models are used:

1. The Human Capital Approach (HCA) assumes that each hour or day of work lost due to stress equates to a direct loss in productivity, usually monetized based on average wages or GDP per capita. This method is useful for measuring long-term losses, especially in chronic stress-related conditions (Kigozi et al., 2016).
2. The Friction Cost Approach (FCA) provides a more conservative estimate, focusing on the time it takes to restore productivity, either by reallocating tasks or replacing absent workers. While more aligned with real-world labor dynamics, FCA may underestimate the economic consequences of chronic stress or mental health issues (Koopmanschap et al., 1995).

To assess presenteeism and absenteeism, validated tools like the Work Productivity and Activity Impairment Questionnaire (WPAI) and the Health and WorkPerformance Questionnaire (HPQ) are employed. These instruments allow respondents to self-report time lost and reduced effectiveness at work due to health conditions, including stress. The HPQ, for instance, has been validated across multiple occupational settings and includes adjustments for potential self-reporting bias (Kessler et al., 2003).

Stress exposure itself is typically assessed using tools such as the Perceived StressScale (PSS) or the Job Content Questionnaire (JCQ), often in conjunction wit hadministrative data (e.g., payroll, sick leave, and disability claims) for enhanced robustness (Cohen et al., 1983; Karasek et al., 1998).

1.3.Statistical methods

Advanced statistical techniques, including longitudinal cohort designs, fixed-effects regression, and structural equation modeling (SEM), are employed to examine causal relationships over time and adjust for confounding variables (Goetzel etal., 2004). These methods allow for a more comprehensive understanding of how stress translates into economic costs at both individual and systemic levels.

1.4.Methodological challenges

Despite methodological advancements, challenges remain—especially regarding the attribution of outcomes specifically to stress, as well as the difficulty in quantifying intangible costs, such as reduced quality of life, care giver burden, or emotional strain.

Nevertheless,the integration of epidemiological, economic, and organizational data through multi-method approaches provides increasingly accurate estimates of stress’s profound impact on healthcare systems and labor productivity.

2.    Direct HealthcareExpenditures Attributable to Stress

According to Cigna’s care report 2019 on Global Well‑Being Survey projects that 4–19%of overall healthcare spending is stress-related, equating toUS$0.7–133 billion annually, with 25% of hospitalizations and 35% of emergency department visits linked to stress (Sadler, 2019).

Ciagna performed study assessed healthcare usage by patients with stress-related conditions in the UK, US, and Australia, focusing on inpatient admissions, outpatient visits, emergency care, and primary care. Data was primarily drawnfrom ICD-coded sources provided by national health agencies. To estimate theimpact of stress-related mental illness presenting as physical symptoms, we used peer-reviewed literature. Authors then applied these benchmarks to six other markets—Hong Kong, Taiwan, Singapore, South Korea, Thailand, and theUAE—to estimate direct healthcare costs. The reported analysis includes only costs directly linked to stress, it likely underrepresents the broader economic burden.

In addition to clearly defined clinical conditions directly linked to stress, there are numerous stress-associated mental health disorders that impose a significant, yet often underestimated, economic burden. Among them, major depressive disorder (MDD) and post traumatic stress disorder (PTSD)are particularly prominent. In 2019, an estimated 19.8 million adults in theUnited States were living with MDD, with a notable gender disparity (62.7%female) and a high rate of severity (32.9% classified as severe). The associated incremental societal economic burden of MDD was estimated at $333.7billion (equivalent to $382.4 billion in 2023 USD), translating to approximately $16,854 per affected individual. The primary cost components included healthcare expenditures ($127.3 billion; 38.1%),household-related costs ($80.1 billion; 24.0%), reduced productivity due to presenteeism ($43.3 billion; 13.0%), and absenteeism ($38.4 billion; 11.5%)(Greenberg et al., 2023). Simulation models suggest that the introduction of a novel therapy with a 50% early response rate could reduce this economic burden by 7.7% within a year, compared to standard care.

Similarly,PTSD represents a substantial financial challenge. In 2018, the excess cost attributed to PTSD in the U.S. was estimated at $232.2 billion, including $66 billion in direct healthcare costs alone (Davis et al.,2022). The total economic burden of PTSD not only reflects direct medical spending but also rivals that of other high-cost mental health conditions. As such, increased recognition, the development of more effective treatments, and broader implementation of evidence-based interventions are critical to alleviating both the clinical and economic impact of PTSD.

3.    Indirect Costs:Productivity Loss, Absenteeism, Presenteeism

Indirect costs linked to stress—especially those related to lost productivity—often surpass direct medical expenses, particularly among working-age adults. These costs emerge primarily through absenteeism (absence from work due to illness), presenteeism (reduced performance while at work despite illness), and premature exit from the workforce.

Absenteeism due to stress and stress-related mental health conditions, such as anxiety and depression, leads to measurable productivity loss. Epidemiological studies report that individuals with high perceived stress experience more frequent and longer sick leaves, increasing strain on both employers and public insurance systems (Hassard et al.,2017). In many European countries, stress-related sick leave constitutes a growing proportion of long-termabsences.

Presenteeism, though harder to quantify, often results in greater economic loss than absenteeism.Individuals who remain at work while mentally or physically impaired by stress demonstrate reduced output, increased errors, and slower recovery. Measurement tools like the Work Productivity and Activity Impairment Questionnaire (WPAI)show that stress-related presenteeism may account for over 60% of totalproductivity losses in some sectors (Goetzel et al., 2004). High job demands, low autonomy, and insufficient workplace support are key contributors to this phenomenon.

Chronic stress is also associated with early labor force withdrawal and long-term disability. Burnout and job strain significantly increase the risk of early retirement or unemployment, particularly in sectors like healthcare, where emotional demands are high (Ahola et al.,2009). The resulting loss of experienced personnel has downstream effects on system capacity, requiring increased recruitment and training expenditures.

On a macroeconomic scale, job stress is estimated to cost the U.S. economy over US$300 billion annually, with similar impacts projected globally (American Institute of Stress, 2022;WHO, 2016). These estimates include absenteeism, turnover, productivity loss, and healthcare spending. Notably, the burden is amplified in caregiving settings, where family members experience secondary stress and lost earnings, thoughthese are rarely included in national cost estimates.

Presenteeism and stress-related workforce attrition also affect healthcare providers themselves.Burnout among clinicians has been linked to lower care quality, higher errorrates, and increased intent to leave the profession, compounding the pressures on already fragile healthcare systems (West et al., 2018).

In sum, indirect costs of stress—particularly through lost productivity—are substantial and multifactorial. Addressing them requires not only improved access to mentalhealth care but also organizational interventions that reduce workplacestressors and foster resilience.

4.    Work-Related Stress

Psychosocialrisks at work refer to elements of jobdesign and work environment—such as low autonomy, poor leadership, and unfair treatment—that can negatively affect mental and physical health (Cox et al.,2000). These factors have been linked to depression, substance abuse, heart disease, reduced job performance, and even premature death (Bonde, 2008; Kivimäki et al., 2002). Despite growing awareness, such risks remain widespread in today’s workplaces (Leka & Jain, 2010).

Understandingthe economic impact of work-related stress is increasingly recognized asessential in public and occupational health. Cost-of-illness (COI) studiesprovide estimates of the total financial burden borne by individuals,employers, and society (Tarricone, 2006). However, their methods and findingsare not always well understood by researchers, which can limit theirusefulness. The following sections outline the key concepts and methods behind these studies.

• A meta-analysis estimated that 70–90% of costs from work-related stress derive from production losses, while 10–30% are healthcare expenditure (Hassard et al., 2017).
• In the U.S., job-related stress costs exceed US$300 billion/year, mainly via absenteeism, turnover, and diminished performance (UML‑Total Worker Health, 2020).
• Stanford estimates link workplace stress to US$190 billion in U.S. healthcare expenses, plus global productivity losses reaching US$1 trillion; burnout alone contributes US$322 billion in turnover- and productivity-related costs (Wonder, 2021).

5.  Integrating Economic and Healthcare System Resilience

The dual burden of stress-related direct healthcare costs and productivity losses increases demandand inefficiencies in already strained systems (Sadler, 2020)

Improving cost-awareness among providers—such as in the context of DRG systems—could mitigate inefficiencies exacerbated by stress (Lüdemann et al., 2024). Likewise, preventing stress-related illness (e.g. via workplace interventions or mental health services) has potential to reduce system-wide burden.

6.  Policy and Practice Recommendations

1. Adopt Broad Cost-of-Illness Frameworks
       Incorporate direct, indirect, and intangible costs—including mental, somatic, social, and productivity dimensions.
2. Standardize Definitions and Measurement
       Align on stress definitions (e.g., Perceived Stress Scale, job strain models) to improve data comparability.
3. Strengthen Provider Cost-Awareness
       Integrate economic literacy and utilization awareness into clinical training and clinical workflow to optimize resource use (Lüdemann et al., 2024)
4. Promote Preventive and Workplace Interventions
       Organizational policies and public health campaigns (e.g. stress-management programs) can curb both personal and system-level costs (Sadler, 2020).
5. Target Equity and Access Gaps
       Mental-health inequities drive avoidable cost via overuse of emergency services—prioritize community-based access
6. Expand Research into LMIC Contexts
       Stress impacts and resource constraints differ globally—COI studies should extend to LMIC settings.

Conclusion

Stress exerts a multifaceted economic burden on healthcare systems. While direct medical costs are substantial, indirect impacts—productivity losses, comorbidities, and provider inefficiencies—amplify system strain. The current literature, though significant, is limited by definitional heterogeneity, methodological bias toward high-income countries, and gaps in capturing intangible costs.Nonetheless, stress-related healthcare burdens are among the top expenditures facing modern systems. Coordinated public-health, workplace, and policy-level interventions—including cost-aware, preventive, and equity-focused strategies—offer considerable return on investment. As Apollo 2028explores future healthcare resilience, stress mitigation should be a strategic priority to safeguard both health and economic stability.

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