Introduction
Major depressive disorder (MDD) is an episodic and recurrent condition that affects over 300 million people globally and is a leading cause of disability worldwide [
1,
2]. The impact of MDD on an individual’s daily functioning can be severe, which may in turn worsen depressive symptoms, creating a downward spiral in the ability to fulfill family, work, and social responsibilities [
2]. In the USA, MDD was shown to account for 2.7 million disability-adjusted life-years in 2016, representing the largest burden among all mental and behavioral health disorders [
3]. Managing and treating MDD is often challenging because of its highly comorbid nature with other mental and physical conditions, which can impact patient adherence to treatment [
4‐
7].
The economic burden of US adults with MDD has increased considerably over time, rising from $236 billion in 2010 to $326 billion in 2018 (2020 US dollars [USD]) [
8]. In recent estimates [
8], several cost components were incorporated to calculate the economic burden of MDD that were not part of earlier estimates, including healthcare costs, suicide-related costs, and workplace costs (i.e., absenteeism and presenteeism). While healthcare costs are traditionally considered core components in economic appraisals and value discussions for novel therapies, there has been growing recognition of the need to adopt a more holistic view of disease burden as proposed in the ISPOR value flower framework [
9,
10]. Consideration of a broader range of cost components may allow for a more comprehensive assessment of costs to evaluate the potential economic implications of a condition on the individual affected as well as on their family/caregivers and society at large. Previous research has demonstrated that the burden of MDD is multifaceted and extends beyond direct costs [
8], highlighting the importance of considering components such as productivity loss within as well as outside of the workplace (e.g., due to unemployment or premature mortality) when attempting to contextualize the societal impact of MDD. Furthermore, the spillover effect of the disease burden on families and households is not typically factored into economic and value estimates and is a cost component that has not yet been quantified in MDD to our knowledge [
9,
11].
Constructing an impact model of MDD with a broad societal perspective in a systematic way not only helps quantify the disease-level burden but can also serve as a tool to quantify the potential impact of external factors that can increase (such as the COVID-19 pandemic) or decrease (such as therapeutic innovation) the burden. The current study sought to provide an updated estimate of the incremental economic burden of MDD in the USA from a societal perspective by expanding on prior analyses [
8] and more comprehensively assessing the burden of MDD using up-to-date literature, refined methods, and incorporating several novel components (i.e., unemployment, all-cause mortality, and household-related costs). To illustrate the utility of such a model, the potential impact of a hypothetical therapy for MDD that is more effective and acts more rapidly than the current standard of care on the incremental economic burden of MDD was also simulated. Variations of this simulation could help contextualize the benefit of therapeutic innovations on the societal burden of MDD and provide unique insights beyond those captured by traditional approaches to value assessments to help inform decision- and policymakers.
Discussion
The current study provides a comprehensive and updated assessment of the societal economic burden of adults with MDD as of 2019, with a simulation demonstrating the potential impact of a more effective, rapid-acting novel therapy for MDD. The total incremental costs associated with MDD in 2019 amounted to $333.7 billion (equivalent to $382.4 billion in 2023 USD), or $16,854 per adult with MDD, which was driven by indirect costs (61.9%), including work-related costs of adults with MDD (37.8%; presenteeism, 13.0%; absenteeism, 11.5%; unemployment, 9.1%; all-cause mortality, 2.9%; disability, 1.4%) and work-related costs of adults without MDD living in a household with an adult with MDD (24.0%). As a result of the heterogeneity in the data sources used to obtain the estimate of the economic burden of MDD, it is possible that some cost components were underestimated or overestimated. Therefore, the sensitivity analyses provide an important range of the economic burden of MDD during 2019 of $254.4 to $418.6 billion.
Almost two-thirds of the economic burden of MDD being attributed to indirect costs is consistent with previously published findings [
8] and highlights the importance of government agencies and employer groups in adopting strategies for managing MDD.
The current estimate of total incremental costs of MDD in 2019 represents a 3.5% increase in the burden compared with a prior estimate in 2018 (when standardized to 2019 values), with 36.0% of the total incremental costs of MDD in 2019 coming from novel components not previously included in the prior estimate (i.e., unemployment, all-cause mortality, household-related costs) [
8]. These costs likely increased in the subsequent time period as a result of the COVID-19 pandemic, which had a substantial impact on the daily functioning and mental health of societies worldwide, including the USA [
30,
31]. The global recession resulting from the COVID-19 pandemic also led to job loss among millions of people, producing a substantial economic impact on the USA that is expected to have long-term effects [
32].
When comparing the components included in the 2018 and present study, the updated estimates show a 12.8% increase in healthcare costs and a 56.5% reduction in productivity loss (i.e., absenteeism, presenteeism, and disability) compared to the prior year estimates. Compared to previous methods, the current study used the NSDUH data for assessing absenteeism days and US median daily wages to convert workdays lost into costs, which was a more conservative approach than in the prior work which used a commercial database for both workdays missed and associated lost wages given that commercially insured individuals generally have higher income than the general population. In addition, the previous work used a ratio approach of absenteeism to presenteeism workdays lost, which may have overestimated presenteeism-related costs, as shown by the relatively high importance of the sensitivity analysis on the presenteeism-related costs. Therefore, the current study used the ratio of absenteeism to presenteeism in an upper bound sensitivity analysis and a more conservative approach of reported presenteeism days from the literature as the base case analysis. With the use of updated input estimates and improvements in methodology, the overall incremental economic burden of MDD estimated in the current study remained higher as a result of the increasing MDD prevalence, the inclusion of several additional cost components (i.e., unemployment, all-cause mortality, and household-related costs), as well as the use of more recent sources for some cost component estimates.
Indeed, one of the key differentiators of the current study from previous estimations of the economic burden of MDD [
8,
33,
34] was the consideration of household-related costs. The spillover costs of MDD to adults living with individuals with MDD may be due to a variety of reasons, including the fact that household members (e.g., adult children or spouse) tend to be primary caregivers for those with mental health conditions [
35,
36]. The reduced annual income of adults living in a household with an individual with MDD that was used in this study is in line with the literature that caregivers tend to have reduced employment and work productivity because of their caregiving roles [
35,
37‐
39]. As the burden of MDD typically goes beyond the direct impact on the individual with MDD [
11], the current study adds to the literature by including the household-related cost component that is often overlooked in societal economic appraisals. Adopting a more holistic view in the assessment of burden of disease is especially important for recognizing the far-reaching impact of a condition on the individuals as well as their family members and caregivers.
In the current estimates of the economic burden of MDD in 2019, incremental costs of unemployment for women were negative. It is important to note that association does not imply causation, and there may be multiple factors that influence the employment rates of women with and without MDD. For instance, previous studies have suggested that individuals with MDD are less likely to get married and on average have fewer children [
40,
41]; the reduced responsibilities for childcare, which still largely lie with women, may partially explain the slightly lower unemployment costs for women with MDD compared to women without MDD. Furthermore, it may also be possible that the employment rate among women with MDD is influenced by other demographic or socioeconomic factors such as education status if women with MDD are more likely to have higher education levels or be employed in professions that are less affected by economic downturns, which could contribute to higher employment rates.
The incremental costs of all-cause mortality associated with MDD were estimated at $9.6 billion ($485 per adult with MDD). A third of the total count of suicides in the USA in 2019 (30,899 out of 45,861 suicides) were attributed to MDD, which accounted for 50% of the excess all-cause deaths among adults with MDD in 2019. Despite the large humanistic burden of premature mortality, the resulting economic burden accounted for a relatively low proportion of the total economic burden of MDD (2.9%) given that the opportunity costs of premature mortality were estimated to be attributable to a relatively small proportion of the MDD population (0.2%). On the basis of the current estimates, the economic burden of MDD appears to be substantial and above that of some other mental health conditions (e.g., anxiety [$89 billion], attention-deficit/hyperactivity disorder [ADHD; $123 billion], posttraumatic stress disorder [PTSD; $232 billion], bipolar disorder [$130 billion], schizophrenia [$187 billion]; all 2018 USD), as well as chronic physical health conditions (e.g., coronary heart disease [$199 billion]; 2018 USD) that have also been associated with a sizeable societal burden [
42]. Given that MDD is highly comorbid with other mental and physical health conditions [
7,
43], which may exert reciprocal impacts on disease severity and management, the burden of MDD is likely partially embodied in the economic assessments of other mental and physical health conditions. In essence, MDD is a costly condition, and its impacts may complicate the burden assessments of other conditions that are commonly comorbid with MDD.
The hypothetical simulation scenario associated with a rapid-acting novel therapy presented in this study demonstrates the potential for advancements in the treatment landscape of MDD to play a crucial role in alleviating the economic burden of MDD. On the basis of the study assumptions, such a novel therapy could reduce 7.7% of the incremental economic burden of MDD relative to the current standard of care, corresponding to approximately $1300 of cost savings per adult with MDD per year, or $2500 per treated adult with MDD. While the exact amount of cost savings would depend on market access, treatment utilization, and the efficacy and safety profile of such a therapy if it were to become available, it is worth noting that the availability of a more effective, rapid-acting therapy for MDD may increase the overall number of patients seeking treatment; thus, the current simulation scenario is potentially an underestimate of the impact of such a novel therapy by assuming that the number of treated patients stays constant. Meanwhile, although the simulation was hypothetical, by improving treatment of MDD, providing improved options, and increasing access to mental health care services, we may be able to reduce the number of people affected by MDD and improve the quality of life, functioning, and productivity for those who suffer from it. This would not only benefit individuals with MDD and their families but would also have the potential to reduce the societal and economic burden of the disorder. Although a rapid-acting novel therapy was simulated in this study, the same methodologies could be applied to assess the potential impact of any public health intervention (e.g., improved mental health professional training, workplace accommodation and health promotion programs, health insurance expansion, and increased mental health research funding [
44,
45]). Given work-related components were estimated to contribute to a large proportion of the incremental economic burden of MDD in this study, there should be increased public awareness around labor laws (e.g., the Americans with Disabilities Act and the Family and Medical Leave Act) that aim to improve employment opportunities and protect the rights of individuals with mental or physical impairment. Employer groups may also consider interventions that may help to reduce the strain on employees with MDD, which may ultimately improve work-related metrics and alleviate the associated economic burden.
Finally, it is worth noting that the estimated prevalence of MDD among US adults in 2019 was 7.8%, which was an increase from the previous estimate of 7.1% in 2018 [
8]. Results from a recent web survey in 2023 have also suggested that the lifetime prevalence of US adults diagnosed with MDD has increased by 10 percentage points since 2015 [
46]. As it was not possible in the current study to identify the factors associated with the rising prevalence of MDD over time, further studies are warranted to monitor trends of MDD and its associated economic burden, especially in light of the COVID-19 pandemic. The pandemic has brought fundamental changes to the lifestyle, work routine, and social relationships of the US population, and there could be long-lasting effects even after the pandemic subsides [
47]. Future studies should assess the potential persistence in mental health impacts and associated economic consequences of the pandemic, particularly among vulnerable populations like those with MDD and their families.
Limitations
The current study should be interpreted in light of several limitations. The incremental economic burden of MDD was estimated on the basis of the differential between inputs for adults with MDD and adults without MDD, and therefore should be interpreted as associations rather than causation without an attempt at establishing directionality in terms of the natural history of MDD and associated outcomes. Although the healthcare cost analyses were adjusted for demographic and comorbidity differences between adults with MDD and adults without MDD, the remaining inputs rely on the unadjusted differential between adults with MDD and adults without MDD stratified by gender. Owing to the absence of a single data source for calculating all cost components associated with MDD, the study methodology relies on multiple literature-based estimates; hence, the quality and accuracy of the cost estimates is limited by the available data, which may have resulted in the underestimation or overestimation of certain cost components. The prevalence of MDD was based on findings from the NSDUH, which was designed to generate a national probability sample of the US general population. However, using MDE data from NSDUH as a proxy for MDD and the possibility of self-report bias such as underreporting of depressive symptoms [
48] may have affected the true prevalence estimates. In addition, individuals with mild depressive symptoms (PHQ-9 score < 10) were assumed to not qualify for MDD in this study, but there may be mild cases of clinically diagnosed MDD within this spectrum, in which case the associated economic burden would not be captured. Finally, the rapid-acting novel therapy scenario was an exercise based on a hypothetical rate of early response within 2 weeks after initiation of treatment and only considered the immediate impact of increased rate of response/remission without adjustment for long-term societal reductions in the burden of MDD from a life-course perspective (e.g., lower rates of MDD leading to higher rates of education and subsequent employment over time). The assumption that all patients currently receiving a standard of care treatment would transition to a novel therapy is a modelling simplification and does not reflect the reality of treatment market access or the complexity of the management of MDD care and therefore likely represents an idealistic scenario. The novel therapy scenario was intended to illustrate the potential benefit of such therapy on the economic burden of MDD to highlight the importance of management of MDD and the capacity to reduce the societal burden of disease but should not be extrapolated beyond that objective.