International Journal of Environmental Research and Public Health Review Deaths of Despair: A Scoping Review on the Social Determinants of Drug Overdose, Alcohol-Related Liver Disease and Suicide Elisabet Beseran 1 , Juan M. Pericàs 1,2,3 , Lucinda Cash-Gibson 1,3,4 , Meritxell Ventura-Cots 2 , Keshia M. Pollack Porter 3,5,6 and Joan Benach 1,3,7, * 1 Research Group on Health Inequalities, Environment, and Employment Conditions, Pompeu Fabra University, 08002 Barcelona, Spain 2 Liver Unit, Internal Medicine Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute for Research, CIBERehd, 08036 Barcelona, Spain 3 Johns Hopkins University—Pompeu Fabra University Public Policy Center (UPF-BSM), 08002 Barcelona, Spain 4 UPF Barcelona School of Management, Pompeu Fabra University, 08008 Barcelona, Spain 5 Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON M5T 1P8, Canada 6 Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA 7 Ecological Humanities Research Group (GHECO), Universidad Autónoma de Madrid, 28049 Madrid, Spain * Correspondence: joan.benach@upf.edu Abstract: Background: There is a lack of consensus on the social determinants of Deaths of Despair (DoD), i.e., an increase in mortality attributed to drug overdose, alcohol-related liver disease, and suicide in the United States (USA) during recent years. The objective of this study was to review the scientific literature on DoD with the purpose of identifying relevant social determinants and Citation: Beseran, E.; Pericàs, J.M.; inequalities related to these mortality trends. Methods: Scoping review focusing on the period Cash-Gibson, L.; Ventura-Cots, M.; 2015–2022 based on PubMed search. Articles were selected according to the following inclusion Porter, K.M.P.; Benach, J. Deaths of criteria: published between 1 January 2000 and 31 October 2021; including empirical data; analyzed Despair: A Scoping Review on the DoD including the three causes defined by Case and Deaton; analyzed at least one social determinant; Social Determinants of Drug written in English; and studied DoD in the USA context only. Studies were excluded if they only Overdose, Alcohol-Related Liver analyzed adolescent populations. We synthesized our findings in a narrative report specifically Disease and Suicide. Int. J. Environ. addressing DoD by economic conditions, occupational hazards, educational level, geographical Res. Public Health 2022, 19, 12395. setting, and race/ethnicity. Results: Seventeen studies were included. Overall, findings identify https://doi.org/10.3390/ a progressive increase in deaths attributable to suicide, drug overdose, and alcohol-related liver ijerph191912395 disease in the USA in the last two decades. The literature concerning DoD and social determinants is Academic Editor: Paul B. Tchounwou relatively scarce and some determinants have been barely studied. However different, however, large Received: 16 August 2022 inequalities have been identified in the manner in which the causes of death embedded in the concept Accepted: 26 September 2022 of DoD affect different subpopulations, particularly African American, and Hispanic populations, but Published: 29 September 2022 blue collar-whites are also significantly impacted. Low socioeconomic position and education levels and working in jobs with high insecurity, unemployment, and living in rural areas were identified as Publisher’s Note: MDPI stays neutral the most relevant social determinants of DoD. Conclusions: There is a need for further research on with regard to jurisdictional claims in published maps and institutional affil- the structural and intermediate social determinants of DoD and social mechanisms. Intersectional iations. and systemic approaches are needed to better understand and tackle DoD and related inequalities. Keywords: death of despair; public health; social determinants of health; health inequalities Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article 1. Introduction distributed under the terms and Overall, mortality trends were declining in several high-income countries before the conditions of the Creative Commons COVID-19 pandemic started in 2020 [1], yet a significant increase in excess deaths has been Attribution (CC BY) license (https:// reported across continents since then, which has not only been attributable to SARS-CoV-2 creativecommons.org/licenses/by/ 4.0/). infection but also other causes. In the United States (USA), mortality due to drug overdoses, Int. J. Environ. Res. Public Health 2022, 19, 12395. https://doi.org/10.3390/ijerph191912395 https://www.mdpi.com/journal/ijerph Int. J. Environ. Res. Public Health 2022, 19, 12395 2 of 18 depressive and mental illness as well as alcohol consumption sharply increased during the COVID-19 lockdown period [2]. However, prior to the pandemic, mortality rates for certain groups of American citizens rose dramatically, mainly due to causes such as suicide, drug overdose, and liver disease due to alcohol abuse [3]. The misuse and addiction to opioids, including the prescription of pain relievers, heroin, and synthetic opioids [4], has been a public health concern for many years in the USA [5]. In 2015, Case and Deaton conducted a pivotal study [3] on the increase in deaths attributable to drug overdose, alcohol liver disease, and suicides between 1999 and 2013. They later labeled this phenomenon Deaths of Despair (DoD) [6]. This study was the first to document this reversal of mortality trends after decades and demonstrate this unique phenomenon in the USA. According to Case and Deaton [3], the largest increase in DoD was particularly among middle-aged non-Hispanic whites, especially those with lower levels of education. Between 1999 and 2013, the author calculated that all-cause mortality for less educated non-Hispanic whites increased by 134 per 100,000. Among this group, mortality due to poisonings rose 44.3 per 100,000, chronic liver disease rose 12.2 per 100,000, and intentional self-harm 44.3 per 100,000 [3]. Case and Deaton conceptualized despair as having an array of mechanisms causing self-harming behaviors that may underlie a common epidemic of pain and distress and also suggested that the Social Determinants of Health (SDH)—the societal conditions within which people live that shape and influence their health outcomes—play an important role [7]. “[DoD] come from a long-standing process of cumulative disadvantage for those with less than a college degree. The story is rooted in the labor market, but involves many aspects of life . . . Although we do not see the supply of opioids as the fundamental factor, the prescription of opioids for chronic pain added fuel to the flames, making the epidemic much worse than it otherwise would have been . . . Controlling opioids is an obvious priority, as is trying to counter the longer term negative effects of a poor labor market on marriage and child rearing, perhaps through a better safety net . . . .” [6]. There is consensus amongst researchers that the recent increase in self-harming atti- tudes such as suicides and drug abuse in the USA have joint characteristics. For instance, mental health issues, such as anxiety disorders, mood disorders, schizophrenia, and other psychotic disorders, are widely recognized as intermediate drivers [8]. At the structural level, a progressive erosion of social relationships, networks, institutions, and communities in large social strata mainly due to economic recessions is also recognized [9]. For instance, exposure to economic stagnation, declining incomes, and prospects as well as exit from the workforce could lead to despair-related behaviors [10]. Few authors have addressed the relationship between such intermediate drivers and the structural determinants of despair-related outcomes. The available evidence suggests a strong role in education attain- ment, geographical setting, and race/ethnicity [11–13]. However, the underlying causes and social mechanisms of DoD and inequalities in DoD-related mortality by social groups seem to be neglected in the current literature. Consequently, there is a lack of consensus among scholars and policymakers as to whether DoD constitutes a distinct epidemiological phenomenon and therefore requires a tailored investigational and interventional approach. Thus, the aim of this study is to review the scientific literature on DoD in the USA published in the health sciences field to identify relevant social determinants. 2. Materials and Methods This scoping review focused on the period from 2015 to the present date (31 April 2022) as DoD was first identified by Case and Deaton in 2015 [3]. A scoping review was chosen due to its exploratory nature and ability to identify and synthesize the evidence on a particular topic that has been limitedly explored [14]. Int. J. Environ. Res. Public Health 2022, 19, 12395 3 of 18 2.1. Search Strategy A search on the PubMed database was performed using the following terms and applied to the title, abstract, or keywords: (“deaths of despair” OR “despair premature deaths,” OR “mortality from despair”) AND (“social determinants of health” OR “health inequalities” OR “health disparities” OR “public health”). 2.2. Inclusion and Exclusion Criteria Studies were eligible for inclusion if they met the following criteria: (1) published between 1 January 2015 and 31 April 2022; (2) empirical (i.e., comments and editorials were excluded); (3) included all DoD categories as defined by Case and Deaton (suicide, acute illicit drug poisoning and alcohol-related deaths) [3,6]; (4) analyzed at least one SDH; (5) written in English; and (6) studied DoD in the USA context only. Studies were further excluded if they met the above inclusion criteria but only analyzed the adolescent population (12–18 years old). When analyzing deaths due to alcohol, Case and Deaton only included alcohol-related liver disease in DoD [3]; however, we considered alcohol-related deaths in more general terms following the criteria of subsequent authors [8,15–21]. 2.3. Data Extraction Articles were screened based on keywords, title, and abstract and then were assessed for full-text reading. Data extracted included study design, study objective, measures used, key findings, and limitations. Two independent reviewers (EB, JMP) selected and analyzed the relevant studies. For each study, the research questions, results, data, and limitations were identified. Findings were synthesized in a narrative report and study results were summarized in tables and qualitatively described. For the purpose of presenting thematic results in the review, six categories were created for different SDH: (1) economic conditions, referring to socioeconomic insecurity (i.e., income losses, unemployment, and loss of socioeconomic status); (2) occupation and employment conditions, encompassing job hazard risks; (3) education; for which categories were simplified into three: less than high school degree, intermediate and those with more than a college degree, (4) geographical setting, referring to rural vs. urban settings and the location within the USA; (5) race/ethnicity, and (6) gender. To provide an intersectional analysis, which considers multiple axes of inequalities, we also extracted the data about race/ethnicity in each paper included in each category. 2.4. Definitions Health inequalities refer to unfair, unjust, avoidable, and unnecessary (i.e., neither inevitable nor irremediable) and systematic health differences, within and between coun- tries due to underlying social structures and political, economic, and legal institutions [7]. Socioeconomic position is an aggregate concept that includes both resource-based and prestige-based measures, as linked to both childhood and adult social class position [7]. Job insecurity refers to the concern about whether one will have a job in the future [22]. Economic insecurity is the possibility of a decline in income and socioeconomic posi- tion/status [15]. Axes of health inequality are inequalities in the social structure due to social class, socioeconomic position, ethnicity, or race that influence the opportunities for having good health [23]. Occupational hazards refer to the characteristic factors of different jobs that may influence despair-related mortality trends [24]. 3. Results A total of 350 articles were identified using the search strategy (Figure 1). The initial screening by title led to the exclusion of duplicates and the initial exclusion of 195 studies that were not in line with the inclusion criteria. A review of abstracts of the remaining 155 resulted in the exclusion of 58 studies that did not address the topic of interest. Hence, 97 full-text articles were read for potential inclusion. A secondary search (i.e., a review of 3. Results A total of 350 articles were identified using the search strategy (Figure 1). The initial screening by title led to the exclusion of duplicates and the initial exclusion of 195 studies that were not in line with the inclusion criteria. A review of abstracts of the remaining 155 Int. J. Environ. Res. Public Health 2022, 19, 12395 resulted in the exclusion of 58 studies that did not address the topic of interest. Hence, 497of 18 full-text articles were read for potential inclusion. A secondary search (i.e., a review of the reference list of identified papers) resulted in two additional studies being included. At thethe lastreference stage oflist theofreview, identified papers)were 81 articles resulted in twobecause excluded additional thestudies studiesbeing included. did not assess At the last jointly stage potential the three of the review, causes81ofarticles DoD aswere excluded a common because theorstudies phenomenon did notdid not any assess assess SDHjointly the three or were potential editorials causes of leaving or comments, DoD as 21a common phenomenon or did not assess any eligible studies. SDH or were editorials or comments, leaving 21 eligible studies. Figure 1. Flowchart of analyzed studies. Figure 1. Flowchart of analyzed studies. The first study on DoD was published in 2015 by Case and Deaton [3], two studies wereThepublished first study in on 2017DoD was and [25,26], published the restin of 2015 by Case identified the literature and Deaton was[3], two studies published during were published 2019–2022 in 2017 [25,26], and [5,8,15–21,24,27–34]. Inthe restofofgeography, terms the literature identified most was published of the studies dur- were conducted ingwith 2019–2022 data of[5,8,15–21,24,27–34]. In terms participants that resided of geography, nationwide most of the studies were con- [3,8,15–18,20,21,25,29,30,32,34,35]. Only ducted with focused five studies data on of participants a single that resided Allnationwide USA state [24,27,28,31,33]. causes of DoD[3,8,15– were ag- gregated in the same cluster 18,20,21,25,29,30,32,34,35]. of analysis Only five in most on studies focused of the studies. a single USA Few stateauthors separately [24,27,28,31,33]. Allexamined causes of mortality DoD weretrends for each aggregated cause in the sameof death, clusterwith results in of analysis suggesting thatstudies. most of the the main Fewcontributor to DoD mortality authors separately examined was opioid-related mortality deaths trends for each[24,29,36]. Elevenwith cause of death, studies exam- results ined race/ethnicity suggesting that the main [3,17,19,20,24,25,28–30,34,35]. contributor to DoD mortality Case and wasDeaton [3] highlighted opioid-related deathsthat [24,29,36]. Eleven studies examined race/ethnicity [3,17,19,20,24,25,28–30,34,35]. Case and by DoD was restricted particularly among those aged 45–64. This finding was supported subsequent Deaton studies which [3] highlighted analyzed that DoD robust databases was restricted [20,25,27,35]. particularly among those aged 45–64. This finding was supported by subsequent studies which analyzed robust databases 3.1. Economic Conditions [20,25,27,35]. Seven studies [8,15–18,26,33] assessed direct measures of economic conditions related 3.1.toEconomic despair-related Conditionsoutcomes. The results and specific characteristics of each study are shown in Table 1. Seven studies [8,15–18,26,33] assessed direct measures of economic conditions related With regards to absolute income, only one study assessing the relationship between to despair-related outcomes. The results and specific characteristics of each study are the net worth of individuals’ income and the risk of dying due to despair-related causes shown in Table 1. was found: Zeglin and colleagues [27] analyzed the role of income alongside other SDH in DoD in Florida. Surprisingly, higher than average income (an average income in Florida is 43.000$ per year with a standard deviation of 7.21) was associated with higher mortality due to DoD. Authors hypothesized that “ . . . perhaps, in counties with above average income, there is lower comparative income utility, thus leading to greater despair and DoD-related behaviors” [27]. Int. J. Environ. Res. Public Health 2022, 19, 12395 5 of 18 Table 1. Studies addressing Deaths of Despair according to economic conditions. Sample, Region/State, Author Year Aim/s Methods Results Race/ethnicity Limitations Year of Data Collection From 2009 to 2018, the prevalence of deaths of alcohol-related, substance-related, and suicide-related diagnoses, Retrospective respectively, increased by To characterize study using 37%, 94%, and 170% and Healthcare rates of healthcare There is an were associated with higher database with clinically claims Details on incomplete physical and mental 12,144,252 documented database race/ethnicity nature of social conditions, especially participants. Brignone DoD over the extracted from were not determinants 2020 among those with USA. E, et al. [8] last decade Highmark, available for of health data Affordable Care Act or Data was and identify with 10 years the sample in Medicare coverage relative collected from sociodemo- of follow-up. used. administrative to commercial coverage 2009–2018 graphic risk Use of logistic health records. (Adjusted Odds Ratio factors. regression (AOR) 1.30, 1.24 to 1.37; modeling. AOR 1.51, 1.46 to 1.55). Overall, odds for current-year diagnosis were higher among men (AOR 1.49, 95% CI 1.47 to 1.51). Deaths were Counties in the highest counted only tertile of economic in smaller The study only insecurity in 2000 and 2010 counties. Ecological estimated had 41% (95% CI: 1.36, 1.47) Approximately longitudinal associations higher midlife mortality 10% of study. Measure among all Evaluate the rates at baseline and a rate counties had economic races in the association of increase of 2% more per missing data Sample size insecurity subgroup of between 5-year period (95% CI: 1.00, on our primary not available using counties where changes in 1.03) than counties with outcome. in the USA. Knapp EA, indicators from non-Hispanic 2019 economic stable low economic The measure of Data were et al. [15] the Census and White death insecurity and insecurity. economic collected from Federal rates were not increases in 20% of counties insecurity may 2000–2010 Reserve Bank missing. DoD during experienced an increase in mask in USA The racial 2000–2015 economic insecurity intercounty counties for composition between 2000 and 2010. variation. the years 2000 did not The regions experiencing a Some of these and 2010. account for more acute increase in changes seen differences. economic insecurity were may be due to the Midwest and South. changes in the coding. Higher than average income (p = 0.007), median age (p < 0.001), and mental health professionals in a The removal of Florida county (p = 0.027) 10% of the were associated with counties from Determine significantly higher DoD analysis due to Data for all 67 what rates in that county. Higher outliers Florida country-level than average levels of Background Race was not Counties. Zeglin RJ, social education (p = 0.066) and 2019 regression retained in the Small sample Florida, USA. et al. [27] determinants recent checkups in a Florida methodology final model. size Data was of health are county (p = 0.046) were collected in associated with associated with a The study did 2018. DoD in Florida significant decrease in DoD not address in that county. Also, the assessing for interaction between income regional effects and age was significant in the negative direction (p = 0.04) This accounts for 44% of the variance in county level. Int. J. Environ. Res. Public Health 2022, 19, 12395 6 of 18 Table 1. Cont. Sample, Region/State, Author Year Aim/s Methods Results Race/ethnicity Limitations Year of Data Collection The models do not account for Extract data the selection of To assess from the Financial losses mediate unobserved empirically the National 20% of the association characteristics 8.000 significance of Longitudinal between drug use and not included in responders financial losses Study of suicide ideation among Add USA Fishman as a key Did not report Adolescent those with those with a Health.The Data were SH, et al. 2021 mechanism racial and Adult high school degree or less. results apply to collected from [16] through which differences. Health (Add It is possible that other the association 1994–1995 education is Health). Use of mechanisms operate between young 2007–2008 associated with logistic through financial loss to adulthood and 2016–2018 a higher risk of regression influence DoD mortality. middle DoD. modeling. adulthood but may not apply to older ages. One Standard Deviation positive shock in housing wealth increases the Data were probability of an Sample size is extracted from To assess the improvement in not available. the Panel Did not find Housing Jou A, et al. role of housing self-reported health by USA. 2020 Study of racial Wealth, Health [17] as a driver of 1.13% points and decreases Data was Income differences. and DoD DoD. the drug-related mortality collected from Dynamics rate by 0.27%. 1984–2013. (PSDI). These results are not significant for alcohol or suicide death rates. A 10% minimum wage Potential increase reduces non-drug heterogeneity To investigate suicides among by race or Sample size if minimum Did not Causal models low-educated adults by 2.7 ethnicity was not available. wages and estimate Dow WH, (difference-in- percent, and the not USA. 2020 earn income heterogeneity et al. [18] differences comparable Earned Income estimatedThe Data was tax mitigate by race or models) Tax Credit figure is 3.0 models did not collected from the rise of DoD ethnicity. percent. There are no pick up 1999–2017 significant effects on drug- long-run or alcohol-related mortality. effects Data was extracted from CDC’s National Center for Health Statistics. It provides death Areas more exposed to a certificates plausibly exogenous The from 1990 to change in international associations The findings To investigate All death 2013. trade policy exhibit relative between do not provide the impact of a certificates in Age-adjusted increases in fatal drug exogenous an assessment Pierce R, large and USA. 2020 and crude rates overdoses (2 to 3 per trade in USA of the overall et al. [35] persistent Data were were 100,000), specifically among policy and welfare impact economic collected from calculated. whites, controlling for drug overdoses of shock on DoD. 1990–2013 Baseline state-level legislation were seen only liberalization. differences pertaining to opioid among whites. specifications availability and health care. to examine the link between deaths of despair and permanent normal trade relations. Int. J. Environ. Res. Public Health 2022, 19, 12395 7 of 18 Income insecurity is another factor that has been associated with despair-related mortality. In USA counties, higher economic insecurity has been associated with higher rates of DoD. Knap et al. [16] showed that 20% of USA counties experienced an increase in economic insecurity between 2000 and 2010. Moreover, financial reductions, i.e., loss of assets and loss of income, were also factors that contributed to despair-related mortality [16]. These financial losses were found to mediate 20% of the relation between education with drugs and suicide ideation. This suggests that financial losses among those with lower education levels are an important driver of despair-related behaviors. Conversely, Jou et al. explored housing as another driver of despair mortality [17]. This research found that households that experienced an unexpected positive shock in their housing wealth when they sell their houses had a decreased drug-related mortality rate by 0.27. Medical coverage was analyzed only in one study [8]. The data were extracted from a Healthcare database with participants that resided nationwide, but most data came from Pennsylvania, West Virginia, and Delaware. Those with the Affordable Care Act or Medicare Coverage were seen to experience respectively 1.3- and 1.5-fold higher risk of suffering DoD relative to those with commercial coverage [8]. The main USA policies that are used to increase income among low-earning workers are Earned Income Tax Credit and Minimum Wages. The use of these policies has been linked to a reduction in non-drug suicides [18]. In summary, our findings show that the main economical drivers related to DoD include a decline in income and assets as well as medical coverage. The perception of worsening social status and economic hardship with respect to close contacts and society overall also seems to have a detrimental effect. Policies that improve economic conditions among low-earning workers appear to be protective against DoD. 3.2. Occupational Hazards Seven studies analyzed specific occupational risk factors related to despair mortal- ity [24,26,28,30–33]. Occupational hazards refer to the characteristic factors of different jobs that may influence despair-related mortality trends [24]. Details of the studies are shown in Table 2. Table 2. Studies addressing Deaths of Despair according to occupational hazards. Sample, Region/State, Author Year Aim/s Methods Results Race/Ethnicity Limitations Year Data Collection, PMRs for deaths due to drug overdoses, suicide, and The occupational To assess alcoholic liver Occupations with a codes only occupational disease were higher risk of Deads of consider the Sample size differences in obtained from Despair were: occupation of the not available. Differences proportional the National construction, architects, deceased USA. between Rayhall, mortality ratios Occupational food preparation, and individual during Data were 2022 race/ethnicity et al. [32] (PMRs) and Mortality service. In addition, the majority of collected from: were not trends in these Surveillance personal care and home their life. It does 1985–1999 reported. PMRs due to system. Data aides had the highest not consider the 2003–2004 the DoD in the came from increase in death due to occupation of the 2007–2014 United States various states for deaths of despair. individual when the years 1985 to they passed. 1998, 1999, 2003 to 2004, and 2007 to 2014. Int. J. Environ. Res. Public Health 2022, 19, 12395 8 of 18 Table 2. Cont. Sample, Region/State, Author Year Aim/s Methods Results Race/Ethnicity Limitations Year Data Collection, Deaths certificated due The highest mortality to DoD were rate for DoDs was Misclassification To explore coded by the among medical with respect to Sample size DoD mortality occupation of the assistants; nursing, Differences occupation, as not available rates among healthcare psychiatric, and home between death certificates Massachusetts, Kaki S healthcare workers. 2021 health aides; race/ethnicity have only USA. et al. [33] workers in Mortality rates miscellaneous; health were not information about Data were Massachusetts and rate ratios technologists and reported, the usual collected from from 2011 to were calculated technicians; emergency occupation of the 2011–2015 2015 according to the medical technicians, individual. occupation of and paramedics. healthcare workers. Death certificates were obtained from the To determine Massachusetts Unique specific the differences Department of fishery in DoD Public Health’s 26,000 deats Fishermen were more characteristics were between Registry of Vital certificates than four times more Racial not determined. Fulmer fisherman and Records and records likely to die from differences It was not possible S, et al. 2021 non-fisherman Statistics. The Massachusetts, opioid poisoning than were not to differentiate [31] workers in two mortality USA non-fishermen reported. between Massachusetts analysis was 2000–2014 residents. recreational use fishing ports used to quantify and prescription between the differences use of opioids. 2000–2014 between fishing and non-fishing workers residing in the two cities. The measures of exposure utilized Usual occupation for this study were The highest number of information was assessed at the all deaths of despair collected from group level. Within occurred in death certificates groups, there is To determine occupations with injury of Massachusetts likely variation in whether rates of at least 100 per residents aged exposure and differences in 10,000 full-time 16–64 with individual-level the risk of DoD workers. Sample size relevant causes misclassification. were Workers in occupations not available of death between The wide variety of associated with with more job Massachusetts, Hawkins 2005 and 2015. Racial data sources that the rate of insecurity had higher USA D, et al. 2021 These data were differences were combined at occupational rates of DoD (RR 1.05 Data were [24] combined with were not found the national level, injuries and (1.00, 1.09)). collected from occupation-level certain occupations illnesses, job Rates of DoD increased 2005–2015. data about and workers could insecurity, and most rapidly for occupational have been temporal occupations with the injuries and misclassified with changes in increasing prevalence illnesses, job respect to the employment. of workers employed insecurity, and exposures in non-standard work non-standard analyzed. Death arrangements (RR 7.6 work certificates only (6.7, 8.5)) arrangements. have information about the usual occupation. Int. J. Environ. Res. Public Health 2022, 19, 12395 9 of 18 Table 2. Cont. Sample, Region/State, Author Year Aim/s Methods Results Race/Ethnicity Limitations Year Data Collection, Mortality rates Death certificates from deaths of The occupation for deaths due to despair caused information listed poisoning, among white, on a death suicides, and non- Hispanics certificate is the alcoholic liver DoD increased more were about “usual” occupation To explore disease occurring Sample size than 50% between 2000 50% higher in an individual’s mortality rates in Massachusetts not available and 2004 and than those lifetime. and trends from 2000 to 2015 Massachusetts, Hawkins 2011–2015. among according to were collected USA D, et al. 2020 Workers with elevated Hispanics of all It is not known the occupation and coded Data were [28] trends for these deaths races and whether those who of workers according to the collected from were construction, black, died were working who died from occupation of the 2000–2015 farming, fishing, and non-Hispanics. at the time of death, DoD deceased. forestry workers. Asian, which may have Mortality rates non-Hispanics resulted in some and trends in accounted for misclassification of mortality were less than 1% of causes of death. calculated for all deaths of each occupation. despair. Temporal trends Adults in service jobs were not assessed (OR 3.10 [1.38–6.94]), because of the manual labor (OR 2.22 moderate number [1.00–4.96]), and of deaths avail- transport occupations able.Employment (OR 2.38 [1.08–5.25]) status and had two to three times occupation were To estimate the risk of accidental obtained at the associations poisoning mortality. time of the survey between an Data of 360,146 Health professionals and may change Sample size individual’s adults aged exhibited the highest during the not available occupation and 25–65 from the accidental poisoning Racial follow-up. USA. Gutin I, employment National Health mortality risk (OR 3.35 2020 differences are The accidental Data were et al. [30] status and Interview [1.18–9.47]). Long-term not found. poisoning category collected from alcoholic liver Survey-Linked unemployed adults encompasses a 1997–2015 disease, mortality Files had elevated risk of diverse set of suicide, or (1997–2015) accidental poisoning deaths. poisoning (OR 6.44 Comprehensive mortality risk. [2.69–15.41]).Adults not data on individuals’ in the labor force had workplace double the suicide risk experiences, (2.28 [1.49–3.49]) and exposures, and seven times the rewards would accidental poisoning allow for a better risk (OR 12.71 measure of [7.46–21.67]). “precariousness.” Mortality rates Mortality rates are were obtained higher among counties from the U.S with socioeconomically Centers for There was no To determine disadvantaged Disease Control disaggregation by Sample size associations residents, declines in and Prevention’s sex or age. not available between income, military Racial Wide-Ranging Death certificates USA. Monnat county factors residents, and differences 2017 Online Data for might misclassify Data were [26] and drug, population aged 65+. were not Epidemiological the cause of death. collected from alcohol, and Counties with reported. Research Changes in 2011–2015 suicide occupational losses 2006–2015. mortality were not mortality rates. experience higher Spatial analyses examined. mortality rates due to were conducted alcohol, suicide, and on country-level drugs. factors. Int. J. Environ. Res. Public Health 2022, 19, 12395 10 of 18 Hawkins et al. analyzed deaths certificates data in Massachusetts for which the cause of death was a despair-related behavior [28]. The authors found that blue-collar workers exhibited particularly elevated risk for DoD, and among them, those with higher despair- related mortality risk were construction, farming, fishing, and forestry workers [28]. The specific risk for DoD among fishing workers in Massachusetts was supported by Fulmer S et al. study [31]. They found that commercial fishermen were four times more likely to die of opioid poisoning than non-fishermen living in the same fishing ports [31]. When analyzing data for the National Occupation Mortality Surveillance in the USA, Rayhsall et al. found that occupations at higher risk were construction, architects, food, and preparation and service. However, those with the highest increase in DoD were personal care, service, and home aides [32]. Hawkins et al. [24] also studied the contribution of occupation-specific risk factors to DoD in Massachusetts and found that high economic insecurity was one of the most important factors affecting DoD. This economic insecurity was measured as self-reported insecurity by 12% or more of the workers. The occupations which experienced higher economic insecurity were highlighted to be those which suffered higher rates of DoD, particularly opioid-related deaths [24]. Despite the specific risk factors related to each occupation, unemployment and being out of the labor force have been identified as key factors for premature despair-related mortality. Gutin et al. found that managerial/professional administrative groups had an estimated mortality rate of 2.88 per 100,000 individuals compared to 9 deaths/100,000 among unemployed adults, 13.63 deaths among never employed adults, and 19.32 deaths among those not in the labor force [30]. Moreover, this study also showed that there were differences depending on the cause of death among working-aged adults: recent job loss was strongly associated with suicide mortality whereas exit to the labor force was strongly associated with drug poisoning risk [30]. According to Monnat, counties with occupational losses in manufacturing industries are seen to be those with higher deaths of alcohol-, suicide- and drug-related deaths [26]. Under some circumstances, it appears that high-status jobs can also entail a higher risk of DoD. In Gutin et al., health professionals were found to suffer a two-to-four-fold higher accidental poisoning risk relative to adults in managerial/administrative positions. In addition, adults in service exhibited two to three times the risk of mortality from accidental poisoning compared to the same group [30]. Kaki S. et al. studied DoD among healthcare workers in Massachusetts; using death certificated data for 2011–2015, they analyzed the causes of death by occupation. The authors pointed out that the ones that presented higher mortality rates for DoD were medical assistants, nursing, psychiatric, and home health aides; miscellaneous; health technologists and technicians; emergency medical technicians, and paramedics [33]. In summary, employment status and type of employment are factors that were identi- fied to be associated with despair-related mortality. More specifically, although blue-collar jobs exhibited the highest risk of despair-related mortality, not working and specific risk occupation factors lead also to high despair-related behaviors among other occupations apart from blue-collar jobs. 3.3. Education Level Four studies [3,19,29,34] study the relationship between DoD and educational level. Details of the studies are shown in Table 3. Two studies [16,18] addressing the linkages between income and educational level with regard to DoD are shown in Table 1. Int. J. Environ. Res. Public Health 2022, 19, 12395 11 of 18 Table 3. Studies addressing Deaths of Despair according to education level. Sample, State/Region, Author Year Aim/s Methods Results Race/Ethnicity Limitations Year Data Collection, Region Over the 15-year period, midlife all-cause mortality fell by more Data extracted than 200 per 100,000 for from CDC Wonder black non-Hispanics, Compressed and and by more than 60 To analyze the Detailed mortality per 100,000 for Sample size mortality files Ethnicity and Hispanics. White There is an No mortality not available Case A, trends in the educational data non-Hispanic mortality increase in trends analyzed USA. et al. 2015 USA were extracted rose by 34 per 100,000 non-Hispanic from 2013 Data was [3] population of from the American for ages 45–54. The mortality. onwards. collected from all-cause Community change in all-cause 1999–2013 deaths. Surveys and before mortality for white 2000 from Popular non-Hispanics 45–54 is Surveys. largely accounted for by an increasing death rate in drug and alcohol poisoning and suicide. Data were extracted from the National To test if the Longitudinal Study Indicators may indicators of of Adolescent to not completely despairs are Adult Health. The Generalized increase in There is a capture all rising among individuals were multiple despair general domains of 18,446 middle-aged non-Hispanic indicators among all increase in despair. responders Gaydosh US adults. To White, White, Black, and despair across USA. L, et al. 2019 test if this rise non-Hispanic Hispanic adults in their racial/ethnic, The authors did Data were [29] is concentrated Black, or Hispanic. 30s. educational, not examine collected from among Changes in Midlife mortality and adults in their 1994–2017. low-educated indicators of increased across geographical 30s because of white adults despair from racial/ethnic groups. groups. the lack of data and in rural adolescence to in Add Health areas. adulthood were sample. examined using multilevel regression analysis. Drug overdose deaths Using data from increased over the The Census and Vital period 1990 and 2015, contribution of Statistics, the particularly in the drug overdose 2,151,890 men authors applied 25–64 years old group deaths Deaths due to and 2,718,198 table methods to (73% and 44% for men increased opioids may be women To test the calculate Geronimus and women, substantially undercounted on USA, not empirical cause-specific years AT, et al. 2019 respectively), especially over the study death certificates. state/region evidence of of life lost between [19] for Whites but trivially period for specified. DoD ages 25 and 84 by for blacks. Both blacks whites, Deaths may be Data were sex and and whites show particularly in misclassified. collected from educational rank increased mortality the 25- to 1990–2015. for non-Hispanic between the lowest and 64-year-old age blacks and whites highest education group. in 1990 and 2015. categories. Int. J. Environ. Res. Public Health 2022, 19, 12395 12 of 18 Table 3. Cont. Sample, State/Region, Author Year Aim/s Methods Results Race/Ethnicity Limitations Year Data Collection, Region Administrative, survey data, trends, and correlations between race, age, Rising white mortality education-specific is not restricted to the It is difficult to mortality, and lowest education completely To investigate economic and bracket and is isolate the Sample size if mortality social indicators occurring deeper into influence of not available increases are were examined to the educational Republican vote USA, not Siddiqi attributable to Mortality rates determine whether distribution. Parallel share because of state/region A, et al. 2019 (false) for Blacks are changes in the trends of economic the interconnect- specified. [34] perceptions of not rising. Republican share factors (and more edness of this Data were whites that of voters during adverse levels) of these variable with collected from they are losing presidential factors were being other 2000–2016. social status. elections were experienced by blacks, socioeconomic associated with whose mortality rates conditions. changes in are not rising. working-age white mortality from 2000 to 2016. Educational differences depending on the cause of death had also been reported. Several studies found associations between lower education levels and higher risks of DoD mortality. Case and Deaton reported that DoD was particularly higher among the lesser educated group [3]. In concordance, Zeglin et al. found a significant association between higher-than-average levels of education and a decrease in DoD in Florida [27]. It was found that education disparity was more striking for opioid-related deaths than for suicide or alcohol-related deaths. These differences accounted for 73% and 44%, respectively, for men and women, in drug mortality between low and high education groups [19]. Another study showed that despair-related mortality rates among those with a high-school degree or less were five times higher than those with a college degree, especially for opioid-related deaths [28]. As for the relationship between educational level and income, Dow et al. reported that a 10% increase in minimum wage was associated with a 2.7% reduction in suicide deaths for less-educated adults [18]. Moreover, for the earned income tax credit policy, a 10% higher maximum credit reduces suicide by nearly 3%. However, there were no statistically significant effects among the highest education groups [18]. Regarding the role of financial losses, those were seen to be a meaningful mechanism that promotes DoD especially among the lowest educated population. Financial losses accounted for 20% of the association of education with suicide and drug use [16]. Healthcare professionals constitute an exceptional group when considering the causes of DoD and educational attainment since they exhibit one of the highest accidental poison- ing and drug overdose risks [29,30]. In summary, lower education attainment has been shown to play a crucial role in rising despair mortality trends. However, there is controversy regarding whether this despair-increased mortality is restricted only to the low education level group. The field of work might play a crucial role. 3.4. Geographical Settings Three studies analyzed geographical settings [20,25,35]. Details of the studies can be seen in Table 4. Int. J. Environ. Res. Public Health 2022, 19, 12395 13 of 18 Table 4. Studies addressing Deaths of Despair according to geographical conditions. Sample, Year State/Region, Author Year Aim/s Methods Results Race/ethnicity Limitations Data Collection, Region Obtain all-cause To examine and metropolitan The study only cause-specific The non- versus non- examined the 9,211,413 deaths mortality rates metropolitan metropolitan and 81% of the white in metro counties by sex and age working-age intra-non- non-metropolitan population.The and 2,465,300 group (25–44 and mortality metropolitan mortality death rate analysis did not deaths in 45–64). Rates are penalty is Monnat all-cause-specific increase is due to adjust for nonmetro 2020 age-adjusted growing for all SM [20] mortality trends increases in drugs, compositional counties within each ethnic groups among working alcohol, suicide, and differences.The USA. 20-year age and especially age (25–64) mental/behavioral study only Data were group using for non-Hispanic disorders (DoD). divided collected from 10-year non-Hispanic males and two-division and 1990–2018. population whites. females economic types. counts and 1990–2018. weights. Death rates in rural subpopulations for all races/ethnicities increased among those aged 25 to 64 years by 6%, whereas Calculate large urban, cause-specific suburban, and small death rates using The study was or medium Compressed Deaths of limited by the metropolitan To evaluate Mortality File, despair were lack of Sample size not subpopulations had trends in National Center most information available decreases in death Stein premature deaths for Health pronounced about the USA. rates by 2% to 20%. EM, et al. 2017 by cause of Statistic data for among educational and Data were These disparities [25] death, age, race, adults 25 to 64 non-Hispanic economic status collected from were most and urbanization years [two whites relative of descendants 1999–2001 and pronounced in level in the USA. periods to other racial and the effects of 2013–2015. Whites relative to 1999–2001 and groups. racial/ethnic other racial/ethnic 2013–2015]. misclassification. subpopulations and Define 48 among those aged 45 subpopulations to 54 years. Most increases in death rates were attributable to suicide, poisoning, and liver disease. Use of 1990–2016 Multiple Cause Mortality from drug Estimate the of Death data overdose, suicide, contributions of files to tabulate and alcohol-related four key age deaths by age, causes of death Analyses did not groups to Sample size not sex, increased and adjust for changes in life The study only available race/ethnicity, contributed to life compositional Elo IT, expectancy at focused on USA 2019 cause of death, expectancy differences. The et al. [21] birth between non-Hispanic Data were county, and year. reductions across the study focused on 1990 and 2016 by groups collected from These data were metropolitan and Non-Hispanic metropolitan- 1990–2016. combined to no-metropolitan whites. nonmetropolitan estimate categories, especially status and age-specific from a drug region. death rates for all overdose. causes. Stein et al. conducted a nationwide study relying on the Compressed Mortality File, National Center for Health Statistics data for adults aged 25 to 64 years, encompassing 48 subpopulations and two time periods: 1999 to 2001 and 2013 to 2015 [25]. The main findings included an 8% decline in age-adjusted premature death rates for all adults in both sub-periods, with decreases in 39 of the 48 subpopulations. Most decreases in death Int. J. Environ. Res. Public Health 2022, 19, 12395 14 of 18 rates were attributable to HIV, cardiovascular disease, and cancer, whereas most increases in death rates were attributable to suicide, poisoning, and liver disease. All nine subpopu- lations with increased death rates were non-Hispanic Whites, largely outside large urban areas [24]. However, others reported some differences depending on the cause of death. For instance, in analyzing mortality trends in non-Hispanic White Americans, Monnat found that suicide rates increased among both rural and urban areas, but the increase was larger in the former [23]. Meanwhile, drug poisoning risk was higher in metropolitan areas. Another relevant finding of the study involved large divisional disparities, with particularly poor trends in New England, South Atlantic, East South Central, West South Central, and Appalachia and more favorable trends in the Mid-Atlantic, Mountain, and Pacific [20]. In concordance with these findings, Elo et al. also found that drug poisoning risk was higher in metropolitan areas and that this mortality had a large impact in the Appalachian, East South Central, and New England regions and the smallest in the Pacific region [21]. Regarding economic heterogeneity within rural counties, only one study was found [20]. Mining-dependent counties were found to experience the highest despair-related mortality rates. In contrast, in farming-dependent counties death rates were the lowest. There also were differences depending on the location of the counties, rural southern experienced the highest absolute mortality trends [20]. In summary, the geographical setting appears to be a key driver of DoD trends, with rural areas exhibiting the worst despair-related mortality outcomes. Among rural settings, Despair-related mortality inequalities seem to be higher in Southern states in comparison with Northern states. 3.5. Ethnicity/Race The first study on DoD by Case and Deaton attributed this mortality, especially to non-Hispanic White subgroups [3]. Ulterior studies supported this hypothesis [20,25,28,35]. Notably, several papers only focused their analysis on the non-Hispanic White population group [8,17,21]. Other authors have controlled for race/ethnicity in different studies and did not find significant differences between racial/ethnic groups [16–19,24,30]. In addition, some other scholars found that DoD was also a concern for other subgroups [20,29]. For instance, Gaydosh et al. showed that despair-related behaviors were increasing among African American, White, and Hispanic populations [29]. In short, there is controversy about the social groups affected by DoD. Even though the phenomenon of DoD was firstly attributed to non-Hispanic Whites exclusively, recent research has pointed out that these trends in mortality are extensible to other ethnic/race subgroups. 4. Discussion Despite DoD being a relevant phenomenon that has attained a lot of attention in the USA and worldwide, our review revealed that studies on the social determinants of DoD are relatively scarce in health sciences literature. Overall, our findings suggest that DoD can be defined as a cohesive phenomenon that has occurred in the USA since the early 2000s, i.e., there has been a progressive increase in deaths attributable to suicide, drug overdose, and alcohol abuse. In addition, it appears that large inequalities explain how DoD-related causes of death affect different subpopulations. Economic conditions, lower education levels, working in jobs with high insecurity, and being unemployed and living in rural areas appear the most relevant SDH impacting the rates of DoD. Finally, while Case and Deaton claimed that DoD is a phenomenon that essentially affects non-Hispanic Whites [3], several studies have since shown that there are also other ethnic and racial groups that are affected. These findings suggest that public policies should take into account these large social inequalities to prevent DoD among the population. In addition, this study points out the need for further studies to use an intersectional approach to better understand the root causes and social mechanisms of DoD. Int. J. Environ. Res. Public Health 2022, 19, 12395 15 of 18 The decline in economic conditions for vast strata of the American population seems to be a major driver of despair-related mortality trends. The deterioration of economic conditions encompasses both objective changes, e.g., lower relative and/or absolute income and socioeconomic position/status, and subjective phenomena such as a perceived frustra- tion with personal and family expectations. The evolution of economic perspectives for the middle class triggered by the aftermath of the 2007–2013 economic crisis has had unequal impacts across Western countries and within countries. Blue collar American workers have generally experienced either stagnation or worsening of economic prospects since the sev- enties, and therefore frequently share an acute sense of being vanished from the ascending social ladder from which benefited their parents or grandparents [25]. Although other population groups, for instance, African Americans, have the worst absolute mortality outcomes [34], the sense of social status decline in non-Hispanic Whites makes this group more vulnerable to self-harming behaviors driven by increasingly poorer mental health status [34,35,37]. In accordance, previous literature has identified a relationship between lesser perceived social status and depressive symptoms [36,38]. Frustrated expectations might be one of the main mechanisms that promote despair among low and middle-class middle-aged Americans. Remarkably, Zeglin et al. found that in Florida higher income was associated with a higher risk of mortality due to DoD [27]. This unexpected finding highlights the need of considering specific mechanisms and heterogeneity by territory. The links between economic insecurity and worst mental health, including suicide rates, have been well-known for a long time [39–41]. The increase in economic insecurity in the USA, particularly in certain states, was strongly associated with job externalization (e.g., Michigan), the 2007–2013 crisis, and more recently to the COVID-19 pandemic. Burgeoning economic insecurity has led to an epidemic of depression and other mental health issues linked to a sharp increase in suicides and drug-related issues [42]. Occupation, and particularly the type of job, insecurity, and unemployment are also critical factors in the frequency and distribution of despair-related deaths. Precarious em- ployment, characterized by limited financial security, perpetual employment instability, and poor workplace conditions, is progressively affecting greater segments of the American pop- ulation [43]. Precarious employment is closely linked to anxiety and stress, both precursors of self-damaging behaviors [33], which are also a well-known consequence of unemploy- ment, including suicide and drug overdose [44,45]. Interestingly, some studies suggest that high-status jobs also have increased despair-related mortality. For instance, health professionals exhibit the highest drug mortality risk, which is only partially attributable to easy occupational access to opioids [46]. The greater risk of DoD in the lesser educated population is likely underpinning wider social inequalities. Higher levels of education are known to improve public health and to be protective against poor health outcomes [47]. In contrast, lower levels of education have been associated with a higher risk of suicide and poorer mental health [48]. However, it is unclear if despair is only restricted to the lowest education group or if it is rather a proxy of socioeconomic position as a central axis of inequality that is affected by other social mechanisms, e.g., labor exploitation, discrimination, or racism. Studies have found that, in general, residents of rural areas experience poorer health outcomes than their urban counterparts [49], and this review suggests that this is also the case for DoD in the USA. Rural communities may have fewer opportunities for gainful employment and experience hardship and difficulties in access to quality health care. Plus, higher isolation and stigmatization of mental illness may promote differences in health behaviors [24]. Moreover, there are widening inequalities across USA states and counties in the incidence of DoD, which underlies the concentration of poorer combinations of social determinants of health in certain American territories. In the analysis of race and ethnicity, this review encountered diverse results. Some studies found that DoD was higher among White Non-Hispanic Americans. Remarkably, several studies only focused their analysis on this population subgroup [50,51]. Some authors found that other racial groups, for instance, African and Hispanic Americans, were Int. J. Environ. Res. Public Health 2022, 19, 12395 16 of 18 particularly at risk of DoD behaviors. In concordance, Tilstra et al. showed that African Americans exhibited similar despair-related mortality trends to White Americans [52]. These divergent findings suggest the need for additional research into these differences by racial and ethnic groups. We acknowledge some limitations of this scoping review. First, only papers published in English were included in this review. Second, our review is focused on DoD as a specifi- cally USA phenomenon, thus likely neglecting similar phenomena elsewhere. However, DoD has been also analyzed in other countries [53]. Third, only the PubMed database was searched. Finally, some SDH, such as gender differences were not found because they were little explored in DoD literature, despite differences in alcohol consumption, suicide, and illicit drug behaviors by sex having been reported previously [54,55]. 5. Conclusions DoD, i.e., illicit drug poisoning, suicide, and alcohol-related deaths, have sent USA life expectancy falling for several years, making it a national public health concern. Al- though DoD has been studied more frequently in some USA counties rather than others, is a countrywide epidemic that warrants systemic investigation. Our review found that studies on the social determinants of DoD in the health sciences literature are relatively scarce. Findings from the available literature suggest that the main drivers of DoD and its associated inequalities are the decline in socioeconomic positions and income, as well as rurality and occupation-specific hazards. Low- and middle-income populations and middle-aged Americans are disproportionately affected, and some studies suggest that this is a problem mostly affecting non-Hispanic Whites, although other racial groups such as African Americans and Hispanic seem to be affected too. This review identified a number of gaps in the literature; first, a general lack of intersectional approaches used in the study of DoD and a tendency to concentrate on specific subpopulations, mostly Whites, often neglecting other subpopulations, e.g., African American or Latino women, migrants or homeless persons [56]. Comprehensive studies analyzing the root causes are limited in the currently available health science literature. While some intermediate SDH have been studied (such as unemployment, economic insecurity, and education), others have not been thoroughly addressed (such as access to healthcare), nor have the social mechanisms (such as racism, discrimination, and exploitation) been explored. More research is needed on the structural determinants of despair-related mortality to identify social, physical, economic, and political factors that shape despair-related behaviors and systematically different mortality outcomes, as well as the social mechanisms involved [57]. Intersectional and systemic approaches will also need to be applied. This information can be used to inform the design of effective interventions aiming to reduce DoD and inequalities in DoD outcomes and tackle this national public health crisis. Author Contributions: Conceptualization, E.B., J.M.P. and J.B.; methodology, E.B., J.M.P., J.B.; val- idation, L.C.-G., M.V.-C. and K.M.P.P.; formal analysis, E.B.; investigation, J.M.P., L.C.-G., M.V.-C.; resources, J.B.; data curation, E.B.; writing—original draft preparation, E.B., J.M.P.; writing—review and editing, L.C.-G., M.V.-C., K.M.P.P., J.B. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: Data on the search strategy and analyses will be made available upon request. Acknowledgments: Joan Benach gratefully acknowledges the financial support by ICREA under the ICREA Academia programme. Conflicts of Interest: The authors declare no conflict of interest. Int. J. Environ. Res. Public Health 2022, 19, 12395 17 of 18 References 1. 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