Unemployment, Homelessness, and Other Societal Outcomes Among US Veterans With Schizophrenia Relapse: A Retrospective Cohort Study

Prim Care Companion CNS Disord 2022;24(5):21m03173

To cite: Lin D, Kim H, Wada K, et al. Unemployment, homelessness, and other societal outcomes among US veterans with schizophrenia relapse: a retrospective cohort study. Prim Care Companion CNS Disord. 2022;24(5):21m03173.
To share: https://doi.org/10.4088/PCC.21m03173

© 2022 Physicians Postgraduate Press, Inc.

^aJanssen Scientific Affairs, LLC, Titusville, New Jersey
^bIQVIA, Durham, North Carolina
^cClinical Epidemiology Program, White River Junction VA Medical Center, White River Junction, Vermont
*Corresponding author: Dee Lin, PharmD, MS, 1125 Trenton Harbourton Rd, Titusville, NJ 08560 ([email protected]).

Schizophrenia is a debilitating and severe mental health disorder, that according to the Global Burden of Disease Study, affects approximately 21 million people worldwide, including more than 1 million people in the United States.^1,2 The prevalence of schizophrenia, as well as other mental health disorders, is particularly high among US veterans. Of the 4 million US veterans evaluated in 2010 and 2011, approximately 164,000 were reported to have serious mental illness such as schizophrenia and bipolar disorder.³

Relapse in schizophrenia is common and characterized by acute psychotic exacerbation; relapse has been associated with disease progression, poorer response to treatment, and worsening of clinical symptoms.^4–7 Relapse has a detrimental impact on patients, caregivers, society, and health care systems.⁶ Reported relapse rates in schizophrenia ranged from 41% to 79% over a period of 12 months after treatment discontinuation^5,8–12; the wide range reflects inconsistent definitions of relapse across the studies.⁶ A US-based claims database study using data from 1997 to 2010 suggests that patients with schizophrenia had an average of 9 relapse episodes over 5.5 years.¹³ Key drivers of relapse include poor treatment adherence, chronic nature of schizophrenia, inappropriate treatment leading to nonadherence (eg, an increased dose of medication prescribed to prevent relapse may increase the side effects, which can result in nonadherence), psychological stress (such as traumatic experience and social isolation), and substance abuse.^5,14–17 It has been estimated that 1 in 5 patients will have poorer long-term outcomes following relapse¹⁸ and that only 1 in 7 will achieve long-term recovery.¹⁹ Furthermore, 1 episode of relapse has been identified as an important predictor of subsequent relapse.²⁰

Relapse leads to increased socioeconomic burden to the patients, their families, and society.^4–7 For example, a physician and patient survey study²¹ reported that having a relapse in the past 12 months was associated with homelessness, unemployment, history of incarceration, challenges in maintaining employment, impairment in work ability, inability to live independently, and poor quality of life. A systematic literature review²² of 16 studies estimated that the excess health care cost of relapse in the United States ranges from $6,033 to $32,753. Relapse episodes most often lead to emergency department (ED) visits and hospitalizations,²³ which are generally the largest contributors to the economic burden.²² Furthermore, costs associated with treatments received after relapse may account for the largest proportion of treatment costs associated with schizophrenia.¹⁴ Despite these previous studies on economic burden of schizophrenia and its relapse, the literature describing the non–health care societal burden of schizophrenia remains sparse.

The aim of this study was to evaluate societal outcomes such as unemployment, divorce, homelessness, incarceration, and premature death among veterans with schizophrenia with a history of relapse who receive care within the US Veterans Health Administration (VHA) system, wherein the prevalence of schizophrenia is high. This study will fill the existing gap in the literature on the impact of schizophrenia relapse outside of clinical and economic burden and provides a unique opportunity to identify areas for improvement with respect to social determinants of health, particularly in the US VHA population.

METHODS

Data Source

The VHA is the largest integrated health care system in the United States, providing comprehensive health care services to over 9 million veterans.²⁴ For this study, extracted from the integrated database of the VHA Corporate Data Warehouse (CDW). The VHA CDW contains medical records of inpatient, outpatient, and ED visits of veterans as well as demographic and mortality information collected from multiple VHA and non-VHA sources including Medicare Vital Status and the National Death Index. CDW data are updated daily. Data for employment, marital, housing, and incarceration statuses were obtained through linkage to the Veterans Benefits Administration Corporate Database, which is updated biannually. All study procedures were carried out in compliance with federal and institutional ethical guidelines. The Veterans Affairs Central Institutional Review Board (IRB; Study ID:1478231–1) provided approval for this study on December 17, 2019. The requirement to obtain informed consent from study participants was waived. The IRB deemed this study to involve no more than a minimal risk to the privacy of individuals. Data used in the study were deidentified, all analyses were conducted within the Veterans Affairs (VA) system, and only aggregated results were provided to non-VA individuals involved with this study.

Study Design

This was a retrospective cohort study using VHA data from January 1, 2013, to September 30, 2019 (study period). The study included veterans receiving care within the VHA who had ≥ 2 diagnoses of schizophrenia, schizotypal disorder, or schizoaffective disorders (ICD-9-CM 295.xx, ICD-10-CM F20.x, F21, or F25.x) on different days during the study period. At least 1 of these diagnoses was required to be in the patient selection window of January 1, 2014, through September 30, 2019, to allow for a 12-month preindex period and variable follow-up period. The index date was the date of the earliest diagnosis observed during the selection window. Two schizophrenia cohorts, the relapse and nonrelapse cohorts, were created based on a history of schizophrenia-related relapse, defined as an inpatient stay or ED visit with 1 of the schizophrenia diagnoses in any position in the preindex period. The complete inclusion and exclusion criteria are provided in Figure 1.

Baseline Measures

Patient sociodemographic and baseline clinical characteristics from the 12-month preindex period were reported. Clinical characteristics included the Charlson Comorbidity Index (CCI),²⁵ mental health and substance use comorbidities, and the self-reported Patient Health Questionnaire-2 (PHQ-2)²⁶ score.

Study Outcomes

The frequency of unemployment, divorce, homelessness, incarceration, and premature death (defined as death before aged 80 years²⁷), based on the most recent nonmissing data during the study period, was reported for each cohort. The number and proportion of veterans with missing data for each of these variables were reported as a separate category. The frequency of death and relapse, as well as time from index to relapse, was reported based on the variable follow-up period.

Statistical Analysis

Veterans in the relapse cohort were matched 1:1 with veterans in the nonrelapse cohort using propensity scores (PS); greedy nearest neighbor matching without replacement (caliper of 0.01) was used. The PS model included age category, sex, race, geographic region of residence, urban or rural residence, index year, and CCI. The matched cohorts were considered well-balanced for a given variable if the absolute standardized mean difference (SMD) was < 0.1 between the cohorts.

For descriptive analyses, categorical measures were reported as frequency and percentage, and continuous variables were described as mean, standard deviation (SD), first quartile (Q1), median, third quartile (Q3), minimum, and maximum. The matched cohorts were compared using SMD, with any value ≥ 0.1 considered statistically meaningful. Data were analyzed using SAS version 9.4 (SAS Institute Inc, Cary, North Carolina).

RESULTS

Baseline Demographic and Clinical Characteristics

A total of 119,343 veterans with schizophrenia met the selection criteria, resulting in 16,866 patients in the relapse cohort and 102,477 in the nonrelapse cohort prior to matching (Figure 1). After PS matching, 16,862 veterans remained in each cohort.

The matched cohorts were well-balanced in terms of demographic characteristics (Table 1). Nearly all veterans were male (91.9% of the relapse cohort, 92.1% of the nonrelapse cohort); the median age was 58–59 years in both cohorts. The majority of veterans were White (57.3% of the relapse cohort and 57.5% of the nonrelapse cohort), and most of the remaining veterans were Black (35.3% for both cohorts, all SMD < 0.1). CCI scores were also similar between the matched cohorts, with a median score of 2 (SMD = 0.05). The key differences between the cohorts were observed in baseline comorbidities, with the relapse cohort having a higher frequency of both non–mental health and mental health comorbidities compared to the nonrelapse cohort, including hypertension (56.4% vs 36.0%, SMD = 0.42), hyperlipidemia (44.6% vs 28.5%, SMD = 0.34), and liver disease (10.0% vs 4.2%, SMD = 0.23) (Table 1). Furthermore, compared to the nonrelapse cohort, the relapse cohort had a higher frequency of substance use disorder (67.4% vs 43.5%, SMD = 0.50), posttraumatic stress disorder (18.3% vs 15.3%, SMD = 0.08), and anxiety disorders (15.5% vs 9.0%, SMD = 0.20). Suicidal ideation was also observed in 19.7% of the relapse cohort compared to 2.2% in the nonrelapse cohort (SMD = 0.58). The frequency of suicide attempt was low in both cohorts but numerically higher for the relapse cohort (2.2% vs 0.4%, SMD = 0.16). PHQ-2 scores were similar with a mean of 1.1 in the relapse cohort compared to 1.0 in the nonrelapse cohort (SMD = 0.09).

Relapse During Follow-Up

The mean follow-up was 4.7 years for the relapse cohort and 4.9 years for the nonrelapse cohort (SMD = 0.10). The frequency of relapse during the follow-up period were significantly higher for the relapse cohort compared to the nonrelapse cohort (76.8% vs 46.7%, respectively, SMD = 0.65). The mean time from index to the first relapse during follow-up was also shorter in the relapse cohort (12.3 months vs 19.9 months for the nonrelapse cohort, SMD = 0.43) (Table 2).

Non–Health Care Societal Burden

A higher proportion of the relapse cohort experienced unemployment (75.4% vs 71.4%), divorce (35.6% vs 33.7%), homelessness (38.9% vs 23.7%), and incarceration (0.6% vs 0.4%) (all SMD > 0.1, Table 3, Figure 2). Similarly, a higher proportion of the relapse cohort died during the follow-up period compared to the nonrelapse cohort (26.8% vs 19.5%, SMD = 0.17) (Table 2). The proportion of veterans considered to have died prematurely was also higher for the relapse cohort (23.3%) compared to the nonrelapse cohort (16.9%; SMD = 0.16).

DISCUSSION

Our study included 16,862 veterans in each cohort (veterans with schizophrenia with and without a prior schizophrenia-related relapse). Nearly all veterans were male (92.0%), more than half of veterans were White (57.0%), and the median age was 58–59 years. In the relapse cohort, 67.4% and 42.0% of veterans had a history of substance use disorder and non-schizophrenia mental health disorder, respectively, compared to 43.5% and 23.8% in the matched nonrelapse cohort (both SMD > 0.1). The relapse cohort had a higher frequency of unemployment (75.4% vs 71.4%), divorce (35.6% vs 33.7%), homelessness (38.9% vs 23.7%), incarceration (0.6% vs 0.4%), and premature death (23.3% vs 16.9%) compared to the nonrelapse cohort (all SMD > 0.1).

The results of this study fill an important knowledge gap on the frequency of non–health care, societal outcomes among US veterans with schizophrenia with a history of relapse who receive care within the VHA. An early phase of this study shed light on the increased societal burden of schizophrenia²⁸; therefore, in the present study, we chose to evaluate the additional burden of relapse, which is common among patients with schizophrenia.⁵

Our findings suggest that veterans who had a prior schizophrenia-related relapse have a higher frequency of unemployment, divorce, homelessness, and incarceration. These findings are consistent with those reported in a prior cross-sectional survey of psychiatrists and their patients with schizophrenia in the United States,²¹ which reported an increased likelihood of negative societal outcomes among patients with relapse(s) in the past 12 months compared to those with no relapse. For example, patients with relapse had a 67% lower likelihood of being employed compared to those without relapse (risk ratio = 0.3, P = .001), and patients with 3 prior relapses or more were 24 times more likely to lose their homes compared to those without relapse (odds ratio = 23.6, P < .001).²¹ Furthermore, our study found that 77% of the relapse cohort experienced a subsequent relapse during follow-up compared to 47% of veterans without prior relapse. It is important to note that our study did not investigate treatment utilization or compliance. Our findings are consistent with the literature reporting a high frequency of relapse among those who had relapse at least once.²⁰

Veterans with prior relapse in our study also had more comorbidities, including mental health conditions, compared to their nonrelapse counterparts. Although balanced on overall CCI score from PS matching, veterans with relapse had a higher frequency of not only mental health comorbidities including trauma and stressor-related disorders and anxiety disorders, but also hypertension, hyperlipidemia, obesity, and chronic obstructive pulmonary disease. Moreover, a higher frequency of liver disease and hepatitis was observed among patients with a history of relapse. Additionally, a large proportion of veterans (67% of the relapse cohort and 44% of the nonrelapse cohort) included in our study had experienced substance use disorder. Similar findings were observed in a large prospective observational study of the US Schizophrenia Care and Assessment Program²⁰ in which patients who had not experienced relapse prior to or during the study period were less likely to have comorbid substance use disorder. This high rate of substance use disorder has been frequently reported among the US veteran population, and a comparison of schizophrenia patients to nonschizophrenia controls showed nearly 20% higher frequency of substance use disorder in those with schizophrenia.²⁸

Suicidal ideation in the relapse cohort was high (1 in 5 veterans)—10 times more than that in the nonrelapse cohort (2%). Although rare in the study population and likely underdocumented in the database, suspected suicide attempts were 5 times more common in the relapse cohort (more than 2% of the relapse cohort). These findings are consistent with several global studies^{4,17,20,29–31} that have identified a strong correlation between relapse and suicide ideation and/or attempt. Another UK-based study revealed that patients with relapse had 4 times the odds of suicide attempt compared to those without relapse.⁴ Similarly, a US cross-sectional study²¹ conducted in 2019 suggested an increasing trend in the mean number of suicide attempts with increasing number of relapses. To that end, some studies^20,23 have also considered self-harm, suicide attempts, and suicide ideation as indicators of relapse, substantiating their correlation.

Strengths of this study include use of the most recent VHA data, which provided large sample size and long-term follow-up; this enabled the comprehensive evaluation of non–health care societal burden of schizophrenia relapse in recent years. Further, this study provides valuable insights on societal outcomes in a patient population with more severe schizophrenia who have a higher risk of medical comorbidities and mental health disorders,^32,33 a population often understudied in the literature. Several limitations of this study should be noted. First, the VHA population differs considerably from the general US population; for example, the population in this study was 92% male. While the characteristics of the veterans in our study are consistent with other studies on schizophrenia leveraging the VHA data,^34,35 the generalizability of our findings to a broader population is limited. Second, our study did not investigate treatment utilization or compliance. This information in particular would help interpret our finding on the high frequency of relapse during the follow-up period for both cohorts. Third, because a cross-sectional approach was used in examining societal outcomes across the full study period, no temporality was applied between the exposure (relapse) and the outcomes of interest. Therefore, it is important to note that the nonrelapse cohort may have had a relapse during follow-up, which occurred prior to their most recent societal burden measure captured in this study. Finally, although consistent with prior real-world studies,⁶ our study defined an episode of relapse as an inpatient stay or ED visit with a diagnosis code for schizophrenia in any position, as opposed to a confirmed relapse based on clinical measures and noted in patient medical records.

CONCLUSION

Among a US veteran population, schizophrenia-related relapse was associated with significantly increased frequency of unemployment, divorce, homelessness, and incarceration, as well as increased risk of premature death and subsequent relapse. Preventing relapse, managing comorbid mental health and substance use conditions, and providing services to help with employment and housing for this vulnerable population may improve societal and clinical outcomes for patients.

Submitted: October 14, 2021; accepted March 1, 2022.
Published online: September 13, 2022.
Funding/support: This study was funded by Janssen Scientific Affairs, LLC.
Role of the sponsor: Janssen participated in study concept design, protocol development, interpretation of the results, and review of the draft manuscript.
Relevant financial relationships: Dr Lin is an employee of Janssen Scientific Affairs, LLC, and holds stock in Johnson & Johnson. Mss Kim and Wada were employees of IQVIA at the time of the study, and IQVIA was paid by Janssen to conduct the research study. Mss Aboumrad and Zwain and Mr Powell are employees of the VA, and the VA was paid by IQVIA to conduct data analysis. Ms Benson is an employee of Janssen Scientific Affairs, LLC, and a stockholder of Johnson & Johnson. Ms Near is an employee of IQVIA, and IQVIA was paid by Janssen to conduct the research study.
Previous presentation: Presented at the College of Psychiatric and Neurologic Pharmacists (CPNP) 2021 Annual Meeting; April 19–23, 2021; virtual meeting.

Clinical Points

• The impact of schizophrenia relapse on societal burden, outside of clinical and economic burden, is substantial.
• Schizophrenia-related relapse was associated with significantly increased frequency of unemployment, divorce, homelessness, and incarceration, as well as increased risk of premature death and subsequent relapse.
• Clinically preventing relapse and managing comorbid mental health and substance abuse conditions, while addressing social determinants of health, may improve societal and clinical outcomes for patients.