Economic burden of treatment-resistant depression among veterans in the United States.

OBJECTIVE: Evidence is limited on the economic burden associated with treatment-resistant depression (TRD) among US veterans. We evaluated the economic burden among patients with major depressive disorder (MDD) with and without TRD, and those without MDD in the Veterans Health Administration (VHA). METHODS: Three cohorts were identified using VHA claims data (01APR2014-31MAR2018). Patients with MDD (aged ≥18) who failed ≥2 antidepressant treatments of adequate dose and duration were defined as having TRD; patients with MDD not meeting this criterion constituted the non-TRD MDD cohort (index: first antidepressant claim). The non-MDD cohort included those without MDD diagnosis (index: randomly assigned). Patients with psychosis, schizophrenia, manic/bipolar disorder, or dementia in the 6-month pre-index period were excluded. Patients with non-TRD MDD and non-MDD were matched 1:1 to patients with TRD based on demographic characteristics (age, gender, race, index year). Health care resource utilization (HRU) and costs were analyzed during the post-index period using a negative binomial model and ordinary least squares regression model, respectively. RESULTS: After 1:1 exact matching, 10,449 patients were included in each cohort (mean age: 48.9 years). Patients with TRD had higher per patient per year (PPPY) HRU than non-TRD MDD (all-cause inpatient visits: incidence rate ratio [IRR]: 1.70 [95% confidence interval: 1.57-1.83]) and non-MDD (IRR: 5.04 [95% confidence interval: 4.51-5.63]), and incurred higher total all-cause health care costs PPPY than non-TRD MDD (mean difference: $5,906) and non-MDD (mean difference: $11,873; all p<.0001). CONCLUSION: Among US veterans, TRD poses a significant incremental economic burden relative to non-TRD MDD and non-MDD.

The prospective economic impact of once monthly paliperidone palmitate versus oral atypical antipsychotics in Medicaid patients with schizophrenia.

OBJECTIVES: Multiple real-world studies have reported potential cost savings associated with second-generation antipsychotic long-acting injectable therapies (SGA-LAIs), including once monthly paliperidone palmitate (PP1M). Yet, only about 12% of Medicaid patients with schizophrenia initiate SGA-LAIs, with poor adherence contributing to frequent relapse among patients on oral atypical antipsychotics (OAAs). The objective of this study was to project the economic impact when an incremental proportion of non-adherent patients with a recent relapse switched from OAAs to PP1M. METHODS: A 12 month decision-tree model was developed from a Medicaid payers' perspective. The target population was non-adherent OAA patients with a recent relapse. At equal adherence, risk of relapse was equal between PP1M and OAAs, and OAA patients remained non-adherent until treatment switch. Outcomes included number of relapses, relapse costs and pharmacy costs. RESULTS: Based on a hypothetical health plan of 1 million members, 3037 schizophrenia patients were non-adherent on OAAs with a recent relapse. Compared to continuing OAAs, switching 5% of patients (n = 152) to PP1M resulted in net schizophrenia-related cost savings of $674,975 at a plan level, $4445 per patient switched per year and $0.0562 per member per month, with a total of 92 avoided relapses over 12 months. Total annual plan level schizophrenia-related costs were $114.1 M when all patients switched to PP1M before any subsequent relapse (n = 3037), $123.4 M when patients switched to PP1M after a first subsequent relapse (n = 2631), and $127.6 M when all patients continued OAAs. Switching all patients to PP1M before any subsequent relapse averted 917 relapses, at a lower cost per patient switched ($37,559) compared to switching after a first subsequent relapse ($45,089) or continuing OAAs ($42,005). CONCLUSION: Over 12 months, pharmacy costs associated with switching patients from OAAs to PP1M were offset by reduced relapse rates and schizophrenia-related healthcare expenditures, with earlier use of PP1M projected to generate greater cost savings.

A comparison of treatment patterns, healthcare resource utilization, and costs among young adult Medicaid beneficiaries with schizophrenia treated with paliperidone palmitate or oral atypical antipsychotics in the US.

BACKGROUND: Much of the burden associated with schizophrenia is attributed to its early onset and chronic nature. Treatment with once monthly paliperidone palmitate (PP1M) is associated with lower healthcare utilization and better adherence as compared to oral atypical antipsychotics (OAAs). This study aimed to evaluate real-world effectiveness of PP1M and OAA therapies among US-based adult Medicaid patients with schizophrenia, overall and among young adults aged 18-35 years. METHODS: Adult patients with a diagnosis of schizophrenia and at least two claims for PP1M or OAA between January 1, 2010 and December 31, 2014 were selected from the IBM Watson Health MarketScan Medicaid Database. Treatment patterns and healthcare resource utilization and costs were compared between PP1M and OAA treatment groups following inverse probability of treatment (IPT) weighting to adjust for potential differences. Utilization and cost outcomes were estimated using OLS and weighted Poisson regression models. RESULTS: After IPT weighting, the young adult PP1M and OAA cohorts were comprised of 3,095 and 3,155 patients, respectively. PP1M patients had a higher duration of continuous treatment exposure (168.2 vs 132.5 days, p = .004) and better adherence on the index medication (proportion of days covered ≥80%: 19.0% vs 17.1%, p < .049). Young adults treated with PP1M were 37% less likely to have an all-cause inpatient admission (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.53-0.74) and 33% less likely to have an ER visit (OR = 0.67, 95% CI = 0.55-0.81) compared to OAA young adult patients, but 27% more likely to have an all-cause outpatient office visit (OR = 1.27, 95% CI = 1.02-1.56). PP1M patients incurred significantly lower medical costs as compared to OAA patients. CONCLUSIONS: Medicaid patients with schizophrenia treated with PP1M have higher medication adherence and have fewer hospitalizations as compared to patients treated with OAAs. PP1M may lead to reduced healthcare utilization and improved clinical outcomes.

Understanding healthcare burden and treatment patterns among young adults with schizophrenia.

BACKGROUND: Schizophrenia is a serious public health problem that affects ∼1% of the US population. AIMS: To examine treatment patterns and evaluate healthcare resource utilization (HRU) and costs among young adults (18-35 years) with schizophrenia who were early in the disease. MATERIALS AND METHODS: Patients aged 18-64 years with ≥2 schizophrenia diagnoses in the identification period (January 1, 2012-September 30, 2015) and continuous enrollment for ≥12 months pre- and post-index date were identified from the OptumInsight Clinformatics DataMart. Demographics, clinical characteristics, HRU, costs, and treatment patterns were compared between schizophrenia and non-schizophrenia "controls" cohorts and between young (18-35 years) and older adults (36-64 years) with schizophrenia. RESULTS: Among 9,889 schizophrenia patients, 23.70% were young adults (aged 18-35), had higher all-cause per-patient-per-year (PPPY) costs ($22,338 vs $7,332; p < .0001), higher inpatient costs ($8,857 vs $1,289; p < .0001), and longer inpatient length-of-stay (LOS) (5.0 vs 0.4 days, p < .0001; adjusted incidence rate ratio [aIRR] = 12.8; 95% confidence interval [CI] = 11.5-14.3) than controls. Among young adults with schizophrenia, there were more mental-health-related and fewer non-mental-health-related diagnoses compared to older adults with schizophrenia; 63.40% were male. Young adults with schizophrenia incurred higher inpatient costs ($15,692 vs $10,274; p < .0001) and longer inpatient LOS (9.6 vs 5.9 days, p < .0001; aIRR = 1.6; 95% CI = 1.4-1.8) compared to older adults with schizophrenia. A substantial proportion of patients were treated with oral antipsychotics vs long-acting injectables in both cohorts (young adults: 98.72% vs 9.71%; older adults: 98.10% vs 13.31%). LIMITATIONS: Claims data are collected for payment and not research. The presence of a prescription claim does not indicate medication was consumed or taken as prescribed. CONCLUSIONS: The economic burden for schizophrenia patients is substantial, especially among young adults. Based on this analysis, further research is warranted to better understand the association between adherent treatment patterns earlier in the disease and long-term health outcomes among patients with schizophrenia.

A systematic literature review of the clinical and health economic burden of schizophrenia in privately insured patients in the United States.

PURPOSE: The aim of this study was to conduct a systematic literature review on the burden of schizophrenia in privately insured US patients. MATERIALS AND METHODS: A systematic literature review of English language peer-reviewed journal articles of observational studies published from 2006 to 2016 was conducted using EMBASE/MEDLINE databases. Abstracts covering substantial numbers of patients with schizophrenia or schizoaffective disorder (i.e., N ≥ 100) were included for full-text review. Articles that did not clearly specify private insurance types were excluded. RESULTS: A total of 25 studies were reviewed; 10 included only privately insured patients; and 15 included a mix of different types of insurance. The review of the clinical burden of schizophrenia revealed the following: compared to patients with no mental disorders, those with schizophrenia had significantly increased odds of systemic disorders and both alcohol and substance abuse. Antipsychotic (AP) adherence was low, ranging from 31.5% to 68.7%. The medication possession ratio for AP adherence ranged from 0.22 to 0.73. The review of the health economic burden of schizophrenia revealed the following: patients with a recent (vs. chronic) diagnosis of schizophrenia had significantly higher frequencies of emergency department visits and hospitalizations and greater length of stay (LOS) and total annual per-capita costs. Mean all-cause hospitalizations and LOS decreased significantly after (vs. before) initiating long-acting injectable APs (LAIs). Patients also had significantly decreased mean all-cause, and schizophrenia-related, hospitalization costs after initiating LAIs. Total direct per-capita costs of care (but not pharmacy costs) for patients who were nonadherent to their oral APs within the first 90 days of their index event were significantly higher (vs. early adherent patients). Despite these potential benefits, only 0.25%-13.1% of patients were treated with LAIs across all studies. CONCLUSION: Privately insured US patients with schizophrenia experience a substantial clinical and health economic burden related to comorbidities, acute care needs, nonadherence, and polypharmacy and have relatively low use of LAIs. Further study is warranted to understand prescribing patterns and clinical policies related to this patient population.

Prospective Service Use and Health Care Costs of Medicaid Beneficiaries with Treatment-Resistant Depression.

BACKGROUND: Although the clinical and health economic characteristics of commercially insured adults with treatment-resistant depression (TRD) have been well characterized, little is known about TRD in the Medicaid population. OBJECTIVE: To describe clinical and health economic characteristics of adult Medicaid beneficiaries with TRD. METHODS: Retrospective longitudinal cohort analyses were performed with Truven Health MarketScan Medicaid Database (2008-2014), focusing on adults with major depressive disorder (MDD) following an index antidepressant prescription. TRD was operationally defined as starting a third treatment regimen after 2 adequate regimens of antidepressants or augmentation therapy within 12 months of an index antidepressant prescription. Among patients with and without TRD, percentages with inpatient admissions, emergency department visits, and outpatient visits (all cause, mental health related, and depression related) were determined. Logistic regression models were used to examine associations between TRD status and use of inpatient, outpatient, and emergency services. Separate analyses were performed for the first and second year after the index antidepressant prescription. RESULTS: Approximately one quarter (25.9%) of pharmacologically treated adults with MDD met criteria for TRD. In relation to MDD patients without TRD, patients with TRD were proportionately more likely to be older, male, and white. Compared with MDD patients without TRD, patients with TRD were also significantly more likely to receive inpatient care for any cause (31.0% vs. 21.6%; P < 0.001), a mental health-related reason (12.7% vs. 7.6%; P < 0.001), or depression (10.1% vs. 6.1%; P < 0.001) during the first year following their index antidepressant prescription. Over the second follow-up year, patients with TRD continued to be more likely than patients without TRD to receive inpatient care for any reason (26.7% vs. 19.5%; P < 0.001), a mental health-related reason (5.6% vs. 2.7%; P < 0.001), and depression (3.7% vs. 1.7%; P < 0.001). The mean health care costs of patients with TRD were also significantly higher than the costs of patients without TRD during the first year ($18,982 [SD ± $35,276] vs. $11,642 [SD ± $29,203]) and second year ($17,997 [SD ± $34,146] vs. $10,325 [SD ± $28,224]) following the index antidepressant prescription. CONCLUSIONS: In the U.S. Medicaid program, adults with TRD have substantially and persistently higher health care costs than their counterparts who do not meet criteria for TRD. The service use and health care cost patterns of patients with TRD in the Medicaid program highlight challenges of developing interventions and care coordination strategies to meet their complex clinical needs. DISCLOSURES: This project was sponsored by Janssen Scientific Affairs. Olfson received a grant from Janssen Scientific Affairs through Columbia University Medical Center. Amos and Benson are employees of Janssen Scientific Affairs. Marcus was paid by Janssen Scientific Affairs to provide consulting support for this study and reports fees from Sunovion Pharmaceuticals and Alkermes outside of this study. McRae was a fellow affiliated with Janssen Scientific Affairs during the development of this research and manuscript. Study concept and design were contributed by Amos, Olfson, Marcus, Benson, and McRae. Data analysis was performed by all the authors. The manuscript was primarily written by Olfson, along with the other authors, and revised by McRae, Benson, Amos, Marcus, and Olfson. A different data cut from the same database was presented previously at the 2017 Annual Meeting of the International Society for Pharmacoeconomics and Outcomes Research; May 20-24, 2017; Boston, MA; and the 2017 AcademyHealth Annual Research Meeting; June 25-27, 2017; New Orleans, LA.

Direct and Indirect Cost Burden and Change of Employment Status in Treatment-Resistant Depression: A Matched-Cohort Study Using a US Commercial Claims Database.

BACKGROUND: Treatment-resistant depression (TRD) poses a substantial burden to health care payers including employers, costing an estimated $29 billion-$48 billion yearly in the United States. Furthermore, variation of burden across increasing levels of resistance and the potential impact of TRD on employment status remain largely unexplored. OBJECTIVE: To evaluate health care resource utilization (HRU) and costs, work loss, indirect costs, and employment status change in TRD. METHODS: A claims-based algorithm identified adults with TRD from a US claims database of privately insured employees and dependents (January 2010-March 2015). TRD patients were matched 1:1 on demographics to patients with major depressive disorder (MDD) (non-TRD MDD) and without MDD (non-MDD), who were identified using ICD-9-CM codes. Costs, HRU, and employment status change were compared over 2 years following the first antidepressant (randomly imputed date for non-MDD), adjusting for baseline comorbidity index and costs. RESULTS: TRD patients (N = 6,411) had more HRU than either matched control cohort, translating into higher per patient per year (PPPY) health care costs: $6,709 and $9,917 more than non-TRD MDD and non-MDD patients, respectively (P < .001 for both). TRD patients with work loss data (N = 1,908) had 35.8 work loss days PPPY (1.7 and 6.2 times the work loss rate in non-TRD MDD and non-MDD patients, respectively). Work loss-related costs in TRD patients were $1,811 higher than non-TRD MDD and $3,460 higher than in non-MDD patients (P < .001). TRD patients had 1.3-1.4 times the rate of employment status change versus control cohorts (all P < .05). CONCLUSIONS: TRD, even compared to MDD, poses a significant direct and indirect cost burden to US employers and may be associated with higher rates of employment status change.

Treatment persistence and hospitalization rates among patients with schizophrenia: a quasi-experiment to evaluate a patient information program.

OBJECTIVE: The effective treatment of schizophrenia requires continuous antipsychotic maintenance therapy. However, poor persistence with treatment is common among patients with schizophrenia. The objective of this study was to compare persistence and hospitalization rates among patients with schizophrenia treated with long-acting injectable (LAI) antipsychotics (i.e. paliperidone palmitate and risperidone) and enrolled in a patient information program (program cohort) with patients treated with oral antipsychotics (OAs) who were not enrolled in a patient information program (nonprogram cohort). RESEARCH DESIGN AND METHODS: Using a quasi-experimental design, data from chart reviews (for program patients) and Medicaid claims (for nonprogram patients) was analyzed. Patients were eligible if they had ≥12 months of pre-index data, ≥6 months of post-index data, and no hospitalization at index. MAIN OUTCOME MEASURES: Persistence and hospitalization rates were assessed at 6 months post-index. Propensity score matching was used to control for observed differences in demographics and baseline clinical characteristics. Odds ratios (ORs) were calculated using generalized estimating equation models and adjusted for matched pairs and propensity score. RESULTS: A total of 102 program patients were matched to 408 nonprogram patients with similar baseline characteristics. Adjusted ORs indicated that the persistence rate at 6 months was significantly higher for the program cohort (88.2%) versus the nonprogram cohort (43.9%; OR: 9.70; P < .0001). The 6 month post-index hospitalization rate for the program cohort (14.7%) was significantly lower versus the nonprogram cohort after adjustments (22.5%; OR: 0.55; P = 0.0321). LIMITATIONS: The data for the program and nonprogram patients were from two different and independent data sources (healthcare claims and chart reviews, respectively). Results were based on a relatively small number of program LAI patients. CONCLUSION: Program patients treated with LAI antipsychotics had higher persistence rates and significantly lower adjusted hospitalization rates compared with nonprogram patients treated with OAs.

Healthcare costs of urinary tract infections and genital mycotic infections among patients with type 2 diabetes mellitus initiated on canagliflozin: a retrospective cohort study.

OBJECTIVE: To assess the economic impact of urinary tract infections (UTIs) and genital mycotic infections (GMIs) among patients with type 2 diabetes mellitus (T2DM) initiated on canagliflozin. METHODS: Administrative claims data from April 2013 through June 2014 MarketScan® databases were extracted. Adults with ≥1 claim for canagliflozin, T2DM diagnosis, and ≥90 days enrollment before and after canagliflozin initiation were propensity score matched to controls with T2DM initiated on other anti-hyperglycemic agents (AHAs). UTI and GMI healthcare costs were evaluated 90-days post-index and reported as cohort means. RESULTS: Rates of UTI claims 90 days post-index were similar in patients receiving canagliflozin for T2DM (n = 31,257) and matched controls (2.7% vs 2.8%, p = .677). More canagliflozin than control patients had GMI claims (1.2% vs 0.6%, p < .001) and antifungal utilization (5.3% vs 2.6%, p < .001). Mean post-index costs to treat UTIs were lower but not significantly different for canagliflozin patients vs matched controls ($27.61 vs $37.33, p = .150). GMI treatment costs were higher for the canagliflozin cohort ($3.68 vs $2.44, p = .041). Combined costs to treat either UTI and/or GMI averaged $31.29 per patient for the canagliflozin cohort v $39.77 for controls (p = .211). Rates and costs of UTIs and GMIs were higher for females than males, but the canagliflozin vs control trends observed for the overall sample were similar for both sexes. There were no significant cost differences between the canagliflozin and control cohorts among patients aged 18-64. Among patients aged 65 and above, GMI treatment costs were not significantly different, but costs to treat UTIs and either UTI and/or GMI were significantly lower for canagliflozin patients vs controls. CONCLUSIONS: In a real-world setting, the costs to payers of treating UTIs and GMIs are generally similar for patients with T2DM initiated on canagliflozin vs other AHAs.