Real-world assessment of treatment inertia in the management of patients treated for major depressive disorder in the USA.

Aim: Major depressive disorder (MDD) is a debilitating illness in which depressive symptoms may persist after treatment. Treatment inertia is the continued use of the same pharmacotherapy regimen when treatment goals are not met. This study assessed the frequency of treatment inertia among adult patients with MDD treated in a real-world setting. Patients & methods: This was a retrospective, observational study of patients with MDD identified in the Decision Resources Group Real World Evidence US Data Repository from January 2014 to June 2018. Patients (≥18 years) had an elevated Patient Health Questionnaire-9 (PHQ-9) score (≥5) following 8 weeks of stable baseline antidepressant use with/without mental-health outpatient therapy. Treatment inertia, modification and discontinuation were evaluated over a 16-week follow-up period (timeline based on the APA Practice Guidelines). The primary outcome was the proportion of MDD patients experiencing treatment inertia. Results: 2850 patients (median age, 55 years; 74% female) met the study criteria. Of these patients, 834 (29%) had study-defined treatment inertia, 1534 (54%) received treatment modification and 482 (17%) discontinued treatment. Use of mirtazapine (Odd ratio [OR]: 0.63; 95% confidence interval [CI]: 0.50-0.79), selective serotonin reuptake inhibitors (OR: 0.64; 95% CI: 0.54-0.75) or bupropion (OR: 0.71; 95% CI: 0.60-0.84) in the baseline period was associated with an increased likelihood of treatment modification versus not receiving treatment with these medications. Frequency of treatment inertia may differ among those who do not have a documented PHQ-9 score. Conclusion: Effective symptom management is critical for optimal outcomes in MDD. Results demonstrate that treatment inertia is common in MDD despite guidelines recommending treatment modification in patients not reaching remission.

How Much Better is Faster? Value Adjustments for Health-Improvement Sequences.

While the quality-adjusted life-year construct has advantages of simplicity and consistency, simplicity requires strong assumptions. In particular, standard assumptions result in health-state utility functions that are unrealistically linear and separable in risk and duration. Consequently, sequencing of a series of health improvements has no effect on the total value of the sequence because each increment is assessed independently of previous increments. Utility functions in nearly all other areas of applied economics are assumed to be nonlinear with diminishing marginal utility so it matters where an improvement occurs in a sequence. We construct a conceptual framework that that demonstrates how diminishing marginal utility for health improvements could affect preferences for different sequence patterns. Using this framework, we derive conditions for which the sum of conventional health-state utilities understates, overstates, or approximates the sequence-sensitive value of health improvements. These patterns suggest the direction and magnitude of possible adjustments to conventional value calculations. We provide numerical examples and identify recent studies whose results are consistent with the conceptual model.

Assessment of economic burden of fatigue in adults with multiple sclerosis: An analysis of US National Health and Wellness Survey data.

BACKGROUND: Fatigue, a common disabling symptom in multiple sclerosis (MS), is reported by the majority of patients. However, evidence on the economic burden of fatigue in MS by fatigue status is limited. This study aimed to evaluate the economic burden of fatigue, including healthcare resource utilization (HCRU), labor force participation, and Work Productivity and Activity Impairment (WPAI), among adults with relapsing-remitting MS (RRMS) by low fatigue (LF) vs high fatigue (HF) and compared with adults without MS. METHODS: This cross-sectional, retrospective, observational study included pooled data from the 2017 and 2019 US National Health and Wellness Survey. The RRMS sample included respondents aged ≥18 years who reported being diagnosed with MS by a healthcare provider (HCP) and reported having RRMS. Non-MS controls included respondents aged ≥18 years who did not report being diagnosed with MS by an HCP. Fatigue was measured using the Modified Fatigue Impact Scale-5 (MFIS-5). Outcomes included HCRU (HCP visits, emergency department visits, and hospitalizations in the past 12 months), labor force participation (yes vs no), WPAI (absenteeism, presenteeism, total work productivity impairment, and activity impairment), and annualized costs (direct medical, indirect, and total). Respondents with RRMS were propensity-score matched to non-MS controls (ratio 1:3). RRMS respondents were categorized as having LF (MFIS-5<15; RRMS+LF) and HF (MFIS-5≥15; RRMS+HF). Bivariate analysis compared matched non-MS controls, RRMS+LF, and RRMS+HF. Multivariable analyses were conducted among RRMS to evaluate associations between fatigue (continuous variable) and outcomes. RESULTS: Overall, 498 respondents with RRMS (RRMS+LF, n=375; RRMS+HF, n=123) and 1494 matched non-MS controls were included. RRMS+HF and RRMS+LF had more HCRU in the past 12 months than non-MS controls, whereas RRMS+HF had greater HCRU than RRMS+LF (all p<0.05). WPAI was also higher among RRMS+HF and RRMS+LF, compared with non-MS controls, as well as higher in RRMS+HF vs RRMS+LF (all p<0.001). RRMS+HF had significantly higher annualized direct medical costs than RRMS+LF and matched non-MS controls ($19,978 vs $10,656, p=0.007; vs $8,048, p<0.001). Among employed respondents, RRMS+HF and RRMS+LF had higher annualized indirect costs than non-MS controls, with RRMS+HF also having higher annualized indirect costs than RRMS+LF ($23,647 vs $13,738 vs $8,001; all p<0.01); total annualized costs were higher in RRMS+HF and RRMS+LF, compared with non-MS controls, as well as RRMS+HF vs RRMS+LF (all p<0.01). In multivariable models, fatigue was significantly and positively associated with the number of HCP visits in the past 12 months (p=0.002); not participating in the labor force (p<0.001); and absenteeism, presenteeism, total work productivity impairment, and activity impairment (all p<0.001). CONCLUSION: RRMS poses a substantial economic burden on patients and society, and this burden is disproportionately associated with HF.

Excess healthcare resource utilization and healthcare costs among privately and publicly insured patients with major depressive disorder and acute suicidal ideation or behavior in the United States.

BACKGROUND: This study assessed the healthcare resource utilization (HRU) and cost burden of patients with major depressive disorder (MDD) and acute suicidal ideation or behavior (SIB; MDSI) versus those with MDD without SIB and those without MDD. METHODS: Adults were selected from the MarketScan® Databases (10/2015-02/2020). The MDSI cohort received an MDD diagnosis within 6 months of a claim for acute SIB (index date). The index date was a random MDD claim in the MDD without SIB cohort and a random date in the non-MDD cohort. Patients had continuous eligibility ≥12 months pre- and ≥1 month post-index. HRU and costs were compared during 1- and 12-month post-index periods between MDSI and control cohorts matched 1:1 on demographics. RESULTS: The MDSI cohort included 73,242 patients (mean age 35 years, 60.6% female, 37.2% Medicaid coverage). At 1 month post-index, the MDSI cohort versus the MDD without SIB/non-MDD cohorts had 12.8/67.2 times more inpatient admissions and 3.3/8.9 times more emergency department visits; they had 2.9 times more outpatient visits versus the non-MDD cohort (all p < 0.001). The MDSI cohort had incremental mean healthcare costs of $5255 and $6674 per-patient-month versus the MDD without SIB and non-MDD cohorts (all p < 0.001); inpatient costs drove up to 89.5% of incremental costs. At 12 months post-index, HRU and costs remained higher in MDSI versus control cohorts. LIMITATIONS: SIB are underreported in claims; unobserved confounders may cause bias. CONCLUSIONS: MDSI is associated with substantial excess healthcare costs driven by inpatient costs, concentrated in the first month post-index, and persisting during the following year.

Economic Burden of Commercially Insured Patients With Major Depressive Disorder and Acute Suicidal Ideation or Behavior in the United States.

Objective: Suicidal ideation or behavior (SIB) is a symptom of major depressive disorder (MDD). This study evaluated health care resource utilization (HRU) and costs of commercially insured adults who had diagnosed MDD with acute SIB (MDSI).Methods: Adults with MDSI (index date: first SIB claim) and controls without MDD or suicide-related claims (random index date) were identified using International Classification of Diseases, Clinical Modification, 10th Revision codes in the OptumHealth Care Solutions, Inc. database (October 2014 to March 2017). Adults with < 12 months of plan enrollment pre-index and/or selected psychiatric comorbidities were excluded. MDSI and control cohorts were matched 1:1 on demographics and comorbidities. HRU and costs were compared between matched cohorts during up to 1 and 12 months post-index (inclusive) using regressions adjusted for baseline costs.Results: Among patients with MDSI (n = 1,576, mean age = 34 years, 55.6% female), most index events occurred in emergency department (ED; 50.7%) and inpatient (45.2%) settings. The MDSI cohort, compared with the control cohort within 1 and 12 months post-index, respectively, had 157.7 and 28.0 times more inpatient admissions, 16.4 and 5.4 times more ED visits, and 4.9 and 3.2 times more outpatient visits (all P < .01). Incremental health care costs per patient per month in the MDSI compared with the control cohort within 1 and 12 months were $7,839 and $2,757, respectively (both P values < .01). Inpatient and ED costs constituted 70.6% and 16.5% of the total incremental costs, respectively, within the first month of follow-up.Conclusions: Among commercially insured adults, MDSI was associated with significant economic burden; inpatient and ED services drove incremental costs of the condition. Further assessment of treatment options for this vulnerable patient population is warranted.

Characteristics and current standard of care among veterans with major depressive disorder in the United States: A real-world data analysis.

BACKGROUND: This study examined MDD treatment regimens received during the first observed and treated major depressive episode (MDE) among US veterans. METHODS: This retrospective study, conducted using the Veterans Health Administration (VHA) database, supplemented with Medicare Part A/B/D data, included adults with ≥1 MDD diagnosis (index date) between 10/1/2015-2/28/2017 and ≥1 line of therapy (LOT) within the first observed complete MDE. Patient baseline (6-month pre-index) characteristics and up to six LOTs received during the first observed and treated MDE were assessed. RESULTS: Of 40,240 veterans with MDD identified (mean age: 50.9 years, 83.9% male, 63.4% White, 88.6% non-Hispanic), hypertension (27.5%), hyperlipidemia (20.8%), and post-traumatic stress disorder (17.5%) were the most common baseline comorbidities. During the first observed and treated MDE, patients received a mean of 1.6 ± 1.0 LOTs, with 14.6% of patients receiving ≥3 LOTs. SSRI-monotherapy was the most commonly observed regimen in the first six LOTs, followed by SNRI-monotherapy in LOT 1 and antidepressants augmented by anticonvulsants in the remaining five LOTs. The antidepressant class of the previous LOT was commonly used in the subsequent LOT. SSRI-SSRI-SSRI was the most common LOT1-to-LOT3 sequencing pattern among patients receiving ≥3 LOTs. LIMITATIONS: The study findings are limited to data in the VHA database and may not be generalizable to the non-veteran US population. CONCLUSIONS: During the first observed and treated MDE, SSRI-monotherapy was the most common therapy in the first six LOTs. Cycling within SSRI class was the leading sequencing pattern of the first three LOTs among veterans who received ≥3 LOTs.

US budget impact analysis of esketamine nasal spray in major depressive disorder with acute suicidal ideation/behavior.

Background: Esketamine nasal spray plus an oral antidepressant is approved in adults with major depressive disorder with acute suicidal ideation or behavior (MDSI). Methods: A budget impact analysis from a US payer perspective was performed with a hypothetical 1-million-member plan, using pharmacy and medical costs associated with adding esketamine plus an oral antidepressant to usual care. Results: Estimated annual total healthcare costs of managing patients with MDSI increased from $32,988,247 without esketamine to $34,161,188 in Year 3 with esketamine (primarily due to medical costs). The per-member-per-month incremental costs were $0.02, $0.06 and $0.10 in Years 1, 2 and 3, respectively. Conclusion: Incorporation of esketamine results in a modest estimated impact on the annual budget over a 3-year time horizon.

Health care resource use, short-term disability days, and costs associated with states of persistence on antidepressant lines of therapy.

AIMS: To compare health care resource utilization (HCRU), short-term disability days, and costs between states of persistence on antidepressant lines of therapy after evidence of treatment-resistant depression (TRD). METHODS: Patients with major depressive disorder (MDD) were identified in the IBM MarketScan Commercial and Medicare Supplemental Databases (01/01/2013-03/04/2019), Multi-State Medicaid Database (01/01/2013-12/31/2018), and Health Productivity Management Database (01/01/2015-12/31/2018). The index date was the date of the first evidence of TRD during the first observed major depressive episode. The follow-up period was divided into 45-day increments and categorized into persistence states: (1) evaluation (first 45 days after evidence of TRD); (2) persistence on the early line after evidence of TRD; (3) persistence on a late line; and (4) non-persistence. HCRU, short-term disability days, and costs were compared between persistence states using multivariate generalized estimating equations. RESULTS: Among 10,053 patients with TRD, the evaluation state was associated with higher likelihood of all-cause inpatient admissions (odds ratio [OR; 95% confidence interval (CI)] = 1.79 [1.49, 2.14]), emergency department visits (OR [95% CI] = 1.23 [1.12, 1.34]), and outpatient visits (OR [95% CI] = 3.83 [3.51, 4.18]; all p < .001) versus persistence on the early-line therapy. This resulted in $374 higher mean PPPM all-cause health care costs (95% CI = 265, 470; p < .001) during evaluation versus persistence on the early line therapy. The evaluation state was associated with 89% more short-term disability days (OR [95% CI] = 1.89 [1.49, 2.57] and $212 higher mean PPPM short-term disability costs (95% CI = 64, 259) relative to persistence on the early line (both p < .001). Moreover, during persistence on a later line, mean PPPM all-cause health care costs were $141 higher (95% CI = 13, 242; p = .028) relative to the early line. LIMITATIONS: Medication may have been dispensed but not actually taken. CONCLUSIONS: Higher costs during the first 45 days after evidence of the presence of TRD and during persistence on a late line relative to persistence on the early-line therapy suggest there are benefits to using more effective treatments earlier.

Prevalence of Pre-existing Conditions Relevant for Adverse Events and Potential Drug-Drug Interactions Associated with Augmentation Therapies Among Patients with Treatment-Resistant Depression.

INTRODUCTION: Pre-existing conditions relevant for adverse events (AE) and the potential for drug-drug interactions (DDIs) may limit safe pharmacotherapeutic augmentation options for patients with major depressive disorder (MDD). This concern may be heightened among patients with treatment-resistant depression (TRD), who often have comorbid medical disorders. METHODS: Adults with MDD and ≥ 1 antidepressant claim within the first observed major depressive episode were identified in the MarketScan® Databases. Those initiating a new regimen after two regimens at adequate dose and duration were considered to have TRD. The index date was defined at TRD onset or on a random antidepressant claim among patients with non-TRD MDD. Pre-existing conditions 12 months pre-index and potential DDIs 3 months pre/post-index associated with specific non-antidepressant augmentation therapies, including atypical antipsychotics (APs), buspirone, psychostimulants, anticonvulsants, thyroid hormone, and lithium were compared between 1:1 matched TRD and non-TRD MDD cohorts. RESULTS: Overall, 3414 patients with TRD and non-TRD MDD (mean age 39.7 years, 69% female) were matched. Relative to non-TRD MDD, patients with TRD had 33% higher likelihood of ≥ 1 pre-existing condition relevant for AEs listed in product labels of non-antidepressant augmentation therapies (p < 0.001). Patients with TRD vs. non-TRD MDD had 12.9 and 6.4 times higher likelihood of ≥ 2 and ≥ 3 DDIs, respectively, based on their medication regimen (all p < 0.001). CONCLUSION: Pre-existing conditions relevant for listed AEs and potential DDIs limit safe augmentation options in MDD, particularly among patients with TRD. Payer prior authorization policies requiring several augmentation therapy trials to access novel treatments may complicate clinical management of this population.

Direct and Indirect Costs Among Caregivers of Patients With Major Depressive Disorder and Suicidal Ideation or Suicidal Attempt.

Objective: To compare direct and indirect costs among caregivers of patients with major depressive disorder (MDD) and suicidal ideation and/or suicide attempts (MDSI) versus caregivers of patients with MDD alone versus caregivers of patients without MDD or suicidal ideation and/or suicide attempts (controls).Methods: Cohorts were based on caregivers of adult patients with MDSI, MDD alone, and controls. Patients were identified by Workpartners employer database ICD-9/ICD-10 codes (January 2010 to July 2019) and were spouses or domestic partners of employees (caregivers). Twenty controls and 20 MDD-alone caregivers were matched to each MDSI caregiver on sex, age, and index year. All caregiver-patient pairs had 6 months pre/postindex information and met additional inclusion/exclusion criteria. Patient and caregiver medical and prescription claims and caregiver absenteeism (payment/time) were analyzed. Direct costs (medical, prescription) and indirect costs (absence payments by benefit type) were analyzed using separate, 2-part stepwise regression models and controlling for demographics, job-related variables, region, index year, and Charlson Comorbidity Index score.Results: 570 MDSI caregiver-patient pairs and 11,400 matched MDD-alone and control pairs were identified. MDSI and MDD-alone caregivers had higher medical costs compared with controls ($5,131 and $4,548 versus $3,885, respectively; P < .0001). Prescription costs were highest among MDSI caregivers, followed by MDD-alone and control caregivers ($1,852, $1,425, and $1,005, respectively; P < .001). MDSI caregivers had the highest total indirect costs. MDSI patient medical and prescription costs were highest, followed by MDD-alone and control patients.Conclusion: MDSI caregivers had significantly greater direct and indirect costs compared with MDD-alone and non-MDD caregivers.

The Prevalence and National Burden of Treatment-Resistant Depression and Major Depressive Disorder in the United States.

OBJECTIVE: Estimates of prevalence and burden of treatment-resistant depression (TRD) vary widely in the literature. This study evaluated the prevalence and burden of TRD and the share of TRD in the burden of medication-treated major depressive disorder (MDD) using the most commonly accepted definition of TRD and a novel bottom-up approach. METHODS: Prevalence and health care burden of TRD were estimated by synthetizing inputs across 4 similarly designed claims studies in adults covered by Medicare, Medicaid, commercial plans, and the US Veterans Health Administration (VHA). Productivity (absenteeism and presenteeism) and unemployment burden were estimated based on inputs from a study conducted with data from the Kantar National Health and Wellness Survey (NHWS; 2017). A targeted literature search for additional inputs was performed. A cost model was developed to estimate the burden of TRD and medication-treated DSM-5-defined MDD in the United States. Study outcomes were the 12-month prevalence of TRD and the annual health care, productivity, and unemployment burden of TRD and medication-treated MDD in the United States. RESULTS: The estimated 12-month prevalence of medication-treated MDD in the United States was 8.9 million adults, and 2.8 million (30.9%) had TRD. The total annual burden of medication-treated MDD among the US population was $92.7 billion, with $43.8 billion (47.2%) attributable to TRD. The share of TRD was 56.6% ($25.8 billion) of the health care burden, 47.7% ($8.7 billion) of the unemployment burden, and 32.2% ($9.3 billion) of the productivity burden of medication-treated MDD. CONCLUSIONS: TRD is associated with disproportionate health care costs and unemployment, suggesting potentially large economic and societal gains with effective management.

Cost-per-remitter with esketamine nasal spray versus standard of care for treatment-resistant depression.

Aim: Estimate the cost-per-remitter with esketamine nasal spray plus an oral antidepressant (ESK + oral AD) versus oral AD plus nasal placebo (oral AD + PBO) among patients with treatment-resistant depression. Patients & methods: An Excel-based model was developed to estimate the cost-per-remitter for ESK + oral AD versus oral AD + PBO over 52 weeks from multiple US payer perspectives. Clinical end points and cost inputs were derived from clinical trials and the literature, respectively. Results: Under the base-case scenario, the cost-per-remitter for ESK + oral AD and oral AD + PBO were as follows: Commercial: US$85,808 versus US$100,198; Medicaid: US$76,236 versus US$96,067; Veteran's Affairs: US$77,765 versus US$104,519; and Integrated Delivery Network: US$103,924 versus US$142,766. Conclusion: The findings suggest that ESK + oral AD is a cost-efficient alternative treatment for treatment-resistant depression compared with oral AD + PBO.

Lay abstract The US FDA recently approved esketamine nasal spray plus an oral antidepressant (AD) as a new treatment for adults with treatment-resistant depression. We developed an Excel-based model to understand whether esketamine + oral AD treatment offers better value for the money spent, compared with treatment with oral AD alone. We find that the higher annual costs of esketamine + oral AD treatment are more than offset by the better clinical outcomes achieved with this treatment. Specifically, in a given year, more people treated with esketamine + oral AD versus oral AD alone achieved and remained in remission, and as a result, they incurred fewer other medical costs.

Evaluation of biological and economic efficiency of the All Heifer, No Cow beef production system using a system dynamics model based on 6 yr of demonstration herd data.

Alternative management strategies with no cows and all heifers may improve biological and economic efficiency of beef production. The All Heifer, No Cow (AHNC) beef production system involves insemination of nulliparous heifers with female sex-selected semen (FSS) to produce primarily female calves that are early weaned at 3 mo of age. Dams are finished on a high concentrate diet and harvested before 30 mo of age. The objectives of this research were to: 1) build a dynamic model of an AHNC beef production system to quantify system biological and economic efficiency; 2) compare effects of utilizing FSS vs. conventional semen on biological and economic efficiency; 3) evaluate what-if scenarios to determine the effects on biological and economic efficiency of changing variables ±5%, 10%, 15%, and 20% from initial observed values; and 4) evaluate the effects on biological and economic efficiency of changing variables ±10% from initial observed values. A model was built over a 21-yr horizon using Stella Architect. Biological parameter values in the model were based on the 6 yr of data collected from the management of an AHNC demonstration herd. In the model animal, total digestible nutrients (TDN) intake, hot carcass weight (HCW), and age at harvest were randomized. Feed, animal, and carcass prices included in the model were based on 10 yr of historical U.S. price data. Key response variables were biological and economic efficiency (mean ± SD). Biological efficiency was defined as the ratio of output (kilograms of HCW produced) to input (lifetime kilograms of feed TDN consumed), and economic efficiency was measured using a benefit-cost ratio (BCR) and unit variable cost (UVC). Over 40 simulation runs, the predicted mean biological efficiency was 0.0714 ± 0.0008. Economic efficiency was 0.95 ± 0.02 and US $445.41 ± 0.06 for BCR and UVC, respectively. Biological and economic efficiency was improved in the conventional semen scenario; biological efficiency was 0.0738 ± 0.0008, and BCR and UVC were 0.99 ± 0.04 and US $407.24 ± 0.006, respectively. Under this parameterization and market conditions, the AHNC beef production system failed to achieve profitability under any scenario that was evaluated. However, this review did not account for the potential increased genetic benefit from a decreased generation interval and the reduction in feed energy in comparison to a conventional cow/calf system.

A retrospective analysis to estimate the healthcare resource utilization and cost associated with treatment-resistant depression in commercially insured US patients.

OBJECTIVE: The economic burden of commercially insured patients in the United States with treatment-resistant depression and patients with non-treatment-resistant major depressive disorder was compared using data from the Optum Clinformatics™ claims database. METHODS: Patients 18-63 years on antidepressant treatment between 1/1/13 and 9/30/13, who had no treatment claims for depression 6 months before the index date (first antidepressant dispensing), and who had a major depressive disorder or depression diagnosis within 30 days of the index date, were included. Treatment-resistant depression was defined as receiving 3 antidepressant regimens during 1 major depressive disorder episode. Patients with treatment-resistant depression were matched with patients with non-treatment-resistant major depressive disorder at a 1:4 ratio using propensity score matching. The study consisted of 1-year baseline (pre-index) and 2-year follow-up (post index) periods. Cost outcomes were compared using a generalized linear model. RESULTS: 2,370 treatment-resistant depression and 9,289 non-treatment-resistant major depressive disorder patients were included. In year 1 of the follow-up period, compared with non-treatment-resistant major depressive disorder, patients with treatment-resistant depression had: more emergency department visits (odds ratio = 1.39, 95% confidence interval = 1.24-1.56); more inpatient hospitalizations (odds ratio = 1.73, 95% confidence interval = 1.46-2.05); longer hospital stays (mean difference vs non-treatment-resistant major depressive disorder = 2.86, 95% confidence interval = 0.86-4.86 days); and more total healthcare costs (mean difference vs non-treatment-resistant major depressive disorder = US$3,846, 95% confidence interval = $2,855-$4,928). These patterns remained consistent in year 2 of the follow-up period. CONCLUSION: Treatment-resistant depression was associated with higher healthcare resource utilization and costs versus non-treatment-resistant major depressive disorder in this commercially insured cohort of patients in the United States.

Incremental Health Care Burden of Treatment-Resistant Depression Among Commercial, Medicaid, and Medicare Payers.

OBJECTIVE: This study compared health care use and costs among patients with treatment-resistant versus treatment-responsive depression across Medicaid, Medicare, and commercial payers. METHODS: A retrospective cohort study was conducted by using Truven Health Analytics' commercial (2006-2017; N=111,544), Medicaid (2007-2017; N=24,036), and Medicare supplemental (2006-2017; N=8,889) claims databases. Participants were adults with major depressive disorder who had received one or more antidepressant treatments. Treatment resistance was defined as failure of two or more antidepressant treatments of adequate dose and duration. Annual use (hospitalizations and outpatient and emergency department [ED] visits) and costs were compared across patients by treatment-resistant status in each payer population. Incremental burden of treatment-resistant depression was estimated with regression analyses. Monthly changes in costs during 1-year follow-up were assessed to understand differential cost trends by treatment-resistant status. RESULTS: In the three payer populations, patients with treatment-resistant depression incurred higher health care utilization than those with treatment-responsive depression (hospitalization, odds ratios [ORs]=1.32-1.76; ED visits, ORs=1.38-1.45; outpatient visits, incident rate ratio=1.29-1.54; p<0.001 for all). Compared with those with treatment-responsive depression, those with treatment resistance incurred higher annual costs (from $4,093 to $8,054 higher; p<0.001). Patients with treatment-resistant depression had higher costs at baseline compared with patients with treatment-responsive depression and incurred higher costs each month throughout follow-up. CONCLUSIONS: Treatment-resistant depression imposes a significant health care burden on insurers. Treatment-resistant depression may exist and affect health care burden before a patient is identified as having treatment-resistant depression. Findings underscore the need for effective and timely treatment of treatment-resistant depression.

Pitfalls of Cost-Effectiveness Analysis in Practice: A TRD Case Example in the United States with Esketamine Versus Oral Antidepressants.

DISCLOSURES: The writing of this letter was supported by Janssen Scientific Affairs. The authors are employees of Janssen Scientific Affairs or Janssen Global Services (Johnson & Johnson).

Use of home health and other healthcare delivery pathways among privately insured patients with and without treatment-resistant depression.

Objective: To assess the real-world use of home health services (HHS) among patients with major depressive disorder (MDD) with and without treatment-resistant depression (TRD).Methods: Adults (18-64 years) from a commercial claims database (07/2009 to 03/2015) were categorized into three cohorts: "TRD"(N = 6411), "non-TRD MDD"(N = 33,068), "non-MDD"(N = 149,884) stratified based on use of HHS (HHS vs. no-HHS). Healthcare resource utilization (HRU) and costs were evaluated up to two years following the first antidepressant pharmacy claim using descriptive statistics. HRU (e.g. inpatient, outpatient, emergency department visits) and costs were measured per-patient-per-year (PPPY) in 2015 USD.Results: During the follow-up period, 18.0% of TRD, 12.4% of non-TRD MDD, and 6.5% of non-MDD patients received HHS. Mean all-cause healthcare costs PPPY were numerically higher among patients with HHS use. Among the TRD cohort, patients using HHS had healthcare costs of $40,040 PPPY while patients with TRD and no-HHS had healthcare costs of $12,272 PPPY. Within the non-TRD MDD cohort, HHS users incurred healthcare costs of $28,767 PPPY and non-HHS users incurred costs of $7227 PPPY. Patients without MDD who used HHS had annual healthcare costs of $22,340 while non-MDD patients who did not use HHS had healthcare costs of $3479 PPPY. However, among HHS users, HHS costs represented a relatively small proportion of total healthcare costs.Conclusions: The high proportion of TRD patients using HHS suggests it is a utilized healthcare delivery pathway by TRD patients.

Descriptive analysis of the economic burden of treatment resistance in a major depressive episode.

Objectives: To assess characteristics and healthcare costs associated with pharmacologically treated episodes of treatment-resistant depression (TRD) in patients with major depressive disorder (MDD).Methods: Patients aged ≥18 years with continuous health plan enrollment for ≥12 months before and after a newly observed MDD diagnosis (observed between 1 January 2010 and 31 December 2015) were included in this retrospective claims-based analysis. A pharmacologically treated episode was defined as beginning at the date of the first MDD diagnosis and ending when a gap of 180 days occurred between MDD diagnoses, or when a gap of 180 days occurred following the end of the antidepressant (AD)/antipsychotic (AP) drug supply. When such a gap occurred, the episode end date was determined to be either the date of the last MDD diagnosis or date of the end of AD/AP drug supply, whichever was later. An episode was considered TRD if ≥3 AD regimens occurred. Episode duration, medication regimens used, and relapse hospitalization were reported for TRD and non-TRD MDD episodes. Total all-cause and per-patient-per-month (PPPM) healthcare costs (in 2016 $) were estimated.Results: Of 48,440 patients identified with ≥1 AD-treated MDD episode, the mean (SD) age was 39 (15) years, and 62% were female. Of all episodes, 7% were TRD, with a mean duration of 571 (285) days vs. 200 (198) days for non-TRD MDD episodes. Mean total all-cause costs were $19,626 ($44,160) for TRD and $7440 ($25,150) for non-TRD MDD episodes.Conclusions: Results show TRD episodes are longer and costlier than non-TRD MDD episodes, and that higher costs are driven by episode duration. Longer episodes imply protracted suffering for patients with TRD and increased burden on caregivers. Effective intervention to shorten TRD episodes may lessen disease burden and reduce costs.

US Integrated Delivery Networks Perspective on Economic Burden of Patients with Treatment-Resistant Depression: A Retrospective Matched-Cohort Study.

OBJECTIVE: Our objective was to assess healthcare resource utilization (HRU) and costs among patients with major depressive disorder (MDD) with and without treatment-resistant depression (TRD) and those without MDD in US Integrated Delivery Networks (IDNs). METHODS: This was a retrospective matched-cohort study. The Optum© Integrated Claims Electronic Health Record de-identified database was used to identify adult patients with TRD (January 2011-June 2017) across US IDNs. TRD patients were propensity score matched 1:1 with non-TRD MDD and non-MDD patients on demographics. Rates of HRU and costs were compared up to 2 years following the first antidepressant pharmacy claim (or randomly imputed date for non-MDD patients) using negative binomial and ordinary least squares regressions, respectively, with 95% confidence intervals (CIs) from nonparametric bootstraps (costs only) adjusted for baseline comorbidity index and costs. RESULTS: All 1582 TRD patients were matched to non-TRD MDD and non-MDD patients and evaluated. TRD patients were on average 46 years old, and 67% were female. Mean duration of observation was 20.1, 19.6, and 17.9 months in the TRD, non-TRD MDD, and non-MDD cohorts, respectively. Patients with TRD had significantly higher rates of HRU than did non-TRD MDD patients (inpatient visits 0.35 vs. 0.16 per patient per year [PPPY]; adjusted incidence rate ratio [IRR] 2.04 [95% CI 1.74-2.39]) and non-MDD patients (0.35 vs. 0.09 PPPY, adjusted IRR 3.05 [95% CI 2.54-3.66]). TRD patients incurred significantly higher costs PPPY than did non-TRD MDD patients ($US25,807 vs. 13,701, adjusted cost difference $US9479 [95% CI 7071-11,621]) and non-MDD patients ($US25,807 vs. 8500, adjusted cost difference $US11,433 [95% CI 8668-13,876]). CONCLUSIONS: HRU and costs associated with TRD are significant in US IDNs.

An Evaluation of the Clinical and Economic Burden Among Older Adult Medicare-Covered Beneficiaries With Treatment-Resistant Depression.

OBJECTIVE: To compare the clinical and economic burden of treatment-resistant depression (TRD) among older adult patients with major depressive disorder (MDD) to non-TRD MDD and non-MDD patients. METHODS: Retrospective cohort study using 5% Medicare data (January 1, 2012-December 31, 2015) for MDD patients aged ≥65 years who were defined as TRD if they received ≥2 antidepressant treatments in the current episode. MDD patients not meeting TRD criteria were deemed non-TRD MDD; those without an MDD diagnosis were categorized as non-MDD. All were required to have continuous health plan enrollment for ≥6 months pre- and ≥12 months postindex date (index: first antidepressant claim/random [non-MDD]). Three cohorts were matched, and generalized linear and Cox proportional hazards models were used to compare medication use, healthcare resource utilization, costs, and risks of initial hospitalization and readmission ≤30 days postdischarge from initial hospitalization. RESULTS: After matching, 178 patients from each cohort were analyzed. During 12 months of follow-up, TRD patients had higher use of different antidepressants and antipsychotics, higher inpatient and emergency room visits, longer inpatient stays, and higher total healthcare costs ($24,543 versus $16,059, $8,058) than non-TRD MDD and non-MDD cohorts, respectively (all p <0.05). Risk of initial hospitalization was higher in the TRD (hazard ratio [HR] = 3.60, 95% confidence interval [CI] = 2.08-6.23) and non-TRD MDD cohorts (HR = 1.82, 95% CI = 1.02-3.25) than the non-MDD cohort. CONCLUSIONS: The burden of MDD among older adult Medicare beneficiaries is substantial, and even greater among those with TRD compared to non-TRD MDD, demonstrating the need for more effective treatments than those currently available.