Barriers to Esketamine Nasal Spray Treatment Among Adults With Treatment-Resistant Depression.

Background: Under a risk evaluation and mitigation strategy program, esketamine nasal spray CIII requires self administration at a certified treatment center. Our objective was to identify factors associated with esketamine initiation and continuation.Methods: A retrospective observational cohort study was conducted among US adults who met treatment-resistant depression (TRD) criteria. Cases (n = 966) initiated esketamine between October 11, 2019, and February 28, 2022, and were compared to controls (n = 39,219) with TRD but no esketamine use. Outcomes included initiation, induction (8 administrations within 45 days), and interruptions (30-day treatment gap). Comorbid psychiatric conditions were identified using International Classification of Diseases, Tenth Revision, Clinical Modification, codes.Results: Cases resided significantly closer to treatment centers (8.9 vs 20.3 miles). Compared to 0-9 miles, initiation rate decreased by 11.9%, 50.8%, 68.1%, 75.9%, and 92.8% for individuals residing 10-19, 20-29, 30-39, 40-49, and 50+ miles from a center. After adjustment, factors associated with increased likelihood of initiation were posttraumatic stress disorder, major depressive disorder with suicidal ideation, and male sex, while increasing distance, substance use disorder, Medicaid, Charlson Comorbidity Index (CCI), and older age were associated with lower likelihood. Factors associated with lower likelihood of completing induction were Medicaid, low socioeconomic status (SES), CCI, and Hispanic communities. Factors associated with increased likelihood of interruption were alcohol use disorder, distance, and minority communities, while generalized anxiety disorder and Medicaid were associated with lower likelihood.Conclusions: Travel distance, insurance, low SES, and minority communities are potential barriers to treatment. Alternative care models may be needed to ensure adequate access to care.J Clin Psychiatry 2024;85(2):23m15102.

Treatment Patterns, Acute Healthcare Resource Use, and Costs of Patients with Treatment-Resistant Depression Completing Induction Phase of Esketamine in the United States.

BACKGROUND: This study aimed to understand treatment patterns, acute healthcare use, and cost patterns among adults with treatment-resistant depression (TRD) who completed induction treatment with esketamine nasal spray in the United States (US). Per label, induction is defined as administration twice a week for 4 weeks, after which maintenance is started on a weekly basis for 4 weeks, and thereafter, patients are treated weekly or bimonthly. METHODS: Adults with one or more esketamine claim (index date) on or after March 5, 2019 were selected from Optum's de-identified Clinformatics® Data Mart Database (January 2016-June 2022). Before the index date, patients had evidence of TRD and ≥ 12 months of continuous insurance eligibility (baseline period). Patients with eight or more esketamine treatment sessions were included in the main cohort. A subgroup included patients with one or more baseline mental health (MH)-related inpatient (IP) admission or emergency department (ED) visit (i.e., prior acute healthcare users). Treatment patterns were described during the follow-up period (index date until earliest of end of insurance eligibility or data); acute healthcare (i.e., IP and ED) resource use and costs (2021 US dollars) were reported during the baseline and follow-up periods. RESULTS: Of the 322 patients in the main cohort, 111 comprised the subgroup of prior acute healthcare users. During the follow-up period, mean time from index date to eighth esketamine session was 73.2 days in the main cohort and 78.8 days in the subgroup (per label, 28 days). Further, 75.2% of the main cohort and 73.9% of the subgroup completed four or more esketamine maintenance sessions following induction. In the main cohort, mean all-cause acute healthcare costs per patient per month (PPPM) decreased from baseline ($837) to follow-up ($770). Similar reductions were observed for mean MH-related acute healthcare costs PPPM (baseline $648, follow-up $577). In the subgroup, mean all-cause acute healthcare costs PPPM also decreased (baseline $2323, follow-up $1423), driven by mean MH-related acute healthcare costs PPPM (baseline $1880, follow-up $1139). Mean all-cause acute healthcare use per ten patients per month remained largely stable from baseline to follow-up in the main cohort (IP days: baseline 2.24, follow-up 2.13; ED visits: baseline 1.33, follow-up 1.45) and decreased in the subgroup (IP days: baseline 6.38, follow-up 4.56; ED visits: baseline 2.58, follow-up 2.41). Trends in mean MH-related acute healthcare use were similar. CONCLUSION: Patients generally required more time than label recommendation to complete esketamine induction treatment, and most went on to have 12 or more esketamine sessions. Completion of induction treatment correlated with reductions in mean all-cause and MH-related acute healthcare costs. Larger reductions were seen in the subgroup of prior acute healthcare users.

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.

The clinical, economic, and patient-centric burden of insomnia symptom severity in adults with major depressive disorder in the United States.

INTRODUCTION: Insomnia is prevalent in adults with major depressive disorder (MDD) and is a key diagnostic criterion of MDD; however, little is understood about the burden of insomnia symptom severity in MDD. We evaluated the relationship between insomnia symptom severity and the clinical, economic, and patient-centric burden among community-dwelling individuals with MDD. METHODS: Respondents with diagnosed depression who reported insomnia symptoms in the past 12 months (N = 4402) were identified from the 2019 United States National Health and Wellness Survey. Multivariable analyses assessed the association of Insomnia Severity Index (ISI) with health-related outcomes while controlling for sociodemographic and health characteristics. Further analyses also controlled for depression severity (9-item Patient Health Questionnaire). RESULTS: Mean ISI score was 14.3 ± 5.6. Higher ISI was associated with greater depression severity (r = .51, p < .001). After adjustments, a one-standard deviation (5.6-point) increase in ISI score was significantly associated with higher depression (rate ratio [RR] = 1.36), anxiety (RR = 1.33) and daytime sleepiness (RR = 1.16) levels, more healthcare provider (RR = 1.13) and emergency room visits (RR = 1.31), hospitalizations (RR = 1.21), work productivity and activity impairment (RRs = 1.27 and 1.23, respectively), and poorer mental and physical health-related quality of life (ß = -3.853 and -1.999, respectively) (p < .001). These findings remained statistically significant when controlling for concurrent depression severity. CONCLUSION: In adults with MDD, greater insomnia symptom severity is associated with worse health-related outcomes, which suggests the importance of addressing insomnia symptoms as a clinical target for treating MDD.

Access and real-world use patterns of esketamine nasal spray among patients with treatment-resistant depression covered by private or public insurance.

OBJECTIVE: To describe access and real-world use patterns of esketamine nasal spray among adults with treatment-resistant depression (TRD) with private or public insurance. METHODS: Adults with ≥1 claim for esketamine nasal spray were selected from Clarivate's Real World Data product (January 2016-March 2021). Patients with evidence of TRD initiating esketamine (index date) after 05 March 2019 were included. Esketamine access, as measured by pharmacy claim approval rate for each treatment session, and use patterns were described post-index (follow-up period). RESULTS: Among 535 patients with pharmacy claims for esketamine nasal spray (mean age 49.1 years; 65.4% females), 534 had the first esketamine claim being a pharmacy claim, of which 34.6% were approved, 46.3% were rejected, and 19.1% were abandoned. Main reasons for rejection included "claim not covered by plan" (57.1%), "claim errors" (52.6%), and "prior authorization required" (22.7%). The approval rate increased to 85.2% by the second esketamine treatment session. A total of 273 patients initiated esketamine (mean age 49.3 years; 66.3% females). Patients had a mean ± standard deviation (SD) of 11.8 ± 13.3 esketamine sessions over a mean ± SD of 11.8 ± 6.4 months; 47.6% of patients completed ≥8 sessions (i.e. the number of sessions in induction phase) over a mean ± SD of 80.1 ± 71.9 days (per label, 28 days); 48 (17.6%) patients completed induction per label, and among them 93.8% continued treatment. CONCLUSIONS: Initial access to esketamine nasal spray may be hindered by prior authorization or claim filing errors. Among patients who initiated esketamine, treatment compliance generally deviates from label recommendations; yet, most of those who received induction per label successfully transition to maintenance with esketamine.

Esketamine nasal spray is a novel therapy for treatment-resistant depression (TRD). In the United States, insurance plans often regulate access to esketamine. Additionally, for patients, it may be challenging to comply to the treatment schedule, because patients must receive esketamine in a certified treatment center, be monitored for 2 h for potential side effects, and they cannot drive until the next day. This real-world study used insurance claims data and found that patients with TRD had difficulties accessing esketamine. Among those with access, esketamine use patterns were suboptimal.

Esketamine nasal spray for major depressive disorder with acute suicidal ideation or behavior: description of treatment access, utilization, and claims-based outcomes in the United States.

AIMS: To describe real-world esketamine nasal spray access and use as well as healthcare resource use (HRU) and costs among adults with evidence of major depressive disorder (MDD) with suicidal ideation or behavior (MDSI). METHODS: Adults with ≥1 claim for esketamine nasal spray and evidence of MDSI 12 months before/on the date of esketamine initiation (index date) were selected from Clarivate's Real World Data product (01/2016-03/2021). Patients initiated esketamine on/after 03/05/2019 (esketamine approval for treatment-resistant depression; later approved for MDSI on 08/05/2020) were included in the overall cohort. Esketamine access (measured as approved/abandoned/rejected claims) and use were described post-index; HRU and healthcare costs (2021 USD) were described over 6 months pre- and post-index. RESULTS: Among 269 patients in the overall cohort with esketamine pharmacy claims, 46.8% had the first pharmacy claim approved, 38.7% had it rejected, and 14.5% abandoned their claim; 169 patients were initiated on esketamine in the overall cohort (mean age 40.9 years, 62.1% female); 45.0% had ≥8 esketamine treatment sessions (recommended per label) with a mean [median] of 85.0 [58.5] days from index to 8th session (per label 28 days). Among 115 patients with ≥6 months of data post-index, in the 6-month pre- and post-index, respectively, 37.4 and 19.1% had all-cause inpatient admissions, 42.6 and 33.9% had emergency department visits, 92.2 and 81.7% had outpatient visits; mean ± standard deviation all-cause monthly total healthcare costs were $8,371±$15,792 and $6,486±$7,614, respectively. LIMITATIONS: This was a descriptive claims-based analysis; no formal statistical comparisons were performed due to limited sample size as data covered up to 24 months of esketamine use in the US clinical setting. CONCLUSIONS: Nearly half of patients experience access issues with first esketamine nasal spray treatment session. All-cause HRU and healthcare costs trend lower in the 6 months after relative to 6 months before esketamine initiation.

Major depressive disorder (MDD), or clinical depression, can sometimes be accompanied by preoccupation with suicide along with suicidal behavior. Patients diagnosed with MDD with suicidal ideation or behavior (MDSI) can vary in their reactions to this condition, and some never seek treatment. This study investigated treatment patterns in real-world clinics of a recently approved nasal spray therapy, esketamine, which helps improve depressive symptoms in patients with MDSI. The study results highlight challenges related to esketamine treatment access, particularly for the first treatment session. Still, healthcare resource utilization and healthcare costs trended lower following treatment initiation with esketamine in MDSI, suggesting the potential benefits of esketamine in mitigating the clinical and economic burden of MDSI among those who gain access to the drug. Streamlining the approval process by health plan providers to remove hindrances related to compliance with plan requirements may ensure more timely access to esketamine for MDSI.

Treatment patterns, healthcare utilization, and costs of patients with treatment-resistant depression initiated on esketamine intranasal spray and covered by US commercial health plans.

AIMS: To describe real-world use of esketamine (ESK) intranasal spray and healthcare outcomes among patients with treatment-resistant depression (TRD) in the United States (US). METHODS: Adults with TRD initiated on ESK (index date) between 5 March 2019 (US approval date for TRD) and 31 October 2020 were sampled from IBM MarketScan Research Databases. TRD was defined as claims for ≥2 unique antidepressants during the same major depressive episode. Subgroups of the TRD cohort with comorbid cardiometabolic conditions, pain, anxiety disorder, and substance use disorder (SUD) were identified. Patients had ≥6 months of continuous health plan eligibility pre- and post-index. RESULTS: The TRD cohort comprised 269 patients; comorbidity subgroups included 123 (cardiometabolic), 144 (pain), 189 (anxiety disorder), and 58 (SUD) patients. Proportion of patients completing ≥8 ESK sessions (number of sessions in induction phase) was 61.3% in the TRD cohort and ranged from 60.2% (cardiometabolic subgroup) to 72.4% (SUD subgroup) in subgroups. Median frequency of induction sessions was every 5-8 days among the TRD cohort and subgroups. Mean mental health-related inpatient costs reduced from pre- to post-index periods in the TRD cohort (mean ± standard deviation [median] costs per-patient-per-6-months: $3,480 ± $13,328 [$0] pre-ESK initiation; $3,262 ± $16,666 [$0] post-ESK initiation; mean difference: -$218) and subgroups (largest decrease in cardiometabolic subgroup: $4,864 ± $14,271 [$0]; $2,792 ± $15,757 [$0]; -$2,072). Mean mental health-related emergency department (ED) costs decreased in the TRD cohort ($608 ± $2,525 [$0]; $269 ± $1,143 [$0]; -$339) and subgroups (largest decrease in the SUD subgroup: $1,403 ± $3,752 [$0]; $351 ± $868 [$0]; -$1,052). LIMITATIONS: This is a descriptive analysis; sample size for some comorbidity subgroups is small. CONCLUSIONS: The majority of patients completed ESK induction phase, and most dosing intervals were longer than the label recommendation. In this descriptive analysis, mental health-related inpatient and ED costs trended lower post-ESK initiation.

Social determinants and distance from certified treatment centers are associated with initiation of esketamine nasal spray among patients with challenging-to-treat major depressive disorder.

Indicated for treatment-resistant depression or major depression with suicidal ideation, esketamine (ESK) is self-administered under supervision at certified treatment centers. Our study was to determine if social determinants of health and distance were associated with ESK utilization. We conducted a retrospective cohort study among 308 US adults initiating ESK between October 11, 2019 and December 31, 2020 and 1540 propensity-score matched controls with treatment-resistant depression or major depression with suicidal ideation. Adjusting for demographics, prior health care utilization and comorbidities, social determinant variables and distance were regressed separately on each outcome: ESK initiation, failure to complete induction (8 treatments in 45 days), and discontinuation within 6 months. ESK initiation was associated with higher population density (odds ratio [OR]: 2.12), American Indian, Alaska Native, Native Hawaiian, Other Pacific Islander (OR: 3.19), and mental health (OR: 1.55) and primary care providers (OR: 1.55) per capita. Lower likelihood of ESK initiation was associated with living > 7.2 miles from a treatment center (OR: 0.75), living in rural areas (OR: 0.64), and percent non-Hispanic African American (OR: 0.58) and Hispanic (OR: 0.40). Health care providers should tailor patient engagement strategies to mitigate potential barriers to initiating and continuing appropriate treatment. Failing to complete induction was associated with substance use disorder and longer distance to treatment center was associated with discontinuation (hazard ratio: 1.48), as was percent Asian population (hazard ratio: 1.37). Prior psychiatric care and residence in counties with high rates of primary care providers per capita, unemployment, and high school graduation were associated with both higher likelihood of completing induction and lower likelihood of discontinuation.

The real-world burden of adults with major depressive disorder with moderate or severe insomnia symptoms in the United States.

BACKGROUND: Although insomnia is a common core symptom of major depressive disorder (MDD), the burden of moderate-to-severe insomnia symptoms in patients with MDD is not well-understood. This study quantified the clinical, patient-centric, and economic burden of adults with MDD with moderate-to-severe insomnia symptoms (MDDIS) compared to adults with MDD with no-to-mild insomnia symptoms (other-MDD) and adults without MDD. METHODS: Data from 2019 US National Health and Wellness Survey identified adults self-reporting physician-diagnosed depression, stratified by insomnia status (MDDIS: Insomnia Severity Index [ISI] score ≥15; other-MDD: ISI score <15), and adults not reporting depression (non-MDD). Other-MDD and non-MDD were matched 2:1 to MDDIS on age/sex/race. Matched bivariate analyses examined differences in health-related outcomes by depression-insomnia status. RESULTS: Of 74,994 survey respondents, 2045 (2.7%) were classified as MDDIS, 8220 (11.0%) as other-MDD, and 59,859 (79.8%) as non-MDD. MDDIS respondents (vs other-MDD and non-MDD) reported greater depression severity, anxiety severity, daytime sleepiness, activity impairment, direct costs, and costs due to work productivity impairments, and lower mental and physical functioning (all P < 0.05). LIMITATIONS: Depression diagnosis was not based on clinical/diagnostic interview; causal relationships cannot be determined due to the cross-sectional design. CONCLUSIONS: Among US adults with MDD, presence of moderate-to-severe insomnia symptoms is associated with additional burden and notable impairments across several health outcomes versus those with MDD but no-to-minimal insomnia symptoms and general population without MDD. This study highlights the burden of MDDIS and the need for better identification and management of moderate-to-severe insomnia symptoms in adults with MDD.

Characteristics of Real-world Commercially Insured Patients With Treatment-resistant Depression Initiated on Esketamine Nasal Spray or Conventional Therapies in the United States.

PURPOSE: This study aimed to characterize patients with treatment-resistant depression (TRD) initiating esketamine or conventional therapies. METHODS: Adults with major depressive disorder (MDD) were selected from the IBM MarketScan Databases. A claims-based algorithm identified patients with evidence of TRD, defined as initiation of a new antidepressant therapy after 2 different antidepressant trials of adequate dose and duration during the most recent major depressive episode. Patients receiving treatment on/after March 5, 2019 (esketamine approval date for TRD), were classified to the esketamine cohort if they newly initiated esketamine (index date) or to the TRD conventional therapies cohorts if they newly initiated electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or pharmacologic therapies (index date was the therapy initiation date, prioritizing ECT, then TMS, then pharmacologic antidepressant therapies). Patient characteristics in the 6 months before therapy initiation were described. FINDINGS: The esketamine cohort included 246 patients (mean age, 46.5 years; 63.0% female), and the TRD conventional therapies cohorts included 104,164 patients (mean age, 46.9 years; 74.8% female; 0.4% initiated ECT, 1.2% initiated TMS). During the 6 months preindex, in the esketamine and TRD conventional therapies cohorts, 77.6% and 41.4% received psychotherapy and 82.9% and 34.2% had a psychiatrist visit, respectively. Most patients had outpatient care for MDD in the esketamine (91.9%) and TRD conventional therapies (63.6%) cohorts; 57.3% and 21.0% received care at specialized mental health care settings. MDD was classified as "severe" among 81.3% and 35.1% of patients in the esketamine and TRD conventional therapies cohorts . Preindex mental health-related (MHR) inpatient admissions and emergency department visits were identified in 12.2% and 16.3% of the esketamine cohort and in 8.2% and 10.3% of the TRD conventional therapies cohort. Before therapy initiation, 34.6% and 17.6% of the esketamine and TRD conventional therapies cohorts received ≥3 unique antidepressants. Suicidal ideation or behavior was observed in 8.5% and 3.6% of the esketamine and TRD conventional therapies cohorts pretherapy initiation. Mean monthly all-cause health care costs in the esketamine cohort were $2532 (58.2% MHR); in the TRD conventional therapies cohorts, costs were $1873 (32.4% MHR). IMPLICATIONS: Among patients with TRD, those initiating esketamine relative to conventional therapies displayed higher MDD severity, used more MHR inpatient/emergency department services and antidepressant treatments, and incurred higher health care costs 6 months pretherapy initiation. These findings suggest potential benefits of identifying and treating patients with TRD earlier with more effective treatments and should inform payers in consideration of esketamine coverage.

Clinical and economic burden of major depressive disorder with acute suicidal ideation or behavior in a US Veterans Health Affairs database.

OBJECTIVE: Although a high incidence of major depressive disorder (MDD) and an increased risk of suicide are observed among the veteran population, there are yet limited real-world data characterizing patients with MDD with acute suicidal ideation/behavior (MDSI) in the Veterans Health Administration (VHA) system. We assessed the clinical and economic burden, including comorbidities, treatment patterns, health care resource utilization, and health care costs, among veterans and their family members with MDSI within the VHA system. METHODS: This retrospective, longitudinal analysis of VHA datasets (10/1/2015-3/31/2018) evaluated the clinical and economic burden associated with MDSI and compared this population with matched MDD alone (i.e. MDD diagnosis without acute suicidal ideation/behavior) and non-MDD (i.e. neither MDD nor acute suicidal ideation/behavior) cohorts. RESULTS: Among 11,203 patients with MDSI, the proportions of patients who filled a prescription for ≥1 antidepressant during the 12-month pre- and 6-month post-periods were significantly higher compared with patients with MDD alone (53.7% vs 28.8%, p < .05; and 72.3% vs 44.1%, p < .05; respectively). During the 12-month pre-period, the MDSI cohort had the highest proportion of patients with ≥1 mental health-related inpatient visit compared with the MDD alone and non-MDD cohorts (13.2% vs 2.3% vs 1.4%, respectively; p < .05), and the highest mental health-related costs per patient ($8853 vs $1913 vs $1079, respectively). For the 6-month post-period, the MDSI cohort had the highest proportion of patients with ≥1 mental health-related inpatient visit compared with the MDD alone and non-MDD cohorts (60.4% vs 7.9% vs 0.8%, respectively; p < .05), and had the highest mental health-related costs per patient ($20,334 vs $4803 vs $545, respectively). CONCLUSIONS: Findings demonstrate significant clinical and economic burden for those in the VHA system diagnosed with MDSI and highlight unmet needs and opportunities for improving the care of this vulnerable group.

There are limited real-world data regarding patients diagnosed with major depressive disorder and having suicidal thoughts/behavior (MDSI) in the Veterans Health Administration (VHA) system. We examined data on 11,203 patients with MDSI from the VHA between October 1, 2015 and March 31, 2018. We compared patients with MDSI with patients with major depressive disorder alone (MDD) and patients with no depression (non-MDD). Our results showed that patients with MDSI were treated with more antidepressant therapy, had more hospital stays (inpatient visits), and incurred greater costs than the MDD and non-MDD patients. These results highlight the unmet need and potential opportunity to improve patient care among veterans and their families with MDSI.

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.

Systematic literature review of schizophrenia clinical practice guidelines on acute and maintenance management with antipsychotics.

Clinical practice guidelines (CPGs) translate evidence into recommendations to improve patient care and outcomes. To provide an overview of schizophrenia CPGs, we conducted a systematic literature review of English-language CPGs and synthesized current recommendations for the acute and maintenance management with antipsychotics. Searches for schizophrenia CPGs were conducted in MEDLINE/Embase from 1/1/2004-12/19/2019 and in guideline websites until 06/01/2020. Of 19 CPGs, 17 (89.5%) commented on first-episode schizophrenia (FES), with all recommending antipsychotic monotherapy, but without agreement on preferred antipsychotic. Of 18 CPGs commenting on maintenance therapy, 10 (55.6%) made no recommendations on the appropriate maximum duration of maintenance therapy, noting instead individualization of care. Eighteen (94.7%) CPGs commented on long-acting injectable antipsychotics (LAIs), mainly in cases of nonadherence (77.8%), maintenance care (72.2%), or patient preference (66.7%), with 5 (27.8%) CPGs recommending LAIs for FES. For treatment-resistant schizophrenia, 15/15 CPGs recommended clozapine. Only 7/19 (38.8%) CPGs included a treatment algorithm.

Patient Journey of Veterans with Schizophrenia: An Analysis of Treatment Patterns, Healthcare Resource Utilization and Costs.

INTRODUCTION: Little is known about the burden of schizophrenia among United States veterans early after diagnosis. This retrospective study describes treatment patterns, healthcare resource utilization (HRU) and healthcare costs among veterans with a recent schizophrenia diagnosis. METHODS: Adults with a schizophrenia diagnosis recorded between 1 April 2014 and 31 December 2017 and no history of schizophrenia over the preceding 12 months were identified from a Veterans Health Administration (VHA) database. Continuous enrollment in the VHA was required for ≥ 12 months before and after the index date when the first schizophrenia diagnosis code was identified. Baseline characteristics and follow-up treatment patterns, HRU and costs were examined descriptively. RESULTS: The study population (20,389 patients) had a high baseline mental health comorbidity burden. Despite a schizophrenia diagnosis, 32.1% of patients received no antipsychotic medication during the follow-up period. Among those with ≥ 1 antipsychotic prescription fill, 64.0% received ≥ 1 oral antipsychotic (OAP) therapy and 11.6% received ≥ 1 long-acting injectable (LAI). A delay was observed between diagnosis and treatment for both OAPs (39.0 ± 67.2 days) and LAIs (69.4 ± 96.2 days). Adherence to therapy (defined as proportion of days covered ≥ 80%) was greater with LAIs (34.5%) vs OAPs (27.3%). Inpatient stays were reported for 33.8% of patients during the 12-month follow-up period, and 5.5% of patients had readmissions. All-cause inpatient stay costs with 12-month follow-up equaled $7999 per patient per year. CONCLUSIONS: These data indicate that pharmacotherapy after a recent diagnosis of schizophrenia in the VHA system is suboptimal, and that these patients face a considerable burden in terms of hospitalization, other HRU, and healthcare costs.

Patient profiles, initial hospital encounter characteristics, and hospital re-encounters of patients with a hospital emergency department visit or inpatient admission for major depressive disorder.

OBJECTIVES: To gain a better understanding of the characteristics of patients with a hospital encounter for major depressive disorder (MDD) and evaluate associated hospital resource utilization, hospital charges and costs, and hospital re-encounters. METHODS: Adult patients with a hospital encounter (i.e. emergency department [ED] visit only or inpatient admission) with MDD as the primary discharge diagnosis (index event) during July 2018‒March 2019 were selected from the Premier Healthcare Database. Patient characteristics, hospital resource utilization, and hospital charges and costs were evaluated during index events. During a 12-month follow-up, hospital re-encounters (MDD-related and all-cause ED visit only or inpatient readmissions) were examined. RESULTS: The study population included 77,178 patients with an index hospital encounter (ED visit only: 49.9%; inpatient admission: 50.1%) for MDD. The most common secondary mental health-related diagnosis was suicidal ideation/behavior, which was recorded in 51.8% of patients. The mean age was 38.2 years, 53.0% were female, and 72.1% were Caucasian. Among patients with an ED visit only, the mean index hospital charges and costs were $3,608 and $639, respectively. Among those with inpatient admissions, the mean length of stay was 4.9 days, and the mean index hospital charges and costs were $17,107 and $6,095, respectively. During the 12-month follow-up, 13.3% of patients in the overall study population had an MDD-related hospital re-encounter (primary or secondary discharge diagnosis code indicating MDD); nearly one-third (31.3%) occurred within 30 days post-discharge. During the follow-up, 28.1% had an all-cause hospital re-encounter with 29.7% having occurred within 30 days post-discharge. LIMITATIONS: Due to constraints of the Premier Healthcare Database, healthcare resource utilization and costs outside of the hospital could not be evaluated. CONCLUSIONS: Patients with a hospital encounter for MDD are relatively young, commonly have suicidal ideation/behavior, utilize substantial hospital resources, and have a high risk for a hospital re-encounter in the 30 days post-discharge.

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.

Associations Between Relapses and Psychosocial Outcomes in Patients With Schizophrenia in Real-World Settings in the United States.

Aim: To assess associations between relapses and psychosocial outcomes in adult patients with schizophrenia treated in United States (US) healthcare settings. Methods: Data were derived from a point-in-time survey of psychiatrists and their patients with schizophrenia conducted across the US, France, Spain, China, and Japan between July and October 2019. For the purposes of this analysis, only data from US practitioners and patients were included. Disease-specific programmes (DSPs) are large surveys with a validated methodology conducted in clinical practise; they describe current disease management, disease burden, and associated treatment effects (clinical and physician-perceived). Participating psychiatrists completed patient record forms for their next 10 consecutive adult consulting patients with schizophrenia, with the same patients invited to voluntarily complete a patient self-completion (PSC) questionnaire. Surveys contained questions on the patients' disease background, treatment history, prior hospitalisation due to schizophrenia relapse and a series of psychosocial outcomes. Associations between relapses in the last 12 months and psychosocial outcomes were examined using multiple regression. Results: A total of 124 psychiatrists provided data on 1,204 patients. Of these, 469 patients (mean age, 39.6 years; 56.5% male) had known hospitalisation history for the last 12 months and completed a PSC; 116 (24.7%) patients had ≥1 relapse. Compared to patients without relapses, patients who relapsed were more likely to be homeless, unemployed, previously incarcerated, and currently have difficulties living independently (all p < 0.05). Patients who experience a relapse also had greater working impairment and poorer quality of life compared with those who did not relapse. In general, psychosocial outcomes became poorer with an increasing number of relapses. Conclusions: In this population of patients with schizophrenia from the US, relapse was significantly associated with poor psychosocial outcomes, with a greater number of relapses predicting worse outcomes. Early intervention to reduce the risk of relapse may improve psychosocial outcomes in patients with schizophrenia.