SUMMARY

• Retrospective analyses to evaluate baseline characteristics of patients treated with SPRAVATO and patients with treatment-resistant depression (TRD) who had not been treated with SPRAVATO found that SPRAVATO was being administered to patients who were generally sicker, had more refractory depression, and had a higher burden of disease than typical patients with TRD.^1,2
• A retrospective, observational cohort study in commercially insured adults evaluated baseline characteristics, healthcare resource utilization, and healthcare costs of patients initiated on SPRAVATO in a real-world setting (all comers) vs patients with TRD treated with electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS), or patients with TRD receiving benchmark pharmacological therapies. Patients receiving SPRAVATO appeared generally more severe (in terms of baseline healthcare resource utilization and healthcare costs) than patients with TRD receiving benchmark pharmacological therapies, slightly more severe than patients with TRD receiving TMS, and distinctly less severe than patients with TRD receiving ECT.²
• The results of another retrospective study evaluating access and real-world use patterns of SPRAVATO in adult patients with TRD with private or public insurance supported the opinion from an expert clinical consensus panel recommending the need for individualized treatment duration for patients with TRD.³
• A retrospective study of closed claims from the Komodo Research Database and depression scores from the Komodo Clinical Observations database found that most patients completed induction but that the median time to complete induction (64 days) was much longer than the 28 days specified in the prescribing information; however, the dose frequency during the early part of maintenance was generally aligned to the weekly frequency recommended in the prescribing information. The median time to discontinuation of SPRAVATO was 8.2 months.⁴
• A retrospective study was conducted to describe characteristics, healthcare resource utilization (HRU), and healthcare costs among patients with major depressive disorder and acute suicidal ideation or behavior (MDSI) before and after SPRAVATO or other therapy initiation (i.e., ECT, antidepressant with antipsychotic augmentation, antidepressant monotherapy).⁵ Mean all-cause medical costs were highest in the ECT cohort ($4624), followed by the AP augmentation cohort ($2163), the SPRAVATO cohort ($1869), and the AD monotherapy cohort ($863).
• See Table: SPRAVATO Real-World Use Study Summaries below for details.

SPRAVATO Real-World Use Study Summaries

Study Design	Results
Treatment-Resistant Depression
Cepeda M, Kern DM, Canuso CM. At baseline patients treated with esketamine have higher burden of disease than other patients with treatment resistant depression: learnings from a population based study. Depress Anxiety. 2021;38(5):521-527. doi: 10.1002/da.23138
Retrospective analysis to evaluate baseline characteristics of patients currently treated with SPRAVATO and patients with TRD who have not been treated with SPRAVATO (TRD control group)1 TRD was defined as present for patients with a diagnosis of MDD who were dispensed 3 distinct ADs or 1 AD and 1 antipsychotic in 1 year. Data Source: IBM MarketScan® CCAE Database (to March 2020) and MDCD (to December 2019) Inclusion Criteria: SPRAVATO group: all patients treated with SPRAVATO in the database (not required to have TRD) TRD Control Group: patients with TRD defined as patients with diagnosis of MDD who were dispensed 3 distinct ADs or 1 AD and 1 antipsychotic in 1 year Index Date: date of exposure to SPRAVATO or when identified to have TRD (received third AD or the antipsychotic) Post Hoc Analysis: A TMS group, comprised of patients who had undergone a TMS procedure recorded for the first time in the database, were included as a comparator to the SPRAVATO group. Statistics: To compare baseline characteristics between the SPRAVATO and TRD control group, SMDs were calculated. SMD is the difference in prevalence of a specific characteristic in the 2 cohorts divided by the SD of the difference. A large absolute value SMD on a covariate is an indication of a significant disparity between the 2 groups. An SMD more than 0.1 has been used as an ad hoc method for indicating a “large” difference.	CCAE Analysis (SPRAVATO: n=418; TRD control: n=830,047) Patients in the SPRAVATO group had higher severity of illness and higher burden of disease. 79.19% vs 29.28% (SMD: 0.48), respectively, had a history of severe major depression, 27.03% vs 6.93% (SMD: 0.34) had a history of suicidal thoughts, and 23.21% vs <1% (SMD: 0.48) had undergone TMS. Patients in the SPRAVATO group had higher exposure to antipsychotics (SMD: 0.40), antiepileptics (SMD: 0.36), and hypnotics and sedatives (SMD: 0.21) than the TRD control group. The percentage of patients with ≥4 ADs in the year before the index date was higher in the SPRAVATO group vs the TRD control group (12.92% vs 7.5%, respectively [SMD: 0.12]). Patients in the SPRAVATO group had significantly more outpatient visits to HCPs than the control group (mean number of visits, 50.83 vs 27.14, respectively [SMD: 0.49]). MDCD Analysis (SPRAVATO: n=50; TRD control: n=312,459) Medicaid patients with TRD had a higher burden of disease than commercially insured patients with TRD. Patients in the SPRAVATO group had a higher severity of illness and burden of disease vs TRD control group, consistent with CCAE analysis. TMS Post Hoc Analysis (n=7529) Patients in the TMS group had more severe depression than patients in the SPRAVATO group (93.80% vs. 79.19%). Psychiatric comorbidities were more common in SPRAVATO group than the TMS group as well as previous exposure to ECT (11.24% vs. 5.30%). Outpatient visits were higher in the SPRAVATO group than in the TMS group (53 visits in the previous year vs. 43).
Karkare S, Zhdanava M, Pilon D, et al. Characteristics of real-world commercially insured patients with treatment-resistant depression initiated on esketamine nasal spray or conventional therapies in the United States. Clin Ther. 2022;44(11):1432-1448. doi: 10.1016/j.clinthera.2022.09.005
Retrospective, descriptive cohort study evaluating baseline demographic and clinical characteristics, specialized mental health service use, HRU, and health care costs of patients before being treated with SPRAVATO (all comers) as well as patients with TRD treated with conventional therapies, including ECT, TMS, or pharmacologic therapies2 Data Source: IBM® MarketScan® Commercial and Medicare Supplemental Databases (01/01/2010-07/31/2020) Index Date: date SPRAVATO or conventional therapy initiated Inclusion Criteria: ≥1 claim with a diagnosis for MDD during the study period; ≥6 months of continuous insurance eligibility before the index date; ≥18 years of age at the index date; therapy started during the most recent MDE at the time of or after evidence of TRD was observed and on or after 03/05/2019 SPRAVATO cohort: ≥1 claim for SPRAVATO TRD conventional therapies cohort: evidence of TRD during the most recent major depressive episode; ≥1 claim for either ECT or TMS, or ≥1 claim for a newly initiated AD-monotherapy with either escitalopram, desvenlafaxine, vortioxetine, or bupropion or with adjunctive aripiprazole, bupropion, gabapentin Exclusion Criteria: TRD conventional therapies cohort: ≥1 claim for SPRAVATO; Evidence of the index regimen in the 6-month pre-index period	Patient Characteristics SPRAVATO cohort (N=246): mean age, 46.5 years; female, 63%; evidence of severe MDD, 81.3; suicidal ideation or behavior, 8.5%. TRD conventional therapies cohort (ranges, N=104-164): mean age, 46.9 years- (AD monotherapy group, 42.6 years – adjunctive gabapentin group, 52.7); female, 74.8% (ECT group, 64.3% - adjunctive gabapentin group, 76.3); severe MDD, 35.1% (adjunctive bupropion, 26.5% – ECT group, 88.6%); suicidal ideation, 3.6% Use of Specialized Mental Health Services and Outpatient Care 77.6% of patients had ≥1 psychotherapy visits and 82.9% had a psychiatrist visit in the 6-month pre-index period in the SPRAVATO cohort, compared to 41.4% and 34.2% of patients in the TRD conventional therapies cohort. The proportion of patients with ≥1 outpatient visit for MDD was 91.9% in the SPRAVATO cohort and 63.6% in the TRD conventional therapies cohort. Healthcare Resource Utilization Pre-index all-cause inpatient admissions and ED visits were identified in 13% and 27.6% of the SPRAVATO cohort and 10.6% and 30.8% of the TRD conventional therapies cohort. Pre-index mental health–related inpatient admissions and ED visits were identified in 12.2% and 16.3% of the SPRAVATO cohort and in 8.2% and 10.3% of the TRD conventional therapies cohort. Healthcare Costs The mean all-cause total healthcare cost over the 6month pre-index period was $2532 in the SPRAVATO cohort and $1873 in the TRD conventional therapies cohort (ranged from $923, AD monotherapy cohort, to $5063, ECT cohort). In the SPRAVATO cohort, 58.2% of all-cause total healthcare costs were mental health–related ($1473), while this ranged from 25.2% ($724, adjunctive gabapentin cohort) to 69.8% ($3532, ECT) in the TRD conventional therapies cohort.
Teeple A, Zhdanava M, Pilon D, et al. Access and real-world use patterns of esketamine nasal spray among patients with treatment-resistant depression covered by private or public insurance. Curr Med Res Opin. 2023;39(8):1167-1174. doi:10.1080/03007995.2023.2239045
A retrospective study evaluating access and real-world use patterns of SPRAVATO in adult patients with TRD with private or public insurance3 Data Source: Clarivate’s Real World Data Repository (01/2016-03/2021) Inclusion Criteria: ≥1 pharmacy or medical claim for SPRAVATO; evidence of TRD during MDE in which SPRAVATO was initiated and before or on the date of the first esketamine claim; ≥1 diagnosis for MDD during the MDE in which esketamine was initiated); ≥18 years of age as of the index date; ≥6 months continuous clinical activity before index date (date of SPRAVATO initiation)	Patient Characteristics A total of 273 patients were initiated on SPRAVATO. Mean age was 49.3 years, 66.3% were female, 80.2% were covered by commercial insurance, 11.0% by Medicare, 5.9% by Medicaid, and 2.9% by another type of insurance. The mean time from evidence of TRD to the index date was 27.6 months, and the mean time from the start of the MDE in which SPRAVATO was initiated to index date was 58.2 months. Mean number of AD treatment courses was 2.1 since evidence of TRD and 4.0 since the start of the MDE. 66.3% of patients had ≥1 observed mental health-related outpatient visit during the baseline period. Number of SPRAVATO Treatment Sessions Among Patients Who Initiated SPRAVATO Over a mean (SD) of 11.8 (6.4) months postindex, patients had a mean (SD) of 11.8 (13.8) SPRAVATO treatment sessions. The proportion of patients with ≥8 SPRAVATO treatment sessions (per label, 8 sessions correspond to the induction phase) was 47.6%, 43.2% initiated maintenance phase (≥9 SPRAVATO sessions), and 34.8% had ≥12 SPRAVATO sessions. 78.0% of patients initiated SPRAVATO 56 mg, which is the recommended starting dose per USPI. 87.4% of patients received SPRAVATO 84 mg by the 12th session. Mean (SD) time from the index to the eighth session (induction period) was 80.1 (71.9) days. Per label, induction phase is 28 days with twice weekly administration. Median time between treatment sessions during induction was 7-8 days. Access Among patients for whom the first SPRAVATO claim was a pharmacy claim (N=534), 34.6% of claims were approved, 46.3% were rejected, and 19.1% were abandoned. The main reasons for rejection were due to no coverage (57.1%), claim error (52.6%), and PA required (22.7%). Approval rate increased to 85.2% for SPRAVATO by the second session and remained stable. 16.2% of those receiving a rejection on the first SPRAVATO claim, eventually received approval for a newly submitted SPRAVATO claim. Mean time between first submitting a pharmacy claim and final decision was 7 days and 1.3 days for first and second SPRAVATO treatment sessions, respectively.
Joshi K, Pilon D, Shah A, et al. Treatment patterns, healthcare utilization, and costs of patients with treatment-resistant depression initiated on esketamine intranasal spray and covered by US commercial health plans. J Med Econ. 2023;26(1):422-429. doi:10.1080/13696998.2023.2188845
A retrospective study evaluating real-world treatment patterns and healthcare outcomes of commercially insured adult patients with TRD who initiate SPRAVATO including patients with comorbid conditions6 Data Source: IBM® MarketScan® Commercial and Medicare Supplemental Databases (01/2015-10/2020) Inclusion Criteria: ≥1 pharmacy or medical claim for SPRAVATO; evidence of TRD during the MDE in which SPRAVATO was initiated and before or on the date of the first esketamine claim (index date); ≥1 diagnosis for MDD during the MDE in which SPRAVATO was initiated; ≥6 months of continuous insurance eligibility before and after the index date; ≥18 years of age as of the index date; for patients in the comorbidity subgroups- ≥1 claim of metabolic or cardiovascular conditions, pain, anxiety disorder, or SUD. Exclusion Criteria: ≥1 pharmacy or medical claim for SPRAVATO before 3/5/2019 or before evidence of TRD	A total of 269 patients were in the TRD cohort. Comorbidity subgroups included: 123 with comorbid cardiometabolic condition 144 with comorbid pain condition 189 with comorbid anxiety disorder condition 58 with comorbid SUD SPRAVATO Treatment Patterns Mean (median) number of SPRAVATO treatment sessions during 6-month follow-up period: TRD cohort: 11 (10) Comorbid subgroup range: 11 (9) (cardiometabolic subgroup) to 13 (11) (SUD subgroup) Mean (median) time (days) to complete 8 sessions: TRD cohort: 56.9 (38.0) Comorbid subgroup range: 54.8 (36.0) (anxiety disorder subgroup) to 63.6 (44.0) (SUD subgroup) Median number of days between sessions during the induction phase: TRD and subgroups range: 5 to 8 days Mean (median) time (days) from the 9th to the 12th session: TRD cohort: 24.0 (21.0) Comorbid subgroup range: 22.1 (21.0) (cardiometabolic subgroup) to 24.5 (21.0) (pain subgroup) Median number of days between sessions during the first maintenance phase ranged from 6 to 8 days among the TRD cohort and subgroup. Proportion of patients on 84 mg dose by the 12th session: TRD cohort: 88.1% Cardiometabolic subgroup: 91.1% Pain subgroup: 87.5% Anxiety subgroup: 83.8% SUD subgroup: 96.0% Proportion of patients with ≥8 (induction phase) and ≥12 SPRAVATO treatment sessions (first maintenance phase), respectively: TRD cohort: 61.3%, 40.5% Cardiometabolic subgroup: 60.2%, 36.6% Pain subgroup: 68.8%, 44.4% Anxiety disorder subgroup: 64.0%, 42.3% SUD subgroup: 72.4%, 43.1% Mean acute care costs per-patient during the 6month pre- and post-SPRAVATO periods, respectively, in 2020 USD: TRD cohort: $5565, $5688 Cardiometabolic subgroup: $8239, $6284 Pain subgroup: $7988, $5831 Anxiety disorder subgroup: $7726, $6506 SUD subgroup: $11,383, $9978 Mean inpatient MH costs per-patient during the 6-month pre- and post-SPRAVATO periods, respectively, in 2020 USD: TRD cohort: $3480, $3262 Cardiometabolic subgroup: $4864, $2792 Pain subgroup: $4398, $2731 Anxiety disorder subgroup: $4915, $3644 SUD subgroup: $8441, $8910 Mean outpatient costs generally trended higher in the post-SPRAVATO initiation period than pre-initiation for all cohorts, while mean healthcare resource utilization generally trended lower. Mean number of MH ED visits per 100 patients during the 6-month pre- and post-SPRAVATO periods, respectively: TRD cohort: 31.6, 19.7 Cardiometabolic subgroup: 48.0, 22.8 Pain subgroup: 47.9, 21.5 Anxiety disorder subgroup: 40.2, 23.8 SUD subgroup: 58.6, 32.8
Liberman J, Pesa J, Rui P, et al. 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. Medicine (Baltimore). 2023;102(7):e32895. doi:10.1097/MD.0000000000032895
A retrospective observational cohort to measure the association of social determinants of health and distance to a certified treatment center with completion of the induction phase (8 administrations of SPRAVATO within 45 days of initiation) and 6month persistence (defined as continuous use without a >60-day gap) to SPRAVATO.7 Social determinants included employment, income, education, health insurance coverage, population density, and race/ethnicity. Data Source: Clarivate’s medical and pharmacy claims (10/11/2019-12/31/2020) Inclusion Criteria: ≥1 pharmacy or medical claim for SPRAVATO; ≥18 years of age at initiation of SPRAVATO; ≥1 medical or pharmacy claim in each quarter of the 12-month baseline and 6-month follow-up period; residence within reasonable distance of a certified treatment center. Exclusion Criteria: ICD-10 diagnosis of bipolar disorder, schizoaffective disorder, or schizophrenia.	Patient Characteristics A total of 308 patients initiating SPRAVATO and 1540 controls were included in the analysis to assess completion of the induction phase; there were no statistically significant differences between SPRAVATO initiators and controls. Of patients initiating SPRAVATO, 275 patients with no evidence of MDSI (probable TRD) were appropriate to continue to the persistence analysis (maintenance phase). SPRAVATO initiators had mean age of 48.8 years (SD: 16.9 years), mostly female (61.4%), and commercially insured (57.8%). Average (SD) distance to a certified treatment center was 7.0 (9.4) miles. Initiation Distance >7.2 miles away from the closest treatment center (OR: 0.75; 95% CI: 0.56-0.99), percent of the population non-Hispanic African American (OR: 0.58; 95% CI: 0.43-0.78), percent of the population Hispanic (OR: 0.40; 95% CI: 0.28-0.58) and living in rural areas (OR: 0.64; 95% CI: 0.44-0.94) were associated with lower odds of initiation. Higher population density (OR: 2.12; 95% CI: 1.40-3.22), percent of population Asian NHOPI (OR: 3.19; 95% CI: 2.23-4.56), mental health providers per 100,000 population (OR: 1.55; 95% CI: 1.09-2.19), and PCPs per 100,000 population (OR: 1.55; 95% CI: 1.12-2.16) were associated with higher odds of SPRAVATO initiation. Factors Associated with Completion of Induction Phase A total of 133/308 (43.2%) patients completed the induction phase. After adjustment, substance use disorder (OR: 2.67; 95% CI: 1.08-6.63) and CCI (OR: 1.73; 95% CI: 1.12-2.66) were positively associated with higher odds of not completing the induction phase. Baseline history of psychiatric medication use (OR: 0.54; 95% CI: 0.32-0.90) and residing in counties above the median level of high school graduation rate (OR: 0.53; 95% CI: 0.32-0.89), unemployment rate (OR: 0.43; 95% CI: 0.25-0.74), and PCPs per 100,000 (OR: 0.41; 95% CI: 0.24-0.69), were negatively associated with higher odds of not completing the induction phase. Factors Associated with Treatment Discontinuation in Patients with Probable TRD Patients who traveled >7.2 miles to a treatment center were significantly less likely to remain on therapy (25.2% vs 36.8%; P=0.02) through the 6-month follow-up period. Notable discontinuation occurred after the first 25 days. Higher percent Asian (HR: 1.37; 95% CI: 1.01-1.87), and CCI (1.26; 95% CI: 1.08-1.48) were also associated with higher discontinuation rate. Higher unemployment rate (HR: 0.61, 95% CI: 0.45-0.83), higher high school graduation rate (HR: 0.69; 95% CI: 0.51-0.94), higher PCPs per 100,000 population (HR: 0.69, 95% CI: 0.50-0.95), baseline psychiatry visits (HR: 0.55; 95% CI: 0.40-0.76), and baseline psychiatric medication use (HR: 0.73; 95% CI: 0.54-1.00), were associated with lower discontinuation rate.
Teeple A, Zhdanava M, Pilon D, et al. Esketamine use among patients with treatment-resistant depression initiating esketamine and completing induction in the United States. Poster Presented at the Psych Congress; September 17-20, 2022; New Orleans, LA.
A retrospective study describing real-world characteristics and SPRAVATO use patterns among US adults with TRD who completed induction with SPRAVATO8 Data Source: Provider-based open claims database that collects and links information from pharmacy and clinical networks from 01/2016-03/2021 Inclusion Criteria: ≥1 SPRAVATO pharmacy/medical claim Evidence of TRD ≥1 diagnosis for MDD ≥6 months of continuous clinical activity before index date ≥18 years old as of index date ≥6 weeks of continuous clinical activity after index date, and completion of ≥8 SPRAVATO sessions within the first 6 weeks of follow-up A 6-week interval was chosen since claims may misalign with treatment sessions. Index Date: date SPRAVATO initiated Baseline Period: 6-month before index date Follow-up Period: The earlier of either end of continuous clinical activity or available data	SPRAVATO Use Patterns Among 273 patients who initiated SPRAVATO, 48 (17.6%) completed 8 treatment sessions within 6 weeks. Mean number of SPRAVATO treatment sessions was 24.4 with a mean length of follow-up of 10.9 months. 93.8% continued treatment after induction, 22.9% had 9-12 sessions, and 70.8% had ≥13 sessions during the follow-up period. Dosage of SPRAVATO Used for Treatment Sessions Most patients (95.8%) started with the recommended starting dose per label (56 mg). By the end of induction, 81.3% of patients titrated up to 84 mg and 91.9% titrated up to 84 mg by the 12th treatment session. Time Between Consecutive SPRAVATO Treatment Sessions Mean (median) time to complete induction was 28.2 (27.0) days. Mean frequency of SPRAVATO sessions was every 3.5 to 4.5 days during induction, 7.0 to 7.8 days between the 9thand 12th sessions, and 17.2 days after the 13th session.
Zhdanava M, Joshi K, Shah A, et al. Understanding profiles of patients with treatment-resistant depression by stringency of health plan prior authorization criteria for approval of esketamine. Presented at Psych Congress; September 6-10, 2023; Nashville, TN.
A retrospective study characterizing patients with TRD initiated on SPRAVATO through a US health plan with varying coverage based on PA criteria9 Data Source: Symphony Health, an ICON plc Company, PatientSource® data (March 2016-February 2022) was used. This captures >75% of all US retail prescription claims across multiple payer channels (i.e., commercial, Medicare, Medicaid). Inclusion Criteria: ≥1 claim for SPRAVATO with the first claim during the intake period, ≥12 months of clinical activity before the index date, ≥18 years old, Evidence of TRD before the index date, defined as ≥2 unique AD treatment courses of adequate dose and duration within the same MDE as the index date, ≥1 ICD-10 diagnosis for MDD during the MDE in which SPRAVATO was initiated Cohort Classification: Stringent cohort: patients with health plan requiring (PA) higher than label requirement to initiate SPRAVATO (i.e., requiring failure of ≥3 Ads) Nonstringent cohort: patients with health plan PA criteria same as label (requiring failure of ≥2 Ads) or less than label (no PA)	Patient Characteristics A total of 168 patients were in the stringent cohort and 400 patients were included in the nonstringent cohort. 66.7% and 63.3% in the stringent and nonstringent cohort, respectively, had commercial insurance. AD Treatment Courses Before SPRAVATO Initiation Duration of MDE (mean [median]) before SPRAVATO initiation was similar in the stringent cohort (51.2 [55.4] months) and the nonstringent cohort (49.8 [55.2] months). Time from evidence of TRD to SPRAVATO initiation was also similar between cohorts (22.1 [20.3] months in the stringent cohort and 20.6 [18.7] months in the nonstringent cohort). Patients completed 3.9 (4.0) and 3.8 (3.0) unique AD treatment courses during their current MDE in the stringent and nonstringent cohorts, respectively. Since evidence of TRD, patients completed 2.0 (2.0) and 1.9 (1.0) unique AD treatment courses in the stringent and nonstringent cohorts, respectively. Around 95% and over 76% of patients in both cohorts used augmentation therapy during current MDE and since evidence of TRD, respectively. Around 59% and 50% of patients in both cohorts augmented with second-generation antipsychotics during current MDE and since evidence of TRD, respectively. Nonpharmacological therapy (i.e., psychotherapy, TMS, or ECT) was used by 44% of patients in the stringent cohort and 35% of patients in the nonstringent cohort during the baseline period.
Clemens K, Zhdanava M, Teeple A, et al. Understanding patient profiles among Medicaid patients with treatment-resistant depression initiated on esketamine. Presented at Psych Congress; September 6-10, 2023; Nashville, TN.
A retrospective study describing characteristics and SPRAVATO treatment patterns among newly initiated SPRAVATO treatment in Medicaid beneficiaries10 Data Source: de-identified claims data from Merative™ MarketScan® Multi-State Medicaid Database, which includes multiple states that are not disclosed and cannot be differentiated (January 1, 2016, to June 30, 2022) Inclusion Criteria: ≥1 claim for SPRAVATO, Evidence of TRD before or on the index date, ≥18 years old, ≥12 months of continuous insurance eligibility before index date, ≥1 ICD-10 diagnosis of MDD, absence of bipolar disorder, psychosis, schizophrenia, schizoaffective disorder, or other non–mood-related psychotic disorders during the baseline period	Patient Characteristics 151 patients were included. Average age was 40.6 years, 70.2% were female, and 58.3% were White. 62.3% of patients had ≥3 unique AD claims and 25.2% had ≥4 unique AD claims; 54.3% of patients had claims for antipsychotics. 81.5% had anxiety disorders, 30.5% had substance-related and addictive disorders, and 20.5% had evidence of suicidal ideation or probable attempt. Mean follow-up period was 13.2 months, and patients had, on average, 22.5 SPRAVATO sessions. SPRAVATO Use 67.5% of patients completed ≥8 sessions (induction dosing), and half of those patients completed within 30.5 days (28 days recommended per label). The median time between SPRAVATO treatment sessions was longer than recommended per label (4-5 days vs 3.5 days) in the induction phase and per label during the maintenance phase (7 days). <30% of patients initiated SPRAVATO 84 mg on the index date but >75% of patients who completed induction were on SPRAVATO 84 mg. 61.6% of patients received SPRAVATO through pharmacy benefits and 45.7% received SPRAVATO through medical benefits.
Joshi K, Zhdanava M, Shah A, et al. Treatment patterns, acute care healthcare resource use, and costs of patients with treatment-resistant depression completing induction phase of esketamine in commercial and Medicare Advantage plans. Presented at the American Society of Clinical Psychopharmacology (ASCP) Annual Meeting; May 30-June 2, 2023; Miami Beach, FL.
A retrospective study describing treatment patterns, acute healthcare use, and costs among adults with TRD who completed induction treatment with SPRAVATO in the US.11 Data Source: Optum de-identified Clinformatics® Data Mart Database (January 2016 to June 2022) Intake Period: March 5, 2019 (esketamine approval date for TRD in the United States) to June 30, 2022 Index Date: date of first SPRAVATO claim Baseline Period: 12 months before the index date Follow-up Period: spanned the index date until the earliest of end of data availability or continuous health plan eligibility Inclusion Criteria: first SPRAVATO claim during intake period, at least 8 SPRAVATO sessions, 18 years or older, at least 12 months of continuous insurance eligibility and evidence of TRD prior to index date, at least 1 claim of MDD within the same MDE as the index date Study Populations: induction completer cohort and a subgroup of patients with at least 1 MH-related acute healthcare visit during the baseline period (prior acute healthcare user cohort)	Patient Characteristics Induction completer cohort: 322 patients, 62.1% female, 79.5% White, 72% commercially insured, 15.1 months mean follow-up Prior acute healthcare user cohort: 111 patients, 69.4% female, 76.6% White, 73.9% commercially insured, 16.1 months mean follow-up SPRAVATO Use Induction completer cohort: mean of 23.1 SPRAVATO treatment sessions during follow-up; mean (median) time to complete induction was 73.2 (40.5) days (28 days per USPI); 75.2% of patients completed ≥4 maintenance sessions Prior acute healthcare user cohort: mean of 22.0 SPRAVATO treatment sessions during follow-up; mean (median) time to complete induction was 78.8 (40.0) days (28 days per USPI); 73.9% of patients completed ≥4 maintenance sessions Follow-up Treatment Patterns Both cohorts claimed 2 (median) unique ADs during follow-up period. 28.6% and 36.0% in the induction completer and the subgroup with prior acute healthcare use, respectively, claimed ≥3 Ads. More than 75% of patients received psychotherapy during the follow-up period. Acute Healthcare Costs and Resource Use Mean all-cause acute healthcare costs PPPM were $69 and $899 lower in the follow-up period compared to baseline in the induction completer and prior acute healthcare user cohort, respectively. Similar reductions were seen in the MH-related costs. See Figure: All-Cause and MH-Related Acute Care Costs at Baseline and During the Follow-up Period. All-cause and MH acute healthcare resource use remained similar in the induction completer cohort. All-cause acute healthcare resource use decreased in the prior acute healthcare user cohort: 0.64 and 0.46 IP days and 0.26 and 0.24 ED visits PPPM at baseline and during the follow-up period, respectively. Mental health-related acute resource use in the prior acute healthcare user cohort decreased: 0.63 and 0.44 IP days, and 0.12 and 0.14 ED visits PPPM at baseline and during the follow-up period, respectively. Figure: All-Cause and MH-Related Acute Care Costs at Baseline and During the Follow-up Period
Clemens K, Zhdanava M, Teeple A, et al. Treatment patterns and persistence among patients with treatment-resistant depression initiated on esketamine nasal spray. Poster presented at Psych Congress Elevate; May 30-June 2, 2024; Las Vegas, NV.
Real-world, retrospective, observational cohort study in the US of the use and persistence of treatment with SPRAVATO in patients with TRD.4 Data Source: de-identified closed health insurance claims data from Komodo Research Database and PHQ-9 scores from Komodo Clinical Observations Database (01/2016-06/2023) Index Date: date of first SPRAVATO claim Baseline Period: 12 months prior to the index date Follow-up Period: index date to date of final data availability or end of continuous healthcare insurance eligibility Inclusion criteria: Adults with ≥1 diagnosis of MDD and evidence of TRD before the index date who initiated SPRAVATO treatment during the intake period (03/05/2019-end of data). Patients were expected to have ≥1 PHQ-9 score(s) during the baseline period or on the index date and during the follow-up period while still on SPRAVATO treatment.	Patient Characteristics A total of 103 patients were included (mean age at index date, 41.5 years; female, 65.0%; commercially insured, 68.9%). SPRAVATO Use Patients completed a mean (median) of 21.7 (15.0) sessions of SPRAVATO during a mean (median) follow-up period of 15.7 (12.8) months. Overall, 70.9% of patients completed the induction phase; half of these patients completed induction within 64 days (which was beyond the 28 days specified in the label). Overall, 61.2% of patients completed ≥12 treatment sessions (8 induction sessions + ≥4 maintenance sessions) The median frequency of sessions during induction was lower than that recommended in the label (7-9 days vs 3.5 days, respectively) The median frequency of the first 4 maintenance sessions was comparable to that recommended in the label (7-8 days vs 7 days, respectively). In the first treatment session, 64.1% and 35.9% of patients received SPRAVATO 56 mg and 84 mg doses, respectively. By the end of induction, these percentages were 20.5% (56 mg) and 79.5% (84 mg), respectively. Persistence on SPRAVATO Treatment Overall, 50% of patients persisted on SPRAVATO treatment for 8.2 months. The Kaplan-Meier rate of persistence was 61.7% at 6 months and 32.0% at 12 months.
Major Depressive Disorder with Acute Suicidal Ideation or Behavior
Zhdanava M, Teeple A, Pilon D, et al. 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. J Med Econ. 2023;26(1):691-700. doi:10.1080/13696998.2023.2208993
Retrospective observational cohort study to evaluate real-world SPRAVATO use, access, and (HRU) after initiating SPRAVATO in patients with MDSI. HRU and costs (2021 USD) were described over 6 months pre-index and 6 months postindex.12 Data Source: Clarivate’s Real World Data (01/201603/2021) Cohorts: MDSI overall cohort- Patients with MDSI initiated SPRAVATO on or after 03/05/2019 (SPRAVATO approval for TRD) 2020-initiatior subgroup- patients with MDSI initiating SPRAVATO on or after 08/05/2020 (SPRAVATO approval for MDSI) Inclusion Criteria: ≥1 pharmacy or medical claim for SPRAVATO (first claim during the intake period); ≥12 months of continuous clinical activity before the date of SPRAVATO initiation; evidence of MDSI (≥1 code for either suicidal ideation or behavior and ≥1 claim with an MDD diagnosis) prior to the date of SPRAVATO initiation; ≥18 years of age on the date of SPRAVATO initiation. Exclusion Criteria: initiation of SPRAVATO before evidence of MDSI or initiation of SPRAVATO prior to March 5, 2019; ≥1 claim with a diagnosis for schizophrenia spectrum or another psychotic disorder during the baseline period.	Patient Characteristics A total of 269 patients in the overall MDSI cohort and 78 patients in the 2020-initiator subgroup (treatment with SPRAVATO after its approval for MDSI) had a pharmacy claim for SPRAVATO. A total of 169 patients and 47 patients in the overall MDSI cohort and 2020-initiaitor subgroup were initiated on SPRAVATO (≥1 approved pharmacy/medical claim). Mean age was 40.9 and 37.7 years, 62.1% and 63.8% were female, 88.2% and 87.2% were commercially insured, and 99.4% and 97.9% had a diagnosis of suicidal ideation or behavior during the baseline period in the overall and 2020-initiator cohort, respectively. Access to SPRAVATO When the first SPRAVATO claim was a pharmacy claim, 46.8% and 39.7% had a claim approval, 38.7% and 47.4% had a rejected claim, and 14.5% and 12.8% had an abandoned claim in the overall MDSI cohort a in the 2020-initiator subgroup, respectively. The main reasons for claim rejection in the overall cohort and 2020-initiator subgroup were “claim error” (52.9% and 54.1%, respectively), “not covered by plan” (52.9% and 45.9%, respectively), and “prior authorization required” (26.9% and 37.8%, respectively). The approval rate for SPRAVATO increased to 90.7% and 81.3% by session 8 in the overall MDSI cohort and the 2020-initiatior subgroup, respectively. The mean (median) number of attempts at submitting an SPRAVATO prescription for insurance approval was 4.8 (3.0) in the overall MDSI cohort (mean time: 7.9 days) and 4.0 (3.0) in the 2020-initiator subgroup (mean time: 8.7 days) for the first SPRAVATO session. The mean number of attempts decreased to 2.0 and 1.5 by the eighth session. AD Use During the Follow-up Period (After Initiation of SPRAVATO) 39.6% and 36.2% of patients had at least 1 unique AD claim in the overall MDSI cohort and 2020-initiator subgroup, respectively. Specialized Mental Health Service Use During the Follow-up Period (After Initiation of SPRAVATO): 37.9% and 27.7% of patients had a psychotherapy visit, in the overall MDSI cohort and 2020-initiator subgroup, respectively. 16.6% of patients in the overall MDSI cohort and 8.5% of patients in the 2020-initiator subgroup received a psychiatric diagnostic evaluation. 7.7% of patients in the overall MDSI cohort and 2.1% of patients in the 2020-initiator subgroup received care in an inpatient psychiatric facility. Number of SPRAVATO Treatment Sessions The mean (median) number of SPRAVATO treatment sessions was 11.1 (6.0) in the overall cohort compared to 7.9 (4.0) in the 2020-initiator subgroup. In the overall MDSI cohort 45.5% of patients had ≥8 SPRAVATO sessions compared with 38.3% of patients in the 2020-initiator subgroup. The mean (median) time from SPRAVATO initiation to the eighth session was 85.0 (58.5) days in the overall MDSI cohort and 50.8 (49.0) days in the 2020-initiator subgroup. Per USPI, treatment of MDSI with SPRAVATO is dosed twice weekly for 4 weeks (28 days). Severity of Depressive Symptoms in the 6-Month Subgroup Of 169 patients receiving SPRAVATO, 115 (68%) had at least 6 months of follow-up. Mean age was 42 years and 62.5% were female. Severity of symptoms- 67.8% of patients had ≥1 diagnosis for MDD and 76.9% and 60.3% of these patients had severe MDD in the pre and post index periods, respectively. HRU, and Healthcare Costs in the 6-Month Subgroup ≥1 all-cause hospitalization: pre-index period, 37%; postindex, 19.1% ≥1 all-cause ER visit: pre-index period, 42.6%; postindex, 33.9% ≥1 all-cause outpatient visit: pre-index period, 92.2%; postindex, 81.7% All-cause per patient per member (PPPM) Healthcare Costs, total mean±SD (median): 6 months pre-index: $8371±$15,792 ($3475) 6 months postindex: $6486±$7614 ($3906) All-cause PPPM medical healthcare charges, total mean±SD (median): 6 months pre-index: $8252±$15,770 ($3188) Outpatient charges: $4439±$11,786 ($1313) Inpatient charges: $2507±$5655 ($0) 6 months postindex: $4733±$7505 ($1652) Outpatient charges: $2570±$4610 ($1006)) Inpatient charges: $1188±$4096 ($0) Sensitivity Analysis: HRU and Healthcare Costs in the 1-Month Subgroup Of 169 patients receiving SPRAVATO, 155 (91.7%) had at least 1 month of follow-up. ≥1 all-cause hospitalization: pre-index period, 11.0%; postindex, 3.2% ≥1 all-cause outpatient visit: pre-index period, 62.6%; postindex, 58.1% All-cause PPPM healthcare costs, total mean±SD (median): 1 month pre-index: $6941±$15,346 ($918)  1 month postindex: $8546±$10,622 ($6499)  All-cause PPPM medical healthcare charges, total mean±SD (median): 1 month pre-index: $6786±$15,330 ($748) 1 month postindex: $5007±$10,754 ($1750)
Teeple A, Zhdanava M, Pilon D, et al. Treatment patterns among patients with major depressive disorder and acute suicidal ideation or behavior initiated on esketamine or traditional therapies in the United States. Poster Presented at the Psych Congress; September 17-20, 2022; New Orleans, LA.
A retrospective study describing treatment patterns among patients with MDSI initiated on SPRAVATO or traditional MDD therapies13 Data Source: IBM® MarketScan® Commercial Database (01/2016-01/2022) Inclusion Criteria: -≥1 pharmacy or medical claim for SPRAVATO on or after 08/05/2020 OR ≥1 claim for ECT, an AD with AP, or an AD in monotherapy with no evidence of index therapy in the 12-month baseline period and no claims for SPRAVATO at any time -Evidence of MDSI on or before the index date -≥12 months of continuous health plan eligibility before index date -≥18 years old on the index date Index Date: date of SPRAVATO or other traditional therapy initiation Baseline Period: 12 months before the index date Follow-up Period: from index date until end of data availability or end of continuous health insurance eligibility	Patient Characteristics A total of 122, 336, 9958, and 4496 patients were included in the SPRAVATO, ECT, AP augmentation, and AD monotherapy cohorts, respectively. Number of SPRAVATO Treatment Sessions The mean (median) number of treatment sessions was 10.9 (8.0). The mean (median) duration was 6.5 (6.6) months. Over half of the SPRAVATO cohort (51.6%) completed 8 sessions for the treatment of MDSI per label, but the intervals between sessions and mean time to completion of 8 sessions (56.5 days) exceeded the per-label recommendation. Patients completing ≥9 sessions were 45.9%. Over half of the SPRAVATO cohort (59%) demonstrated evidence of TRD, which may explain continuation of SPRAVATO treatment beyond the 8 sessions. AD Treatment Patients with ≥1 claim for an AD in the SPRAVATO, ECT, AP augmentation, and AD monotherapy cohorts: 82%, 85%, 94%, and 100%, respectively Patients with ≥3 unique AD agent claims in the SPRAVATO, ECT, AP augmentation, and AD monotherapy cohorts: 20%, 31%, 21%, and 5%, respectively Psychotherapy 79%, 72%, 64%, and 48% of patients were treated with psychotherapy in the SPRAVATO, ECT, AP augmentation, and AD monotherapy cohorts, respectively.
Teeple A, Zhdanava M, Pilon D, et al. Characteristics of patients with major depressive disorder and acute suicidal ideation or behavior initiated on esketamine or traditional therapies in the United States. Poster Presented at the Psych Congress; September 17-20, 2022; New Orleans, LA.
A retrospective study describing characteristics, HRU, and healthcare costs among patients with MDSI before and after SPRAVATO or other therapy initiation5 Data Source: IBM® MarketScan® Commercial Database (01/2016-01/2022) Inclusion Criteria: -≥1 pharmacy or medical claim for SPRAVATO on or after 08/05/2020 OR ≥1 claim for ECT, an AD with AP, or an AD in monotherapy with no evidence of index therapy in the 12-month baseline period and no claims for SPRAVATO at any time -Evidence of MDSI on or before the index date -≥12 months of continuous health plan eligibility before index date -≥18 years old on the index date Index Date: date SPRAVATO or other traditional therapy initiated Baseline Period: 12 months before index date Follow-up Period: From index date until end of continuous healthcare insurance eligibility or data availability	Patient Characteristics A total of 122, 336, 9958, and 4496 patients were included in the SPRAVATO, ECT, AP augmentation, and AD monotherapy cohorts, respectively. Prior to index treatment initiation, 59.0%, 44.6%, 27.3%, and 2.8% in the SPRAVATO, ECT, AP augmentation, and AD monotherapy cohorts, respectively had evidence of TRD. During baseline period, 93%, 91%, 89%, and 32% had ≥1 AD claim and 88%, 82%, 67%, and 44% had ≥1 psychotherapy claims in the SPRAVATO, ECT, AP augmentation, and AD monotherapy cohorts, respectively. HRU and Healthcare Costs During follow-up, the ECT cohort had the highest mean acute care HRU (3.17 inpatient and ED days combined), followed by the AP augmentation cohort (0.92 days), the SPRAVATO cohort (0.59 days), and the AD monotherapy cohort (0.32 days). Mean all-cause medical costs were also highest in the ECT cohort ($4624), followed by the AP augmentation cohort ($2163), the SPRAVATO cohort ($1869), and the AD monotherapy cohort ($863). Note: medical costs were from a private payer’s perspective and included inpatient costs, ED costs, and outpatient costs. Costs excluded costs of index treatments, durable medical equipment, and dental/vision care. Compared to baseline, SPRAVATO had the largest decrease in mean acute care HRU and mean medical costs (58% and 50%, respectively) compared with the other cohorts.
Abbreviations: AD, antidepressant; AP, antipsychotic; CCAE, Commercial Claims and Encounters; CI, confidence interval; CCI, Charlson comorbidity index; ECT, electroconvulsive therapy; ED, emergency department; HCP, healthcare professional; HR, hazard ratio; HRU, healthcare resource utilization; ICD-10, International Classification of Diseases, Tenth Revision; MD, mean difference; MDD, major depressive disorder; MDE; major depressive episode; MDCD; Multi-State Medicaid Database; MDSI, major depressive disorder with suicidal ideation; MH, mental health; NHOPI, Native Hawaiian, and Other Pacific Islander; OR, odds ratio; PA, prior authorization; PCP, primary care physician; PHQ-9, 9-item Patient Health Questionnaire; PPPM, per patient per month; QUE, Quetiapine; SD, standard deviation; SMD, standardized mean difference; SUD, substance use disorder; TMS, transcranial magnetic stimulation; TRD, treatment-resistant depression; USPI, United States Prescribing Information; WPL, work productivity loss; WPAI, Work Productivity and Activity Impairment.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 09 October 2024.