Treatment-resistant depression (TRD) is commonly defined as non-response to ≥2 antidepressant treatment courses of adequate doses and durations in the current episode in patients with major depressive disorder (MDD). Esketamine (ESK) nasal spray was approved by the Food and Drug Administration in March 2019 for the treatment of TRD in adults in conjunction with an oral antidepressant (AD). This study assessed changes in depressive symptoms following ESK initiation among patients with TRD in a real-world setting.

The study was a retrospective longitudinal observational cohort study of adults with TRD who initiated esketamine treatment between March 2019 and June 2022. Data were sourced from the PremiOM™ MDD Dataset (OM1, Boston, MA), a continuously updated cohort of over 440,000 patients with MDD in the United States with linked claims and electronic medical record data. Patients were classified as having TRD if they had ≥1 diagnosis of MDD during the 6 months prior to or on the index date (defined as ESK initiation) and a record of ≥2 unique ADs of adequate dose and duration at any time prior to the index date within the same major depressive episode (MDE; defined as no clean period of ≥180 days without ADs and/or MDD diagnoses). The Patient Health Questionnaire-9 (PHQ-9) was used to measure depressive symptoms. A machine learning model was used to estimate PHQ-9 scores for patients with no documented scores. The latest PHQ-9 score among questionnaires administered in the six months prior to or on the date of first ESK treatment was used as the baseline score. Baseline scores were compared to the latest scores in the 0-3-month and 3-6 month windows after first ESK treatment. A sensitivity analysis excluding the estimated scores was conducted. Marginal models were used to test for differences in post-treatment scores relative to baseline.

The study cohort included 163 patients with a mean age of 49.5 years (standard deviation [SD]=15.4). Most patients were female (58.3%). At baseline, the mean PHQ-9 score was 15.0 (SD=6.7) and 55.8% of patients had either moderately severe or severe depression (PHQ-9 ≥15). Patients experienced statistically significant reductions in PHQ-9 scores of 2.9 points (95% CI: 1.7 to 4.1, p<0.001) in the 0–3-month interval and 4.4 points (95% CI: 3.2 to 5.6, p<0.001) in the 3–6-month interval relative to baseline. The percentage of patients with moderately severe or severe depression (PHQ-9 ≥15) decreased to 34.4% at the 0-3 month interval and 20.9% at the 3-6 month interval. Results were consistent when estimated PHQ-9 scores were excluded.

Among patients with TRD in a real-world setting, PHQ-9 scores significantly decreased in the 6 months following initiation of ESK treatment. Further investigation of longer-term effectiveness of ESK and among key subgroups is warranted.

Janssen Pharmaceuticals, the manufacturer of esketamine

Major depressive disorder (MDD) is the second leading cause of disability in the US, and increases the risk of poor health outcomes. This analysis assessed the real-world benefit and availability of esketamine for patients with difficult-to-treat MDD.

Data were drawn from the Adelphi Real World Depression Disease Specific Programme XII (DSPTM), a cross-sectional retrospective survey of physicians and their patients in the United States in 2022. Physicians reported details for patients with MDD receiving esketamine regarding their prescribed medication (including access), daily functioning and disease improvement whilst receiving esketamine (reported by Clinical Global Impression Improvement Scale (CGI-I)),)) change in depression severity (reported by Clinical Global Impression Severity Scale (CGI-S)) and physician satisfaction. CGI-I responses measured level of disease improvement since the initiation of current depression treatment regimen (‘Very much worse=1’ to ‘Very much improved=7’). CGI-S response options were converted to numerics to measure level of severity change (‘Normal, not at all ill=0’ to ‘Among the most extremely ill patients=6’) and compared at time of esketamine initiation and currently. Physician satisfaction with medication’s ability to achieve patient treatment goals was derived from a numeric scale (where ’Not at all satisfied=1’ to ’Very satisfied=5’).

94 patients with MDD were currently receiving esketamine. Mean age was 44.3 (SD 13.26) and 47% were male. 26% of patients had been receiving esketamine for 0-3 months, 5% for 3-6 months, 15% for 6-12 months, 23% for 1-2 years and 30% for more than 2 years. CGI-I results showed physicians rated depression as improved in 98% of patients receiving esketamine >30 days. CGI-S results showed that patients receiving esketamine 1-30 days had a mean improvement of 1.2 while patients receiving esketamine for >30 days showed mean improvement of 0.9. 80% of physicians reported high satisfaction (score of 4 or 5) with esketamine’s ability to achieve patient treatment goals.

In patients receiving esketamine >30 days physicians reported that 62% could function better socially, 53% had a better quality of life, 41% had increased ability to work, 37% could better meet their own basic needs and 34% had an improvement in overall general health.

When prescribing esketamine, the treatment was only “available without restrictions” for 18% of patients, whilst 82% experienced at least some restrictions.

Physicians reported rapid and sustained clinical improvement among patients with MDD treated with esketamine in this real-world survey.

The analysis described here used data from Adelphi Real World Depression DSP. The DSP is a wholly owned Adelphi Real World product. Janssen is one of the multiple subscribers to the DSP.

Treatment resistant depression (TRD) is linked to disproportionate unemployment and productivity burden in the US. Little is known about mental-health (MH)-related disability leave and costs of patients with TRD initiated on esketamine (ESK) versus conventional therapies including transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), or antipsychotic augmentation (AP) in the US.

Adults with evidence of TRD (≥2 unique antidepressants of adequate dose and duration within the same major depressive episode) were selected from Merative™ MarketScan® Commercial and Medicare Supplemental databases (01/2016-01/2023) and classified in four cohorts (ESK, ECT, TMS, and AP) based on therapy initiated (index date) on/after 03/05/2019 (ESK approval date for TRD). Patients had ≥12 months of health plan eligibility pre-index date and disability information available pre-and post-index in the Merative™ MarketScan® Health and Productivity Management database (01/2016-12/2021). MH-related disability days (i.e., short- or long-term) and associated costs (USD 2022) were reported per-patient-per-month (PPPM) for the 6 months pre- and post-index.

The ESK cohort included 107 patients (mean age=45.5 years; female=54.2%), ECT cohort included 55 patients (mean age=47.6 years; female=41.8%), TMS cohort included 443 patients (mean age=46.1 years; female=57.3%) and AP cohort included 4,374 patients (mean age=44.8 years; female=59.1%). At month 6 pre-index, ESK cohort had a mean of 1.7 MH-related disability days PPPM relative to 1.2 days in the TMS, 1.3 days in the ECT, and 0.8 days in the AP cohort while mean MH-related disability costs were $443 PPPM in the ESK cohort relative to $178 in the ECT, $339 in the TMS, and $143 in the AP cohort.

In all cohorts, mean MH-related disability days and costs peaked at month 1 after therapy initiation followed by a decreasing trend. At month 6 post-index versus month 6 pre-index, the mean number of MH-related disability days decreased by 0.4 days PPPM in the ESK cohort, remained the same in the TMS cohort, and increased by 1.6 and 0.1 days in the ECT and AP cohorts, respectively. In the same timeframe, MH-related disability costs decreased by $312 and $123 PPPM in the ESK and TMS cohorts and increased by $353 and $26 in the ECT and AP cohorts, respectively. MH-related disability days and costs were driven primarily by short-term disability.

In this descriptive analysis, mean MH-related disability days and costs trended higher at month 6 before therapy initiation in ESK relative to TMS, ECT, and AP cohorts. ESK initiation was associated with lower mean MH-related disability days and costs at month 6 after versus before initiation. This trend was either not observed or less pronounced among patients with TRD initiated on conventional therapies. Results suggest potential economic and societal gains associated with ESK treatment for TRD.

Janssen Scientific Affairs, LLC

Disease-modifying therapies (DMTs) for Alzheimer’s disease (AD) are emerging following successful clinical trials of therapies targeting amyloid beta (Aβ) protofibrils or plaques. Determining patient eligibility and monitoring treatment efficacy and adverse events, such as Aβ-related imaging abnormalities, necessitates imaging with MRI and PET. The Canadian Consortium on Neurodegeneration in Aging (CCNA) Imaging Workgroup aimed to synthesize evidence and provide recommendations on implementing imaging protocols for AD DMTs in Canada.

The workgroup employed a Delphi process to develop these recommendations. Experts from radiology, neurology, biomedical engineering, nuclear medicine, MRI and medical physics were recruited. Surveys and meetings were conducted to achieve consensus on key issues, including protocol standardization, scanner strength, monitoring protocols based on risk profiles and optimal protocol lengths. Draft recommendations were refined through multiple iterations and expert discussions.

The recommendations emphasize standardized acquisition imaging protocols across manufacturers and scanner strengths to ensure consistency and reliability of clinical treatment decisions, tailored monitoring protocols based on DMTs’ safety and efficacy profiles, consistent monitoring regardless of perceived treatment efficacy and MRI screening on 1.5T or 3T scanners with adapted protocols. An optimal protocol length of 20–30 minutes was deemed feasible; specific sequences are suggested.

The guidelines aim to enhance imaging data quality and consistency, facilitating better clinical decision-making and improving patient outcomes. Further research is needed to refine these protocols and address evolving challenges with new DMTs. It is recognized that administrative, financial and logistical capacity to deliver additional MRI and positron emission tomography scans require careful planning.