Esketamine Nasal Spray Research Articles

Effect of Esketamine Nasal Spray on Cognition in Patients with Treatment-Resistant Depression: Results from Four Phase-3 Studies.

While esketamine is effective in treatment-resistant depression (TRD), detailed information about the effect of esketamine on cognition is relatively scarce. This analysis assessed the effect of short-term (three double-blind [DB] studies; DB1, DB2, and DB4) or long-term maintenance treatment (DB3) with esketamine nasal spray (ESK) compared to an active-comparator+placebo (PBO), on cognition in patients with TRD. Patients (DB1/DB2/DB3: [18-64years, n=747]; DB4: [≥65years, n=137]) with TRD received ESK (DB1/DB2/DB3:56/84mg; DB4:28/56/84mg) or PBO+newly initiated oral antidepressant (OAD) as per treatment schedules. Cognitive assessments- Cogstate battery and Hopkins Verbal Learning Test-Revised, were administered at baseline, Day-28/early withdrawal, and follow-up visits in DB1/DB2/DB4 and at 12-week intervals in DB3 maintenance phase. Descriptive statistics were used to analyze ESK effects on cognition with effect sizes and 95% confidence intervals (CIs) used to express the nature/magnitude of treatment effects relative to active-comparator+PBO. Correlation between depression severity (MADRS scores) and cognition was assessed at baseline and endpoint(s). At baseline, mild-to-moderate impairment in psychomotor function, attention, and memory (working/episodic) were evident. For each DB1/DB2/DB4, group mean performance in z-scores for ESK+OAD and OAD+PBO groups on all cognitive tests remained similar/slightly improved from, baseline at endpoint (Day-28) and follow-up assessments. Similarly, in DB3(limited to participants ≥65years), both groups generally showed improvement in cognitive performance at endpoint(s). Correlations between MADRS scores and performance on the cognitive test battery were small at baseline and endpoint(s). This analysis did not identify evidence of negative effects on cognition following short-term or long-term maintenance treatment with ESK+OAD in patients with TRD.

Estimating the benefit of esketamine nasal spray versus real-world treatment on patient-reported functional remission: results from the ICEBERG study.

Treatment resistant depression (TRD) affects approximately 10-30% of patients with major depressive disorder, and most patients with TRD do not respond to real-world treatments (RWT). Treatment with esketamine nasal spray (NS) plus a selective serotonin or serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) has significant long-term clinical benefit over RWT in patients with TRD. However, the impact on patient-reported function remains to be determined. The ICEBERG analysis was an indirect treatment comparison performed using data from two studies of patients with TRD: SUSTAIN-2 (esketamine NS; NCT02497287) and the European Observational TRD Cohort (EOTC; RWT; NCT03373253; clinicaltrials.gov). Here, patient-reported functional remission, assessed using the Sheehan Disability Scale (SDS), was defined as SDS ≤6 at Month 6. Analyses were conducted using propensity score re-weighting and multivariable models based on 18 covariates. At Month 6, the probability of functional remission in esketamine NS-treated patients from SUSTAIN-2 (n=512) was 25.6% (95% confidence interval [CI] 21.8-29.4), while the adjusted probability for RWT patients from the EOTC (n=184) was 11.5% (95% CI 6.9-16.1; relative risk: 2.226 [95% CI 1.451-3.416]; p=0.0003). In the total combined population (N=696), patients who did not achieve clinical response or remission had a low probability of achieving functional remission (5.84% and 8.76%, respectively). However, for patients who did achieve clinical response or remission, the probability of achieving functional remission was greater (43.38% and 54.15%, respectively), although many still did not achieve this status. For patients with TRD, esketamine NS had a significant functional benefit versus RWT after 6 months of treatment. Irrespective of treatment, achievement of clinical response or remission was insufficient to attain functional remission. Nevertheless, clinical remission increased the likelihood of achieving functional remission, further supporting an important role for clinical remission in for the path towards functional recovery.

Challenges for esketamine nasal spray in China: use and management.

Challenges for esketamine nasal spray in China: use and management.

Adis summary of research: Efficacy and safety of esketamine nasal spray in patients with treatment-resistant depression who completed a second induction period: analysis of the ongoing SUSTAIN-3 study

Adis summary of research: Efficacy and safety of esketamine nasal spray in patients with treatment-resistant depression who completed a second induction period: analysis of the ongoing SUSTAIN-3 study

A real-world pharmacovigilance study of esketamine nasal spray.

Mining and updating the post-marketing safety signals of esketamine nasal spray for better identification of adverse drug event (ADE) signals and medication monitoring during clinical use to ensure patient medication safety. Downloading data from the US Food and Drug Administration Adverse Event Reporting System from Q1 2019 to Q2 2023, the reporting odds ratio, proportional reporting ratio, Multi-item Gamma Poisson Shrinker, and Bayesian Confidence Propagation Neural Network methods of the disproportionality method were used to mine and analyze ADEs, and finally to screen for signals of ADEs with esketamine nasal spray as the primary suspected drug. The Preferred Terminology of the Medical Dictionary of Regulatory Activities (version 26.0) was used to standardize the description of ADEs and to attribute ADEs to the System Organ Classification. A total of 5132 ADEs reports of esketamine nasal spray as the primary suspected drug were obtained from the Food and Drug Administration Adverse Event Reporting System. The most frequently observed ADEs are dissociation, sedation, and hypertension, while some new rare signals have been detected, such as interstitial cystitis, substance abuse, and drug diversion. The present study identified significant new ADEs signals for esketamine nasal spray, which may provide a source for healthcare professionals to assess patients' symptoms and risk identification.

Exploring vortioxetine combination with intranasal esketamine: A feasible alternative to SSRI/SNRI? - Insights from the REAL-ESK study

BackgroundTreatment-Resistant Depression (TRD) affects almost 30 % of patients with Major Depressive Disorder (MDD). Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD in combination with a Serotonin Specific Reuptake Inhibitor/SSRI or a Serotonin-Norepinephrine Reuptake Inhibitor/SNRI. There is a lack of studies investigating the effectiveness and safety of ESK-NS in combination with other oral antidepressants. AimTo assess the efficacy of Vortioxetine plus ESK-NS in mitigating depressive symptoms and emotional blunting, as well as its tolerability in TRD subjects, compared to the standard-of-care of SSRI/SNRI plus ESK-NS. MethodsWe conducted a post-hoc analysis of the REAL-ESK study. The study included twenty TRD patients, ten subjects taking Vortioxetine as the main oral antidepressant with ESK-NS, and ten subjects taking SSRI or SNRI with ESK-NS. Psychometric assessments (Montgomery-Åsberg Depression Rating Scale/MADRS, Brief Psychiatric Rating Scale/BPRS) were conducted at baseline(T0), one month(T1), and three months after the treatment initiation(T2). ResultsThe combination of Vortioxetine and ESK-NS was as effective as the standard-of-care in reducing depressive symptoms, with a higher effect size in reducing emotional blunting at T2. The safety and tolerability profile of the Vortioxetine+ESK-NS combination appeared to be better, with a lower rate of treatment-emergent adverse events. ConclusionThe combination of Vortioxetine and ESK-NS may be a valuable alternative to the standard-of-care SSRI/SNRI plus ESK-NS in TRD patients, particularly regarding the reduction of emotional blunting and potentially a better safety and tolerability profile. Further randomized controlled trials with larger sample sizes and prospective designs are needed to confirm these findings.

Real-world demographic and clinical profiles of patients with treatment-resistant depression initiated on esketamine nasal spray

Objective ESKALE is a French, multicentre, observational study of adults with treatment-resistant depression (TRD) treated with esketamine. This interim analysis describes baseline demographic and clinical characteristic evolution in patients included and treated from early access program to post-marketing launch. Methods Data were collected from medical records and included patient characteristics, disease history at esketamine initiation, use of neurostimulation, the patient’s care pathway, and the number of antidepressant treatment lines prescribed prior to esketamine initiation. Descriptive statistics were used for each cohort: the early access program ‘Temporary Authorisation for Use’ (ATU), post-ATU, and post-launch cohorts. Results The overall ESKALE cohort (N = 160 included; n = 157 treated with esketamine; average age 49.0 years; 66.2% female) demonstrated moderate-to-severe depression according to clinical assessment and a mean Montgomery-Åsberg Depression Rating Scale score of 32.6 (8.0); however, severity, subtype, and comorbidities were heterogeneous across the cohorts. Earlier use of esketamine and prior to alternative treatments occurred during the later cohorts. Conclusion These findings demonstrated a high burden of TRD in these patients and that esketamine is used in TRD treatment regardless of their disease severity, subtype, or existing comorbidities. These results also suggest that esketamine is potentially a clinically useful alternative treatment, particularly with healthcare professionals gaining greater familiarity with and easier access to esketamine.

A Multi-Center, Open-Label, Single-Arm Study to Investigate the Early Effectiveness of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression Using a Mobile Self-Monitoring Application.

This study assesses the early effectiveness of esketamine nasal spray (ESK) in adults with treatment-resistant depression (TRD) 1 day after the first administration, as monitored through self-assessment via the mobile application, Esketamine Continuing Assessment for Relapse Prevention (EsCARe). In this multi-center, open-label, single-arm study, adults aged 18-65 years diagnosed with TRD after failing at least two antidepressant therapies were enrolled from five tertiary hospitals in South Korea. During the induction period, participants self-administered ESK twice weekly and used the EsCARe app daily to record mood, sleep, and somatic symptoms. Key clinical assessments, the Patient Health Questionnaire-9 (PHQ-9), the Hamilton Depression Rating Scale (HAMD), and the Generalized Anxiety Disorder Scale (GAD-7), were measured at baseline and at weeks 2 and 4. The reliability and validity of EsCARe was assessed. The treatment results indicated significant improvements in depressive and anxiety symptoms, with notable reductions in the PHQ-9 and the GAD-7 by week 2, and the HAMD by week 4. The EsCARe app reliably and validly monitored depressive symptoms and demonstrated a significant reduction in depressive symptoms 1 day after the first administration of ESK. Using ESK, complemented by mobile self-monitoring, effectively reduces the symptoms of TRD early in the treatment course. Integrating mobile health technology into the therapeutic regimen highlights a significant advancement in managing TRD, offering patients and clinicians immediate feedback on treatment efficacy.

The Resistant Depression Response to Esketamine Assessing Metabolomics (ReDREAM) Project-Untargeted Metabolomics to Identify Biomarkers of Treatment Response to Intranasal Esketamine in Individuals with Treatment-Resistant Depression: A Study Protocol.

Treatment-resistant depression (TRD) affects around 20-30% of people with major depressive disorder. In 2019, esketamine nasal spray was approved for TRD by both the US Food and Drug Administration and the European Medicines Agency. While its clinical efficacy and safety are proven, the mechanisms underlying its antidepressant effect remain unclear. The use of metabolomics may allow understanding the metabolic effects of esketamine and predicting biological features associated with clinical response in TRD. Nonetheless, there is a lack of studies exploring the predictive value of metabolomics. The Resistant Depression Response to Esketamine Assessing Metabolomics (ReDREAM) project aims at identifying metabolic biosignatures that may represent novel correlates of response to esketamine treatment. This is the protocol of an observational, prospective study. We plan to select 60 people with TRD from 3 clinical sites in Italy. The participants will be administered with esketamine nasal spray, following standard clinical practice, twice a week for 4 weeks ("induction phase"), then once a week for 4 additional weeks ("maintenance phase"). We will test the correlations between baseline metabolic profile and depressive symptom improvement at study endpoints (weeks 4 and 8) and we will explore the likelihood of different metabolic phenotypes between responders and non-responders. An involvement of energy metabolism, amino acid metabolism, urea cycle, and nitric oxide synthesis in response to treatment with esketamine nasal spray is hypothesized. Unbiased data from untargeted metabolomics associated with clinical changes after esketamine treatment may contribute to define new paradigms for precision psychiatry-oriented, personalized care of TRD.

Understanding profiles of patients with treatment-resistant depression by stringency of health plan prior authorization criteria for approval of esketamine nasal spray

Objectives In the United States (US), prescription drug coverage is subject to prior authorization (PA) criteria, which may vary between health plans and may exceed drug label requirements. This study aimed to characterize profiles and treatment history of patients with treatment-resistant depression (TRD) who initiated esketamine nasal spray, by stringency of their health plans’ PA criteria relative to the esketamine label. Methods Adults with evidence of TRD (≥2 antidepressant courses of adequate dose and duration) prior to initiating esketamine were identified using US insurance claims data (03/2016–02/2022). Based on health plan PA criteria for esketamine obtained from Managed Markets Insight & Technology data (05/2020–02/2022), patients were grouped into stringent (PA criteria exceeds label) and non-stringent (PA criteria less stringent or equal to label) cohorts. Patient treatment history before esketamine initiation was compared using Wilcoxon rank sum and Fisher’s exact tests. Results The stringent cohort included 168 patients (mean age: 45 years, 63% female) and the non-stringent cohort included 400 patients (mean age: 45 years, 70% female). During the ongoing major depressive episode before esketamine initiation, the stringent versus non-stringent cohort completed 3.9 versus 3.8 antidepressant treatment courses, on average (p = 0.217); 94.6% versus 96.8% used augmentation therapy (p = 0.240), including 59.3% versus 58.1% with an antipsychotic (p = 0.844), respectively. Conclusions Regardless of health plan stringency, on average, patients exceeded US label-mandated number of antidepressant trials before esketamine initiation, which questions the need for health insurance plans PA criteria above label.

Overcoming treatment-resistant depression with machine-learning based tools: a study protocol combining EEG and clinical data to personalize glutamatergic and brain stimulation interventions (SelecTool Project).

Treatment-Resistant Depression (TRD) poses a substantial health and economic challenge, persisting as a major concern despite decades of extensive research into novel treatment modalities. The considerable heterogeneity in TRD's clinical manifestations and neurobiological bases has complicated efforts toward effective interventions. Recognizing the need for precise biomarkers to guide treatment choices in TRD, herein we introduce the SelecTool Project. This initiative focuses on developing (WorkPlane 1/WP1) and conducting preliminary validation (WorkPlane 2/WP2) of a computational tool (SelecTool) that integrates clinical data, neurophysiological (EEG) and peripheral (blood sample) biomarkers through a machine-learning framework designed to optimize TRD treatment protocols. The SelecTool project aims to enhance clinical decision-making by enabling the selection of personalized interventions. It leverages multi-modal data analysis to navigate treatment choices towards two validated therapeutic options for TRD: esketamine nasal spray (ESK-NS) and accelerated repetitive Transcranial Magnetic Stimulation (arTMS). In WP1, 100 subjects with TRD will be randomized to receive either ESK-NS or arTMS, with comprehensive evaluations encompassing neurophysiological (EEG), clinical (psychometric scales), and peripheral (blood samples) assessments both at baseline (T0) and one month post-treatment initiation (T1). WP2 will utilize the data collected in WP1 to train the SelecTool algorithm, followed by its application in a second, out-of-sample cohort of 20 TRD subjects, assigning treatments based on the tool's recommendations. Ultimately, this research seeks to revolutionize the treatment of TRD by employing advanced machine learning strategies and thorough data analysis, aimed at unraveling the complex neurobiological landscape of depression. This effort is expected to provide pivotal insights that will promote the development of more effective and individually tailored treatment strategies, thus addressing a significant void in current TRD management and potentially reducing its profound societal and economic burdens.

Safety and tolerability of esketamine nasal spray versus quetiapine extended release in patients with treatment resistant depression

In ESCAPE-TRD (NCT04338321), esketamine nasal spray (NS) significantly increased the probability of remission at Week 8, and of being relapse-free through Week 32 after remission at Week 8, versus quetiapine extended release (XR) in patients with treatment resistant depression (TRD). Here, we explore the time course, burden and consequences of treatment emergent adverse events (TEAEs) in the phase IIIb ESCAPE‑TRD trial. Patients with TRD were randomised 1:1 to esketamine NS or quetiapine XR, dosed per label alongside an ongoing selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor. In this secondary publication, safety analyses (comprising patients who received ≥1 dose of study treatment) included incidence, severity and durations (Kaplan‑Meier method) of TEAEs, and subsequent dispositional changes. P values were not adjusted for multiple testing. 336 patients were randomised to esketamine NS and 340 to quetiapine XR; 334 and 336 received ≥1 dose of study treatment, respectively. TEAEs were significantly more common with esketamine NS than quetiapine XR (91.9 % versus 78.0 %; p < 0.001), but were typically mild/moderate and transient in nature: a greater proportion resolved on the same-day (92.0 % versus 12.1 %) and lead to treatment discontinuation in significantly fewer patients (4.2 % versus 11.0 %, respectively; p < 0.001). The proportion of days spent with TEAEs was significantly lower with esketamine NS than quetiapine XR (median: 11.9 % versus 21.3 %; p < 0.001). Although more frequent with esketamine NS, TEAEs were typically transient and mild, with discontinuation less likely versus quetiapine XR. Data were consistent with established safety profiles, with no new safety signals identified. Alongside greater efficacy, the demonstrably more favourable tolerability profile of esketamine NS versus quetiapine XR further supports its use for TRD.

SA29 Motivations and Barriers for Psychiatric Practice Adoption of Esketamine Nasal Spray for Treatment-Resistant Depression in the United States

SA29 Motivations and Barriers for Psychiatric Practice Adoption of Esketamine Nasal Spray for Treatment-Resistant Depression in the United States

A real-world study examining the impact of esketamine nasal spray in people living with major depressive disorder in Australia and New Zealand

IntroductionEsketamine has been approved in Australia and New Zealand as a third-line antidepressant treatment for treatment resistant depression. This study describes changes in quality of life, depressive symptoms and productivity in participants treated with esketamine in real-world settings. MethodsParticipants were recruited from an esketamine early access program and had not responded to two or more different antidepressants and not received neurostimulation for their current depressive episode. Participants received esketamine for 16 weeks or longer. Data collected included Assessment of Quality-of-Life scale (AQoL-8D), Hamilton Depression Rating Scale (HAM-D) and Work Productivity Activity Index (WPAI). ResultsParticipants (n = 105) had a mean age of 38.7 years (standard deviation (SD) = 14.6) and were predominantly female (59.0%). The mean duration of major depressive disorder was 7.2 years (SD = 4.2) and almost half of participants had been treated with 3–5 prior therapies. After 16-weeks on esketamine, participants showed improvement of greater than 10% across all dimensions of AQoL-8D, HAM-D scores decreased 8.0 points, and activity impairment decreased 20.4% as measured by WPAI. LimitationsThis was a non-randomized and unblinded study and may have selection and reporting bias. The population was not necessarily representative of the broader Australian and New Zealand population. It is not possible to determine if the results will be sustained or changed if participants received treatment for longer. ConclusionsEsketamine early access program participants, who were a real-world cohort with extensive prior treatment, showed clinically significant improvements in quality of life, depression severity and productivity after 16-weeks on treatment.

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

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. 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. 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 73.2days in the main cohort and 78.8days in the subgroup (per label, 28days). 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. 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.

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

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

Ketamine and its enantiomers for depression: a bibliometric analysis from 2000 to 2023.

Ketamine has demonstrated rapid and sustained antidepressant effects, marking its emergence as an innovative treatment of depression. Despite the growing number of preclinical and clinical studies exploring the antidepressant effects of ketamine and its enantiomers, a comprehensive bibliometric analysis in this field has yet to be conducted. This study employs bibliometric methods and visualization tools to examine the literature and identify key topics related to the antidepressant effects of ketamine and its enantiomers. We sourced publications on the antidepressant effects of ketamine and its enantiomers from the Web of Science Core Collection (WOSCC) database, covering the period from 2000 to 2023. Tools such as VOSviewer, CiteSpace and the R package "bibliometrix" were utilized for visual analysis. The study included 4,274 publications, with a notable increase in publications peaking in 2022. Co-occurrence analysis highlighted two primary research focal points: the efficacy and safety of ketamine and its enantiomers in treating depression, and the mechanisms behind their antidepressant effects. In conclusion, this analysis revealed a significant increase in research on the antidepressant effects of ketamine and its enantiomers over the past two decades, leading to the approval of esketamine nasal spray for treatment-resistant depression. The rapid antidepressant effects of ketamine have spurred further studies into its mechanisms of action and the search for new antidepressants with fewer side effects.

Perspectives in treatment-resistant depression: esketamine and electroconvulsive therapy.

Modern electroconvulsive therapy (ECT) and the approval of nasal esketamine for clinical use have significantly improved the approach to treatment-resistant depression (TRD), which is defined as non-response to at least two different courses of antidepressants with verified adherence to treatment, adequate dosage, and duration of treatment. The goal of this literature review is to present the newest evidence regarding efficacy and safety. Furthermore, we aim to provide an overview of future perspectives in this field of research, for example, regarding structural and molecular effects. Both treatment methods will be critically evaluated for their individual advantages, disadvantages, and response rates. Firstly, we will discuss the well-established method of ECT and its different treatment modalities. Secondly, we will discuss the properties of ketamine, the discovery of its antidepressive effects and the route to clinical approval of the esketamine nasal spray. We will comment on research settings which have evaluated intravenous ketamine against ECT. The decision-making process between esketamine nasal spray or ECT should include the assessment of contraindications, age, severity of disease, presence of psychotic symptoms, patient preference and treatment accessibility. We conclude that both treatment options are highly effective in TRD. If both are indicated, pragmatically esketamine will be chosen before ECT; however, ECT studies in ketamine non-responders are missing.

Weight changes in esketamine nasal spray and quetiapine extended-release treated patients with treatment resistant depression: Results from ESCAPE-TRD study

IntroductionIn ESCAPE-TRD, esketamine nasal spray (ESK-NS) significantly increased the probability of remission at Week (Wk)8 and being relapse‑free through Wk32 after remission at Wk8 versus (vs) quetiapine extended-release (QTP-XR), in patients (pts) with treatment resistant depression (TRD). Safety data were consistent with established profiles of each treatment, with no new safety signals identified (Reif et al. DGPPN 2022; P-01-04).ObjectivesTo explore weight changes and their impact on treatment discontinuation in ESCAPE-TRD.MethodsESCAPE‑TRD (NCT04338321) was a randomised, open-label, rater-blinded, phase IIIb trial comparing efficacy and safety of ESK-NS vs QTP-XR in pts with TRD. Safety analyses were conducted on pts who received ≥1 dose of study treatment. Treatment-emergent adverse events (TEAEs) were defined as occurring at or after the first dose of study treatment and within 14 days/30 days (non-serious/serious) of the last dose. A ≥7% increase/decrease in weight from screening was considered for evaluation as a TEAE. Weights were measured and are reported as observed, with no missing data imputation.Results336 and 340 pts were randomised to ESK-NS and QTP-XR; 334 and 336 were included in the safety population. Over the 32-week study, a TEAE of weight increase was reported in fewer pts treated with ESK-NS than QTP-XR (9 [2.7%] vs 42 [12.5%]), leading to treatment discontinuation in 0 vs 6 (1.8%) pts, respectively. Incidences of weight increase TEAEs were balanced across pts categorised as normal, overweight or obsese by baseline body mass index (BMI; Figure). A weight decrease TEAE was reported in 7 pts (2.1%) in the ESK-NS arm vs 0 pts in the QTP-XR arm. Mean (standard deviation [SD]) weight at baseline was 76.4 (16.2) kg (ESK-NS; n=334) vs 79.1 (16.9) kg (QTP-XR; n=336). At Wk32, mean weight was maintained (76.5 [16.3] kg) in ESK-NS treated pts (n=249; mean [SD] change from baseline: 0.1 [4.0] kg) and increased (80.7 [15.6] kg) in QTP-XR treated pts (n=203; mean [SD] change from baseline: 2.5 [5.1] kg).Image:ConclusionsIncrease in weight was uncommon with ESK-NS; weight increases were more common with QTP-XR and resulted in more treatment discontinuations. Weight increase was independent from baseline BMI.AcknowledgementsWe thank the patients who participated. Funding: Janssen, medical writing: Costello Medical, UKDisclosure of InterestNone Declared

How adults with treatment resistant depression experience their first esketamine nasal spray treatment? Preliminary results from a French qualitative study

IntroductionSpravato® (esketamine nasal spray- ENS) is a new adjunctive drug for Treatment Resistant Depression (TRD), i.e. patients with major depressive disorder that failed to adequately respond despite the use of two different antidepressants. In France, a real world non-interventional post-commercialization cohort study is being conducted aiming to describe the conditions of use of the esketamine, and to observe the outcomes.ObjectivesTo in-depth explore the lived experience of first administered ENS treatment among adults with TRD, we are conducting an ancillary qualitative study.MethodsThis qualitative study uses the IPSE approach (Sibeoni et al. BMC Medical Research Methodology 20.1(2020):1-21) and has been conducted in four French psychiatric departments. Design was based on the recruitment of patients through the Cohort study, all interviewed twice, the first time 3 to 5 weeks after the first administration of ENS, and the second time around 6 months after, whether treatment has been continued or not. Data analysis follows the IPSE analytic procedure and is conducted in two stages: three individual researchers carry out independent work and the group collectively pools data. These preliminary results are based on the sole analysis of the first interviews conducted from July 2022 to July 2023.ResultsEighteen participants with moderate to severe TRD, including 13 women, were interviewed and two axes of experience have been produced: (1) the overwhelming experiences of the treatment, perceived differently depending on patients, as a dissociative experience, both inside – described as a trip- and outside of them; (2) A discordant treatment experience with both solitude and relational support from medical team.ConclusionsThese results highlight the need to better prepare the patients for the initiation of the treatment and to take into consideration the settings in which the treatment is administered, as well as the importance of the support received from the nursing staff.Disclosure of InterestE. Manolios Grant / Research support from: have recieved financial support to conduct the study, J. Mathé Grant / Research support from: have recieved financial support to conduct the study, J. Sibeoni Grant / Research support from: have recieved financial support to conduct the study, M. Rotharmel Consultant of: Janssen, B. Astruc Consultant of: Janssen, B. Falissard Consultant of: Janssen, L. Mekaoui Consultant of: Janssen, A. Laurin Consultant of: Janssen, E. Gaudre-Wattinne Employee of: Janssen Cilag, J. Dupin Employee of: Janssen Cilag, A. Revah-Levy Grant / Research support from: have recieved financial support to conduct the study