Esketamine Nasal Spray Research Articles

Effects of esketamine on patient-reported outcomes in major depressive disorder with active suicidal ideation and intent: a pooled analysis of two randomized phase 3 trials (ASPIRE I and ASPIRE II)

PurposeTo assess the effect of esketamine nasal spray on patient-reported outcomes (PROs) in patients with major depressive disorder having active suicidal ideation with intent (MDSI).MethodsPatient-level data from two phase 3 studies (ASPIRE I; ASPIRE II) of esketamine + standard of care (SOC) in patients (aged 18–64 years) with MDSI, were pooled. PROs were evaluated from baseline through end of the double-blind treatment phase (day 25). Outcome assessments included: Beck Hopelessness Scale (BHS), Quality of Life (QoL) in Depression Scale (QLDS), European QoL Group-5-Dimension-5-Level (EQ-5D-5L), and 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9). Changes in BHS and QLDS scores (baseline to day 25) were analyzed using a mixed-effects model for repeated measures (MMRM).ResultsPooled data for esketamine + SOC (n = 226; mean age: 40.5 years, 59.3% females) and placebo + SOC (n = 225; mean age: 39.6 years, 62.2% females) were analyzed. Mean ± SD change from baseline to day 25, esketamine + SOC vs placebo + SOC (least-square mean difference [95% CI] based on MMRM): BHS total score, − 7.4 ± 6.7 vs − 6.8 ± 6.5 [− 1.0 (− 2.23, 0.21)]; QLDS score, − 14.4 ± 11.5 vs − 12.2 ± 10.8 [− 3.1 (− 5.21, − 1.02)]. Relative risk (95% CI) of reporting perceived problems (slight to extreme) in EQ-5D-5L dimensions (day 25) in esketamine + SOC vs placebo + SOC: mobility [0.78 (0.50, 1.20)], self-care [0.83 (0.55, 1.27)], usual activities [0.87 (0.72, 1.05)], pain/discomfort [0.85 (0.69, 1.04)], and anxiety/depression [0.90 (0.80, 1.00)]. Mean ± SD changes from baseline in esketamine + SOC vs placebo + SOC for health status index: 0.23 ± 0.21 vs 0.19 ± 0.22; and for EQ-Visual Analogue Scale: 24.0 ± 27.2 vs 19.3 ± 24.4. At day 25, mean ± SD in domains of TSQM-9 scores in esketamine + SOC vs placebo + SOC were: effectiveness, 67.2 ± 25.3 vs 56.2 ± 26.8; global satisfaction, 69.9 ± 25.2 vs 56.3 ± 27.8; and convenience, 74.0 ± 19.4 vs 75.4 ± 18.7.ConclusionThese PRO data support the patient perspective of the effect associated with esketamine + SOC in improving health-related QoL in patients with MDSI.Trial registration: ClinicalTrials.gov Identifier: ASPIRE I, NCT03039192 (Registration date: February 1, 2017); ASPIRE II, NCT03097133 (Registration date: March 31, 2017).

Investigating the Effectiveness and Tolerability of Intranasal Esketamine Among Older Adults With Treatment-Resistant Depression (TRD): A Post-hoc Analysis from the REAL-ESK Study Group

IntroductionTreatment-resistant depression (TRD) is a serious and debilitating psychiatric disorder that frequently affects older patients. Esketamine nasal spray (ESK-NS) has recently been approved as a treatment for TRD, with multiple studies establishing its efficacy and tolerability. However, the real-world effectiveness, tolerability, and safety of this treatment in older adults is still unclear. ObjectivesTo evaluate the efficacy and tolerability of ESK-NS in older subjects with TRD. MethodsThis is a post-hoc analysis of the REAL-ESK study, a multicenter, retrospective, observational study. Participants here selected were 65 years or older at baseline. The Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A) were used to assess depressive and anxiety symptoms, respectively. Data were collected at three-time points: baseline, 1 month after the start of treatment (T1), and 3 months after treatment (T2). ResultsThe sample included older adults with TRD (n = 30). MADRS and HAM-A values decreased significantly at T1 (T0 versus T1: pholm <0.001, Cohen's d = 0.840) and T2 follow-ups (T0 versus T2: pholm <0.001, Cohen's d = 1.419). At T2, 53.3% of subjects were responders (MADRS score reduced ≥50%), while 33.33% were in remission (MADRS<10). ESK-NS-related adverse effects were in order of frequency dizziness (50%), followed by dissociation (33.3%), sedation (30%), and hypertension (13.33%). Six out of 30 participants (20%) discontinued treatment. ConclusionsOur findings provide preliminary evidence of ESK-NS effectiveness in older adults with TRD, a highly debilitating depressive presentation. Furthermore, we observe high levels of treatment-emergent adverse events, which, in the majority of instances, did not require treatment suspension.

Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study

Patients with treatment-resistant depression (TRD) have higher rates of relapse and pronounced decreases in daily functioning and health-related quality of life compared to patients with major depressive disorder who are not treatment-resistant, underscoring the need for treatment choices with sustained efficacy and long-term tolerability. Adults with TRD who participated in ≥1 of 6 phase 3 “parent” studies could continue esketamine treatment, combined with an oral antidepressant, by enrolling in phase 3, open-label, long-term extension study, SUSTAIN-3. Based on their status at parent-study end, eligible participants entered a 4-week induction phase followed by an optimization/maintenance phase, or directly entered the optimization/maintenance phase of SUSTAIN-3. Intranasal esketamine dosing was flexible, twice-weekly during induction and individualized to depression severity during optimization/maintenance. At the interim data cutoff (01 December 2020), 1148 participants were enrolled, 458 at induction and 690 at optimization/maintenance. Mean (median) cumulative duration of maintenance esketamine treatment was 31.5 (37.7) months (totaling 2769 cumulative patient-years). Common treatment-emergent adverse events (≥20%) were headache, dizziness, nausea, dissociation, somnolence, and nasopharyngitis. Mean Montgomery–Åsberg Depression Rating Scale (MADRS) total score decreased during induction, and this reduction persisted during optimization/maintenance (mean [SD] change from the baseline to the endpoint of each phase: induction −12.8 [9.73]; optimization/maintenance +1.1 [9.93]), with 35.6% and 46.1% of participants in remission (MADRS total score ≤12) at induction and optimization/maintenance endpoints, respectively. Improvement in depression ratings generally persisted among participants who remained in maintenance treatment, and no new safety signal was identified during long-term treatment (up to 4.5 years) using intermittent-dosed esketamine in conjunction with daily antidepressant.

Assessment of health-related quality of life and health status in patients with treatment-resistant depression treated with esketamine nasal spray plus an oral antidepressant

BackgroundPatients with treatment-resistant depression (TRD) report significant deficits in physical and mental health, as well as severely impaired health-related quality of life (HRQoL) and functioning. Esketamine effectively enhances the daily functioning in these patients while also improving their depressive symptoms. This study assessed HRQoL and health status of patients with TRD, who were treated with esketamine nasal spray and an oral antidepressant (ESK + AD) vs. placebo nasal spray and an AD (AD + PBO).MethodsData from TRANSFORM-2, a phase 3, randomized, double-blind, short-term flexibly dosed study, were analyzed. Patients (aged 18–64 years) with TRD were included. The outcome assessments included the European Quality of Life Group, Five Dimension, Five Level (EQ-5D-5L), EQ-Visual Analogue Scale (EQ-VAS), and Sheehan Disability Scale (SDS). The health status index (HSI) was calculated using EQ-5D-5L scores.ResultsThe full analysis set included 223 patients (ESK + AD: 114; AD + PBO: 109; mean [SD] age: 45.7 [11.89]). At Day 28, a lower percentage of patients reported impairment in the ESK + AD vs. AD + PBO group in all five EQ-5D-5L dimensions: mobility (10.6% vs. 25.0%), self-care (13.5% vs. 32.0%), usual activities (51.9% vs. 72.0%), pain/discomfort (35.6% vs. 54.0%), and anxiety/depression (69.2% vs. 78.0%). The mean (SD) change from baseline in HSI at Day 28 was 0.310 (0.219) for ESK + AD and 0.235 (0.252) for AD + PBO, with a higher score reflecting better levels of health. The mean (SD) change from baseline in EQ-VAS score at Day 28 was greater in ESK + AD (31.1 [25.67]) vs. AD + PBO (22.1 [26.43]). The mean (SD) change in the SDS total score from baseline to Day 28 also favored ESK + AD (-13.6 [8.31]) vs. AD + PBO (-9.4 [8.43]).ConclusionsGreater improvements in HRQoL and health status were observed among patients with TRD treated with ESK + AD vs. AD + PBO.Trial registrationClinicalTrials.gov Identifier: NCT02418585.

Esketamine in treatment-resistant depression patients comorbid with substance-use disorder: A viewpoint on its safety and effectiveness in a subsample of patients from the REAL-ESK study

Esketamine, the S-enantiomer of ketamine, has recently emerged as a therapy for treatment-resistant depression (TRD), showing both rapid antidepressant action and good efficacy and high safety. It is also indicated for the acute short-term treatment of psychiatric emergency due to major depressive disorder (MDD) and for depressive symptoms in adults with MDD with acute suicidal thoughts/behavior. We here provide preliminary insights on esketamine nasal spray (ESK-NS) effectiveness and safety among patients with a substance use disorder (SUD) within the sample of patients with TRD collected for the observational, retrospective, multicentre REAL-ESK study. Twenty-six subjects were retrospectively selected according to the presence of a SUD in comorbidity. Subjects enrolled completed the three different follow-up phases (T0/baseline, T1/after one month, and T2/after three months) and there were no dropouts. A decrease in Montgomery-Asberg depression rating scale (MADRS) scores was recorded, thus highlighting the antidepressant efficacy of ESK-NS (MADRS decreased from T0 to T1, t = 6.533, df=23, p<0.001, and from T1 to T2, t = 2.029, df=20, p = 0.056). Considering tolerability and safety issues, one or more side effects were reported by 19/26 subjects (73%) after treatment administration. All reported side effects were time-dependent and did not cause significant sequelae; among them, dissociative symptoms (38%) and sedation (26%) were the most frequently reported. Finally, no cases of abuse or misuse of ESK-NS were reported. Despite study limitations related to the inherent nature of the study, a limited number of patients, and a short follow-up period, ESK-NS showed to be effective and safe in patients diagnosed with TRD comorbid with a SUD.

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

AimsTo 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).MethodsAdults 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.ResultsAmong 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.LimitationsThis 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.ConclusionsNearly 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.

Unsubstantiated use of Selective serotonin reuptake inhibitors as an alternative for the treatment of depression

Unsubstantiated use of Selective serotonin reuptake inhibitors as an alternative for the treatment of depression

233. Transcriptional Profiling of Peripheral Blood in Depressive Patients Treated With Esketamine Nasal Spray

233. Transcriptional Profiling of Peripheral Blood in Depressive Patients Treated With Esketamine Nasal Spray

Predictors of response and remission in patients with treatment-resistant depression: A post hoc pooled analysis of two acute trials of esketamine nasal spray

This exploratory post hoc analysis of two pooled 4-week, phase 3, double-blind, placebo- and active-controlled studies that compared esketamine nasal spray plus a newly initiated oral antidepressant (ESK+AD; n = 310) with a newly initiated oral AD plus placebo nasal spray (AD+PBO; n = 208) in patients with treatment-resistant depression (TRD) examined baseline patient demographic and psychiatric characteristics as potential predictors of response (≥50% reduction from baseline in Montgomery–Åsberg Depression Rating Scale [MADRS] total score) and remission (MADRS total score ≤12) at day 28. Overall, younger age, any employment, fewer failed ADs in the current depressive episode, and reduction in Clinical Global Impression-Severity (CGI-S) score at day 8 were significant positive predictors of response and remission at day 28. Treatment assignment was an important predictor of both response and remission. Patients treated with ESK+AD had 68% and 55% increased odds of achieving response and remission, respectively, versus those treated with AD+PBO. In the ESK+AD group, attainment of response and remission was more likely in patients who were employed, without significant anxiety at baseline, and who experienced a reduction in CGI-S score at day 8. Identification of predictors of response and remission may facilitate identification of those patients with TRD most likely to benefit from ESK+AD.Trial Registration: ClinicalTrials.gov: NCT02417064 (clinicaltrials.gov/ct2/show/NCT02417064) and NCT02418585 (clinicaltrials.gov/ct2/show/NCT02418585)

Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Plus a Newly Initiated Oral Antidepressant in Adult Patients with Treatment-Resistant Depression: A Randomized, Double-Blind, Multicenter, Active-Controlled Study Conducted in China and USA.

This Phase 3, multicenter study (NCT03434041) was conducted in primarily Chinese patients with treatment-resistant depression (TRD) to support the registration of esketamine nasal spray in China. This randomized, double-blind, active-controlled study was conducted in China and the United States (US) in patients with TRD (single or recurrent episode). Eligible patients were randomized 1:1 to receive intranasal esketamine or matching placebo, each in conjunction with a newly initiated oral antidepressant (AD; duloxetine, escitalopram, sertraline, and venlafaxine extended release) (ie, esketamine plus AD or AD plus placebo). The primary endpoint, change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Day 28, was analyzed using a mixed-effects model for repeated measures. Secondary endpoints including safety were also evaluated. Of 252 randomized patients (China, 224; US, 28), 214 completed the double-blind treatment phase. The difference between treatment groups at Day 28 was not statistically significant (difference in least-square means [95% CI]: -2.0 [-4.64, 0.55]; 2-sided p = 0.123). However, esketamine plus AD demonstrated a clinically meaningful treatment difference compared with AD plus placebo in MADRS total score at 24 hours after first dose for the study overall population and China sub-population (difference in least-square mean [95% CI]: -3.3 [-5.33, -1.33] and -2.6 [-4.64, -0.60], respectively). No new safety signals were observed. Esketamine plus AD was not statistically superior to AD plus placebo in improving depressive symptoms in TRD patients at Day 28. Rapid reduction in depressive symptoms within 24 hours was observed for TRD patients treated with esketamine plus AD in the overall population and China sub-population. Safety was consistent with the established safety profile of esketamine.

Pharmacotherapies for Treatment-Resistant Depression: How Antipsychotics Fit in the Rapidly Evolving Therapeutic Landscape.

One in three adults with major depressive disorder (MDD) do not experience clinically significant improvement after multiple sequential courses of antidepressants and have treatment-resistant depression (TRD). The presence of TRD contributes to the morbidity and excess mortality associated with MDD and has been linked to significantly increased health care expenses. In the absence of a consensus definition of TRD, this report takes a broad approach by considering inadequate response to one or more courses of antidepressants and focuses on atypical antipsychotics that are approved by the U.S. Food and Drug Administration for treatment of depression (aripiprazole, brexpiprazole, cariprazine, extended-release quetiapine, and olanzapine-fluoxetine combination). While multiple acute-phase studies have demonstrated the efficacy of these medications in improving depressive symptoms, clinically meaningful improvement (i.e., remission) remains limited, with significant concerns about side effects (including weight gain, metabolic dysfunction, extrapyramidal symptoms, and tardive dyskinesia), especially with long-term use. With the rapidly evolving landscape of antidepressant treatments over the past few years, which has witnessed approval of rapid-acting antidepressants (e.g., esketamine nasal spray and dextromethorphan-bupropion combination) and several more in the late-stage pipeline (e.g., zuranolone and psilocybin), it remains to be seen whether the use of atypical antipsychotics will go the way of the older and rarely prescribed antidepressants (such as tricyclics and monoamine oxidase inhibitors). Pragmatic clinical trials are needed to compare the effectiveness of atypical antipsychotics with TRD-specific pharmacotherapies and neuromodulation treatments and to identify the optimal sequencing of these varied approaches for patients with MDD. When using atypical antipsychotics, clinicians and patients are encouraged to use a shared decision-making approach by personalizing treatment selection based on anticipated side effects, tolerability, cost, and feasibility.

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.

Early Clinical Experiences of Esketamine Nasal Spray in the UK in Adults with Treatment-Resistant Major Depressive Disorder: Advisory Panel Recommendations.

Treatment-resistant depression (TRD) is associated with profound morbidity for patients, placing a significant burden on those affected, the health service and wider society. Despite this, TRD remains chronically underserved in terms of viable treatment options. To address this gap, an advisory panel of psychiatrists and clinical researchers with experience in managing TRD convened to develop best practice statements on the use of esketamine nasal spray, one of the first TRD treatments to be licensed in 30 years. During a virtual meeting held on 12th November 2020, the advisory panel shared their experiences of using esketamine nasal spray in their clinical practice. The meeting focused on developing and refining recommendations for setting up and running an efficient esketamine nasal spray clinic for patients living with TRD. At the conclusion of the meeting, agreement was reached on all recommendation statements. In setting up an esketamine nasal spray clinic, it is important to consider the logistical requirements involved and put measures in place to ensure it runs as efficiently as possible. Educating patients about the treatment and maintaining their well-being is paramount for preventing discontinuation. Putting in place checklists can be a useful strategy for ensuring treatment appointments run smoothly and safely. Providing additional treatment options for the management of TRD, such as esketamine nasal spray, is likely to be key to improving the long-term outcomes of this underserved patient population.

Cost-Utility Analysis of Esketamine for Patients with Treatment-Resistant Depression in Italy.

Major depressive disorder is considered one of the most frequent diseases in the general population, and treatment-resistant depression (TRD) represents the subset with more significant clinical and social impact. Large, robust phase III studies have shown safety and efficacy of esketamine nasal spray plus SSRI/SNRI antidepressants (ADs) compared with SSRI/SNRI plus placebo nasal spray in patients with TRD. The main aim of this study was to perform a cost-utility analysis comparing esketamine plus ADs with ADs alone in TRD patients, from the societal perspective in Italy. A secondary analysis focused on the National Healthcare Service (NHS) perspective. A Markov multistate model has been developed to estimate quality-adjusted life years and economic outcomes of both treatment strategies over 5years considering the initiation of esketamine in the different treatment lines, from 3 to 5 (3L-5L). The model has been populated with data from literature and real-world evidence. The analysis from the societal perspective considered direct healthcare costs and patients' productivity losses. In addition to the incremental cost-utility ratio (ICUR), the incremental net monetary benefit (INMB) has been calculated as (incremental benefit × WTP) - incremental cost and by applying a willingness-to-pay (WTP) of 50,000€/QALY. Deterministic and probabilistic sensitivity analyses have been performed to assess the robustness of the model results. From the societal perspective, the ICUR ranged between 16,314€ and 22,133€ per QALY according to the different treatment lines, while it was over the threshold of 100,000€/QALY for the NHS perspective. The INMB was positive and ranged from 2259€ to 2744€ across treatment lines in the societal perspective; the INMB begins to occur earlier when moving towards subsequent lines of treatment (3.9years for 3L, 3.6years for 4L and 3.5years for 5L). The analyses showed also that the advantage in terms of INMB is maintained for a wide range of societal preferences expressed by WTP thresholds, and in particular for values above 22,200€, 16,400€ and 17,100€ for 3L, 4L and 5L, respectively. The study showed that esketamine may be a cost-effective opportunity from the societal perspective for the management of patients with treatment-resistant depression. In the future, data collected from observational studies or registries, which can include the collection of productivity losses and also costs sustained by the patients, will be able to provide further evidence in order to improve the reliability of the model results.

ESKALE, french observational study describing treatment strategies and safety of patients with treatment-resistant depression treated with esketamine nasal spray

ESKALE, french observational study describing treatment strategies and safety of patients with treatment-resistant depression treated with esketamine nasal spray

Esketamine nasal spray in treatment-resistant depression: Efficacy and tolerability in a “real-life” setting

Esketamine nasal spray in treatment-resistant depression: Efficacy and tolerability in a “real-life” setting

Long-term safety and maintenance of response with esketamine nasal spray in treatment-resistant depression – final results of the SUSTAIN-3 study

Long-term safety and maintenance of response with esketamine nasal spray in treatment-resistant depression – final results of the SUSTAIN-3 study

Med Check: Alzheimer’s Agitation, Idiopathic Hypersomnia, Depression, and More

Back to table of contents Previous article Next article Med CheckFull AccessMed Check: Alzheimer’s Agitation, Idiopathic Hypersomnia, Depression, and MoreTerri D’ArrigoTerri D’ArrigoSearch for more papers by this authorPublished Online:4 Jan 2023https://doi.org/10.1176/appi.pn.2023.01.1.5AXS-05 May Delay Relapse of Alzheimer’s AgitationAxsome Therapeutics’ investigational combination drug AXS-05 (45 mg dextromethorphan/105 mg bupropion) may delay relapse of agitation associated with Alzheimer’s disease, the company announced in November.In the phase 3 ACCORD trial, 108 patients with Alzheimer’s disease agitation who had already responded to AXS-05 in a previous, open-label trial either continued treatment with the drug or were switched to placebo for up to 26 weeks. Relapse was defined as a worsening of 10 points or more on the Cohen-Mansfield Agitation Inventory (CMAI) from the time the patients were randomized to either continued treatment or to placebo, a CMAI total score greater than when they entered the study, or hospitalization or other institutionalization because of agitation associated with Alzheimer’s disease.Patients who took AXS-05 had a 3.6-fold lower risk of relapse compared with those who took placebo. During the trial, 7.5% of patients who took the drug experienced a relapse of Alzheimer’s disease agitation, compared with 25.9% of those who took placebo. Serdexmethylphenidate Granted Orphan Drug Status for Idiopathic Hypersomnia The Food and Drug Administration (FDA) has granted orphan drug status to serdexmethylphenidate for the treatment of idiopathic hypersomnia, KemPharm Inc. announced in November. Serdexmethylphenidate is KemPharm’s prodrug of d-methylphenidate.The FDA may grant orphan drug status to investigational therapies that address rare medical diseases or conditions. If the drug later receives FDA approval for treating the disease or condition, the FDA may not approve any other applications to market the same drug for the same indication for seven years, except in limited circumstances.KemPharm will soon begin a phase 2 trial of serdexmethylphenidate in patients with idiopathic hypersomniaand a second trial in patients with narcolepsy.Serdexmethylphenidate is also an active ingredient in Corium’s Azstarys (serdexmethylphenidate and dexmethylphenidate), which the FDA approved in March of 2021 for treating symptoms of attention-deficit/hyperactivity disorder in patients aged 6 years and older. Spravato May Be More Effective Than Quetiapine XR for TRDAn open-label phase 3b trial suggests that Spravato (esketamine nasal spray) may have greater efficacy than quetiapine extended release (XR) for treating symptoms of treatment-resistant depression (TRD) in adults, Janssen Pharmaceutical Companies announced in November. Janssen is the manufacturer of Spravato.In the ESCAPE-TRD trial, 676 patients with TRD were randomized to receive either Spravato or quetiapine XR, both in combination with a continuing selective serotonin reuptake inhibitor or serotonin and norepinephrine reuptake inhibitor, for 32 weeks. At the eighth week, 21.7% of the patients who received Spravato experienced remission of their symptoms, compared with 14.1% of those who took quetiapine. At study’s end, symptoms abated in 55% of patients who took Spravato, compared with 37% of those who took quetiapine FDA to Review IPX203 for Parkinson’s DiseaseIn November, Amneal Pharmaceuticals Inc. announced that the FDA has accepted for review the company’s New Drug Application for IPX203 (carbidopa/levodopa extended release) for the treatment of Parkinson’s disease.In the phase 3 RISE-PD trial, 506 patients who were at least 40 years old when they were diagnosed with Parkinson’s disease were randomized to receive either IPX203 or immediate-release carbidopa/levodopa. All patients had motor fluctuations.The primary endpoint was change from baseline in the daily amount of “Good On” time, defined as the sum of “On” time without dyskinesia and “On” time with non-troublesome dyskinesia. At the twentieth week, those who took IPX203 had an average of roughly half an hour more of “Good On” time compared with those who took immediate-release carbidopa/levodopa.In addition, a study published in the May 2022 Neurology found that 29.7% of patients who took IPX203 were “much improved” or “very much improved,” as evidenced in their scores on the Patient Global Impression of Change, compared with 18.8% of those who took immediate-release carbidopa/levodopa. ■“A Phase 3 Trial of IPX203 vs CD-LD IR in Parkinson’s Disease Patients with Motor Fluctuations (RISE-PD)” ISSUES NewArchived

Duration and impact of adverse events with esketamine nasal spray and quetiapine extended release in the ESCAPE-TRD phase IIIb trial

Duration and impact of adverse events with esketamine nasal spray and quetiapine extended release in the ESCAPE-TRD phase IIIb trial

Remission/response with esketamine nasal spray versus quetiapine extended release in treatment resistant depression using the Clinical Global Impression-Severity scale

Remission/response with esketamine nasal spray versus quetiapine extended release in treatment resistant depression using the Clinical Global Impression-Severity scale