Spravato (esketamine intranasal) / J&J - LARVOL DELTA

Short-term ketamine interventions for depressive disorders: practical best-practice recommendations for psychiatrists using oral, subcutaneous, and nasal formulations. (PubMed, Front Psychiatry) - "Oral ketamine may be considered when parenteral or regulated nasal options are inaccessible, but it requires cautious patient selection, controlled dispensing, and objective monitoring. Esketamine nasal spray should follow the approved product label where available, whereas compounded racemic nasal ketamine should be reserved for exceptional circumstances."

Journal • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Esketamine for treatment of depression in Huntington's disease: A case report. (PubMed, J Huntingtons Dis) - "In a three-month follow-up investigation depression worsened again (BDI score: 20). To our knowledge, this is the first reported case of esketamine use in HD, suggesting that esketamine may be a treatment option for psychiatric symptoms in HD, particularly treatment-resistant depression."

Journal • CNS Disorders • Depression • Huntington's Disease • Mood Disorders • Movement Disorders • Psychiatry • Suicidal Ideation

The effect of dexmedetomidine versus saline placebo combined with esketamine on postpartum depression in patients undergoing cesarean section (ChiCTR) - P=N/A | N=306 | Not yet recruiting | Sponsor: Women and Children's Medical Center Affiliated to Guangzhou Medical University; Women and Children's Medical Center Affiliated to Guangzhou Medical Un | Initiation date: Feb 2026 ➔ Jul 2026

Trial initiation date • CNS Disorders • Depression • Mood Disorders • Postpartum Depression • Psychiatry

Prophylactic Use of Intranasal Esketamine Against Cumulative Perioperative Anxiety in Pediatric Patients with Two Consecutive Surgeries (ChiCTR) - P=N/A | N=141 | Not yet recruiting | Sponsor: Plastic Surgery Hospital，Peking Union Medical College Chinese Academy of Medical Sciences; Plastic Surgery Hospital，Peking Union Medical College Chine

New trial • Mood Disorders • Pediatrics • Psychiatry

Study on the Efficacy and EEG Characteristics of Dexmedetomidine Combined with Esketamine in the Treatment of Adolescent Major Depressive Disorder (ChiCTR) - P=N/A | N=60 | Not yet recruiting | Sponsor: Guabgzhou First People‘s Hospital; Guabgzhou First People‘s Hospital

New trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Real-World Effectiveness and Safety of Esketamine Nasal Spray in Treatment-Resistant Depression: A Retrospective Observational Study. (PubMed, Healthcare (Basel)) - "Background/Objectives: This study evaluated the real-world effectiveness and safety of intranasal esketamine plus oral antidepressants compared with venlafaxine-based oral antidepressant therapy in adults with moderate-to-severe treatment-resistant depression (TRD). In this retrospective routine care cohort, esketamine was used in patients with more complex TRD and was associated with modestly lower matched follow-up PHQ-9 scores. The observational design, baseline imbalance, and attrition precluded causal conclusions."

Journal • Observational data • Real-world evidence • Retrospective data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Sexual Disorders

Fentanyl OR Esketamine for Traumatic PAIN (FORE-PAIN) Trial (clinicaltrials.gov) - P3 | N=235 | Terminated | Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | N=608 ➔ 235 | Trial completion date: Mar 2026 ➔ Aug 2026 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2026 ➔ Aug 2026; slow recruitment.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Mood Disorders • Pain

Beyond symptom reduction: Intranasal esketamine is associated with improved quality of life in treatment-resistant depression. (PubMed, J Psychiatr Res) - "Intranasal esketamine was associated with significant improvements in depressive symptoms, hopelessness, suicidal ideation, and quality of life over 6 months in patients with TRD, with no statistically significant differences detected across antidepressant subgroups in this exploratory comparison."

HEOR • Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry • Suicidal Ideation

Real-world clinical practice, effectiveness and safety of esketamine nasal spray in major depressive disorder patients: a French prospective cohort (ELLIPSE study). (PubMed, Ther Adv Psychopharmacol) - "This real-world study in patients with treatment-resistant depression, including those with comorbidities/prior suicide attempts, showed clinically relevant improvement from month 2, sustained through 12 months. Dissociative symptoms were the most frequent treatment-related AE."

Journal • Real-world evidence • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Esketamine-based treatment, depression-specific metacognitive training, and their combination in treatment-resistant depression: 6-month trajectories of depressive symptoms and rumination in a multicenter observational study. (PubMed, Eur Arch Psychiatry Clin Neurosci) - "Concomitant treatment profiles showed marked imbalance in previous non-pharmacological treatment exposure, representing an important potential confounder. Findings support a cautious, hypothesis-generating interpretation because allocation was nonrandomized, assessment was open-label, the sample was modest, and baseline rumination was higher in the combined group."

Journal • Observational data • CNS Disorders • Depression • Mood Disorders • Psychiatry

Psychedelics in psychiatry: comparative effectiveness, implementation, commercialization and safety lessons learned from intranasal esketamine. (PubMed, Expert Opin Drug Saf) - No abstract available

HEOR • Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Echo: results from a non-interventional cohort study of esketamine nasal spray in treatment resistant depression (WFSBP 2026) - "ECHO is the first large prospective real-world evidence study of ESK-NS in TRD, with a broader patient population than previously studied. Data will enhance understanding of real-world ESKNS use, which may improve guidance and treatment strategies for patients with TRD. [1] Spravato SmPC."

CNS Disorders • Depression • Mood Disorders • Psychiatry

Implementation and use of risk minimization control tools in the EU: A multistakeholder survey. (PubMed, Br J Clin Pharmacol) - "RMCT implementation was generally perceived as feasible, although regulatory implementation was more challenging than integration into healthcare. Successful implementation may benefit from flexible design, alignment with existing systems, feasibility assessment, stakeholder engagement and clear guidance."

Journal

Case report of S-ketamine as treatment option for suicidal ideation and treatment-resistant depression in adolescents with early-onset psychosis. (PubMed, Neuropsychiatr) - "This case suggests that intranasal S‑ketamine may be a safe and effective augmentation strategy for TRD and suicidality in stable adolescent early-onset psychosis, highlighting the need for further research in this high-risk population."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry • Schizophrenia • Suicidal Ideation

Therapeutic Potential of Ketamine in Major Depressive Disorder: Pharmacological Insights and Clinical Evidence. (PubMed, Curr Pharm Des) - "When conventional treatments are ineffective for treating treatment-resistant depression, ketamine offers quick and strong results, marking a paradigm change in psychiatric care. To optimise longitudinal dosage regimens, assess long-term safety profiles, and develop next-generation analogues that maintain neuroplastic benefits while reducing side effects, further investigation is necessary."

Journal • Cardiovascular • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Profiling intranasal esketamine for adults with major depressive disorder and acute suicidal ideation or behavior: a phenotype-informed drug profile. (PubMed, Expert Rev Neurother) - "Esketamine should be used within its regulatory indication as one component of supervised, multimodal emergency care. The phenotype framework proposed here is hypothetical, intended to generate prospective research questions, and not a validated basis for individual treatment selection."

Journal • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Pain • Psychiatry • Suicidal Ideation

A Systematic Review of Long-term Safety Outcomes of Ketamine and Esketamine in Patients with Treatment-resistant Depression. (PubMed, Psychother Psychosom) - "Current evidence supports the safety of ketamine and esketamine for TRD, with no cumulative organ toxicity or iatrogenic addiction during maintenance treatment. Acute effects remain transient and manageable. However, findings are limited by heterogeneity in safety monitoring across studies."

Journal • Review • Anesthesia • Cardiovascular • CNS Disorders • Cognitive Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Suicidal Ideation

(Es)ketamine: practice update (PubMed, Nervenarzt) - "Ketamine has been established as an anesthetic agent for decades. Esketamine is approved exclusively in combination with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) and requires administration in a specifically structured setting with defined monitoring. This article provides a practice-oriented update on the mechanism of action, indications, contraindications, the approved treatment regimen, safety requirements and the positioning within the therapeutic algorithm."

Journal • Anesthesia • CNS Disorders • Depression • Psychiatry

Intranasal esketamine for ECT-refractory bipolar depression: a case report. (PubMed, Front Psychiatry) - "She tolerated the treatment well with minimal side effects and no reported manic or hypomanic events. More robust research is warranted to better characterize the effectiveness of esketamine in treating treatment-resistant bipolar depression."

Journal • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

Psychoactive and Neurobiological Effects of Ketamine in Humans: A Scoping Review of Clinical Evidence. (PubMed, J Clin Med) - "Intravenous racemic ketamine was the most extensively investigated administration route, while intranasal esketamine represents the primary approved formulation for TRD. However, information regarding long-term efficacy and safety remains limited due to study heterogeneity, short follow-up periods, and variability in dosing protocols. Further research is needed to address gaps related to long-term outcomes, maintenance strategies, and optimal dosing approaches."

Journal • Review • CNS Disorders • Depression • Mental Retardation • Psychiatry • Suicidal Ideation

PoET: Positioning of Esketamine Treatment in the Real-world Management of Depression (clinicaltrials.gov) - P4 | N=162 | Recruiting | Sponsor: Royal North Shore Hospital | Trial completion date: Jan 2026 ➔ Aug 2028 | Trial primary completion date: Sep 2025 ➔ Dec 2027

Real-world evidence • Trial completion date • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Emerging Clinical Applications of Ketamine and Esketamine Across Psychiatric Disorders. (PubMed, Focus (Am Psychiatr Publ)) - "In this review, the authors describe recent advances in the use of ketamine and esketamine for the treatment of depression and other psychiatric disorders, new research on novel treatment targets, and emerging evidence about ketamine's potential as a prophylactic intervention. Key outstanding issues and limitations of current ketamine treatment also are discussed."

Journal • Review • CNS Disorders • Depression • Mental Retardation • Mood Disorders • Psychiatry

Effect of Esketamine on Depressive Symptoms in Adolescents With Major Depressive Disorder at Imminent Suicide Risk: A Randomized Psychoactive-Controlled Study. (PubMed, Focus (Am Psychiatr Publ)) - "Combined 56- and 84-mg doses of esketamine were superior to midazolam in reducing depressive symptoms at 24 hours following the first dose; all 4 treatment groups showed continued improvement in depressive symptoms and severity of suicidality after 4 weeks of treatment. The most common side effects reported for esketamine-treated participants were dizziness, nausea, dissociation, headache, bitter taste, and sleepiness.Appeared originally in J Am Acad Child Adolesc Psychiatry 2026; 65:42-55."

Clinical • Journal • CNS Disorders • Depression • Major Depressive Disorder • Pain • Psychiatry

Last resort: the ethical obligation to offer ketamine in psychiatric euthanasia and assisted suicide. (PubMed, J Med Ethics) - "Intravenous ketamine and intranasal esketamine have shown rapid effects in reversing suicidality and improving depressive symptoms...Ketamine can both help clarify patients' decision-making capacity and serve as a reasonable therapeutic alternative when determining irremediability. For patients who refuse potentially effective treatments such as ketamine, oversight bodies should establish a formal process through which they can petition for review of their EAS request-protecting their legal right to die while guarding against potentially preventable death."

Journal • CNS Disorders • Psychiatry • Suicidal Ideation

A Study of Esketamine Nasal Spray Versus Placebo Spray in Adult Participants With Treatment-resistant Depression (clinicaltrials.gov) - P3 | N=348 | Recruiting | Sponsor: Janssen Research & Development, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • CNS Disorders • Depression • Mood Disorders • Psychiatry