Efficacy of Esketamine Nasal Spray for TRD in Real-World Clinical Settings


How effective is this treatment in real-world clinical settings? Experts explore this in a poster presented at the 2024 ASCP Annual Meeting.




A poster at the 2024 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting discussed a study exploring the effectiveness of esketamine nasal spray for patients with treatment-resistant depression (TRD) in real-world clinical settings.1

Major depressive disorder (MDD) affects millions of adults worldwide, according to the study’s investigators, with approximately 30% of these individuals experiencing TRD. TRD is characterized by the failure to respond to at least 2 different antidepressant trials of adequate dose and duration.2 Esketamine nasal spray, which was approved by the US Food and Drug Administration (FDA) for TRD in 2019, represents a novel therapeutic option. However, real-world data on its effectiveness has been limited.1

In the study, investigators conducted a retrospective observational analysis of depression outcomes among patients with MDD who received esketamine treatment. The analysis included 2 cohorts: the ESK all-comers cohort (664 patients) and the ESK-TRD cohort (361 patients). The ESK-TRD cohort was specifically defined as those who had tried at least 2 different antidepressants within 2 years prior to esketamine treatment. Depression severity was measured using the Patient Health Questionnaire-9 (PHQ-9), administered within 30 days before and after esketamine treatment.1

The ESK-TRD cohort had a mean age of 45 years, with 64% being female and 95% identifying as White. Patients typically had moderately severe depression at baseline (mean PHQ-9 score of 17) and had tried an average of 3 different antidepressants. Co-occurring psychiatric conditions were common, with 74% of patients diagnosed with anxiety disorders and 29% with trauma- and stressor-related disorders.1

In the ESK-TRD cohort, 71% of patients completed the induction phase, defined as at least 8 treatments within 42 days. The outcomes analysis demonstrated significant reductions in PHQ-9 scores following esketamine treatment. Reductions were noticeable after just 1 treatment, with PHQ-9 scores decreasing by more than 4 points after 5 to 8 treatments, and by more than 5 points after 13-16 treatments.1

The investigators concluded that esketamine nasal spray is associated with significant reductions in depression symptoms for patients with TRD in real-world clinical settings. These improvements were observed as early as after the first treatment and continued to increase with subsequent treatments. The findings align with previous clinical trial results, reinforcing the potential of esketamine as a viable option for individuals struggling with TRD. The investigators suggested that future research explore the long-term benefits and optimal use of esketamine in diverse patient populations.1

The poster was presented by study co-author Lynne McInnes, MD, of Osmind.

Are you interested in learning more about the latest research, treatments, and other clinical issues associated with treatment-resistant depression? Here are some recent updates as seen in Psychiatric Times®:

Augmentation Strategies for Treatment-Resistant Depression

Managing Suicidal Thoughts, Behaviors, and Risk in Treatment-Resistant Depression

Treatment-Resistant Geriatric Depression: Augmenting or Switching an Antidepressant

Managing Treatment-Resistant Depression: Tips for the Outpatient Psychiatrist

Psychotherapy for Treatment-Resistant Depression Is Overlooked, Underused

Single-Dose Psilocybin for Treatment-Resistant Major Depression

Study Finds Esketamine Nasal Spray More Likely to Induce Remission in Treatment-Resistant MDD Than Quetiapine Extended Release

Hope and Healing for Patients With Treatment-Resistant Depression

Potentially Treatable Metabolic Abnormalities in Patients with Treatment-Resistant Depression

BPL-003: Rapid, Durable Treatment for TRD Sees Positive Phase 2 Results

Stay up-to-date on news related to research on promising new interventions and developments in the treatment of a wide variety of psychiatric disorders at psychiatrictimes.com.

Note: This article was prepared with the assistance of ChatGPT.


1. McInnes L, Joshi K, Kane G, et al. A retrospective study of real-world clinical effectiveness of esketamine nasal spray therapy among patients with treatment resistant depression. American Society of Clinical Psychopharmacology Annual Meeting. Poster presentation. May 30, 2024. Accessed May 30, 2024.

2. McIntyre RS, Alsuwaidan M, Baune BT, et al. Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventionsWorld Psychiatry. 2023;22(3):394-412.

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