June 7, 2024

New Real-World Evidence Supports Esketamine Nasal Spray as an Effective Treatment for Treatment-Resistant Depression

Written by

L. Alison McInnes, MD, MS

Esketamine nasal spray offers a game-changing solution for those grappling with treatment-resistant depression, providing symptom relief after the first treatment, in contrast to traditional antidepressants that can take weeks or months of daily use to take effect.

While IV ketamine therapy preceded the development of esketamine, the latter is FDA-approved and covered by most insurance plans, making it a more accessible option for patients seeking fast-acting relief from their debilitating symptoms.

However, data on esketamine’s real-world effectiveness and optimal treatment duration is limited.

Two recent studies, presented by Dr. L. Alison McInnes and colleagues at the American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, shed light on the real-world use of ESK for TRD. See the full posters here.


Both studies leveraged data from Osmind, an electronic health record (EHR) designed to capture structured information from routine mental health visits. Patients were included if they were 18 years or older, had a diagnosis of MDD, received at least one ESK treatment, and had their first documented ESK treatment between March 5, 2019, and March 31, 2023. The primary outcome measure was the change in PHQ-9 score from baseline.

The first study assessed the impact of ESK treatment duration on depression symptoms using the PHQ-9 scale. The second study evaluated the effectiveness of ESK across various depression rating scales and explored comorbidities and concomitant medications in patients receiving ESK.


ESK treatment duration significantly impacted depression symptoms. The median number of treatments to initial response was 12 for the ESK-TRD group and 10 for the ESK all-comers group. Remarkably, response rates continued to increase beyond these timepoints, with 75% of the ESK-TRD cohort and 85% of the ESK all-comers cohort predicted to achieve response with persistence in treatment. Clinically significant reductions in depressive symptoms were observed after 12 treatments in the maintenance phase, suggesting that persistent ESK treatment yields added benefits for TRD patients.

The second study demonstrated the effectiveness of ESK across multiple depression rating scales, including PHQ-9, HRSD, BDI-II, QIDS-SR16, and MADRS. Over 75% of patients eventually responded to treatment, despite the presence of multiple comorbidities and polypharmacy. Anxiety disorders were the most common comorbid diagnosis, followed by trauma-related disorders and neurodevelopmental disorders. The majority of patients were also taking concomitant antidepressants and augmentation agents during ESK treatment.

Conclusion and Implications:

These real-world studies provide compelling evidence for the effectiveness of ESK in treating TRD, even in patients with complex clinical presentations. The findings suggest that continuing ESK treatment beyond the induction phase may offer additional benefits for patients with TRD, which is consistent with the results of the SUSTAIN-2 trial that reported a 79.6% sustained response rate with ongoing ESK treatment.

The high prevalence of comorbid conditions and polypharmacy among patients seeking ESK treatment highlights the importance of considering these factors when developing personalized treatment plans.

Summary of implications:
  • Continuing ESK treatment beyond the induction phase may provide additional benefits for TRD patients
  • Comorbid conditions and polypharmacy are common among patients seeking ESK treatment, emphasizing the need for personalized treatment plans
  • Further research is necessary to optimize treatment strategies, identify patients most likely to benefit from extended ESK therapy, and understand long-term outcomes

As the largest real-world studies of their kind, this research contributes to the growing body of evidence supporting the use of ESK for TRD. However, further research is needed to optimize treatment strategies, identify patients most likely to benefit from extended ESK therapy, and understand the long-term outcomes of ESK treatment.

Clinicians and Researchers: Let's chart the future of psychiatry, together

At Osmind, we harness the power of real-world data to drive evidence-based medicine and accelerate innovation in mental health. To explore more of our breakthrough research or to get involved, visit osmind.org/research and join us in our mission to transform mental healthcare.

Discover what’s next in mental health care. Join the Psychiatry Tomorrow newsletter.

Share this

Related Blog Posts

If you, or someone you know, is in crisis or needs immediate assistance, please call 911 immediately. To talk to someone now, please call the National Suicide Prevention Lifeline at 1-800-273-8255.

Osmind Inc. © 2024 All Rights Reserved.