FDA Approves Ketamine as a Monotherapy for Treatment-Resistant Depression

As a practicing psychiatric clinician at a clinic in Scottsdale providing ketamine therapy, I am excited to share recent advancements in the treatment of major depressive disorder (MDD). The U.S. Food and Drug Administration (FDA) has recently approved SPRAVATO® (esketamine) nasal spray as a standalone therapy for adults with treatment-resistant depression (TRD) (Johnson & Johnson, 2025). I believe that this approval is vindication for early adopters like our clinic who have witnessed and attested to the tremendous benefits of Ketamine in well-selected patients.

The FDA's approval of SPRAVATO® (esketamine) as the first monotherapy for treatment-resistant depression represents a groundbreaking advancement in mental health care, offering rapid symptom relief through a novel mechanism targeting the glutamate system. This approval, along with ongoing developments in ketamine-based therapies, underscores the growing potential of innovative treatments for individuals who have not responded to traditional antidepressants.

Understanding Treatment-Resistant Depression

TRD is characterized by the failure to achieve adequate response from at least two different oral antidepressants. This condition affects a significant portion of individuals diagnosed with MDD, presenting substantial challenges for both patients and healthcare providers (Johnson & Johnson, 2025).

What is SPRAVATO® (Esketamine)?

SPRAVATO® is a nasal spray formulation of esketamine, a derivative of ketamine. Unlike traditional antidepressants that primarily target monoamine neurotransmitters, esketamine modulates the glutamate system, offering a novel approach to depression treatment (Johnson & Johnson, 2025).

Clinical Evidence Supporting Monotherapy Approval

The FDA's decision was based on compelling clinical data demonstrating SPRAVATO®'s efficacy as a monotherapy. In clinical trials, patients receiving SPRAVATO® experienced rapid and significant improvements in depressive symptoms compared to placebo, with benefits observed as early as 24 hours post-administration (Johnson & Johnson, 2025).

Administration and Safety Considerations

Due to its potential for misuse and the necessity for monitoring, SPRAVATO® is administered in certified healthcare settings under professional supervision. Common side effects include dizziness, nausea, increased blood pressure, and dissociation. It is crucial for providers to assess each patient's suitability for this treatment and to monitor them closely during and after administration (Johnson & Johnson, 2025).

Implications for Clinical Practice

The approval of SPRAVATO® as a monotherapy offers a new option for patients with TRD who have not benefited from traditional antidepressants. Its rapid onset of action is particularly beneficial for individuals experiencing severe depressive episodes. As with any treatment, it is essential to weigh the benefits against potential risks and to engage in shared decision-making with patients.

Additional Insights from other Peer-Reviewed Studies

Recent research has further explored the efficacy of ketamine and its derivatives in treating TRD. A review highlighted that a single subanesthetic-dose intravenous ketamine infusion can rapidly improve depressive symptoms in individuals with MDD and bipolar depression, with effects lasting several days (Coyle & Laws, 2022). Another study found that after three ketamine infusions over 11 days, 52% of participants achieved remission from severe depression (Murrough et al., 2022). These findings underscore the potential of ketamine-based therapies as rapid-acting antidepressants.

About the Author

Dr. David George is a psychiatric provider and the clinical director of Neuregen, an integrative psychiatry and neurologic health center based in Scottsdale, Arizona that has been an early adopter in the therapeutic use of ketamine, refining its application to ensure safe and effective patient outcomes. Dr. George and his team are dedicated to advancing innovative, evidence-based treatments for patients facing complex mental health challenges. The introduction of SPRAVATO® monotherapy aligns with our mission to offer effective solutions for those battling treatment-resistant depression.

References

Coyle, C. M., & Laws, K. R. (2022). Ketamine treatment for depression: a review. Frontiers in Psychiatry, 13, 901039. https://doi.org/10.3389/fpsyt.2022.901039

Johnson & Johnson. (2025, January 21). SPRAVATO® (esketamine) approved in the U.S. as the first and only monotherapy for adults with treatment-resistant depression. Johnson & Johnson. Retrieved from https://www.jnj.com/media-center/press-releases/spravato-esketamine-approved-in-the-u-s-as-the-first-and-only-monotherapy-for-adults-with-treatment-resistant-depression

Murrough, J. W., et al. (2022). Ketamine's promise for severe depression grows, but major questions remain. Journal of Affective Disorders, 299, 620-627. https://doi.org/10.1016/j.jad.2021.12.098