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FDA Approves J&J’s Spravato® as First Monotherapy for Treatment-Resistant Depression


On January 21, 2025, the U.S. Food and Drug Administration (FDA) approved Johnson & Johnson’s nasal spray, Spravato® (esketamine), to be used as a standalone treatment for adults with treatment-resistant depression (TRD). This groundbreaking decision marks the first time a medication for TRD has been approved as a monotherapy, expanding its potential use beyond its previous indication, which required pairing with oral antidepressants. Our Chief Medical Officer, Dr. Pabbati, stated that “the approval of Spravato as a monotherapy is a game-changer. It allows us to address individual patient needs more precisely while delivering its proven efficacy. This expanded option ensures that patients can benefit from Spravato without the added complexity of combining it with daily oral antidepressants.”

Understanding Treatment-Resistant Depression

Treatment-resistant depression affects individuals who have not responded adequately to at least two different traditional antidepressant medications. TRD is a particularly severe form of Major Depressive Disorder (MDD), which impacts around 21 million adults in the U.S. The condition can severely impair quality of life, leaving patients with limited treatment options. Managing TRD often requires innovative approaches beyond the standard use of serotonin and norepinephrine-targeting medications, which can take weeks to show benefits and may not work for everyone. (National Institute of Mental Health)

How Spravato® Works

Spravato® (esketamine) is a transformative approach to managing depression. Unlike traditional antidepressants, which primarily act on serotonin or norepinephrine pathways, esketamine targets the glutamate system, a key neurotransmitter involved in brain plasticity and connectivity. By increasing the levels of glutamate and dopamine, Spravato® promotes synaptic growth and restores neural pathways, leading to rapid and sustained improvements in mood and cognitive function. This mechanism is particularly crucial for patients requiring faster relief, especially those at high risk of suicide. (Headlight)

Clinical Evidence for Monotherapy Approval

The FDA’s decision to approve Spravato® as a monotherapy was supported by a Phase 4 clinical trial. The study demonstrated the nasal spray’s efficacy in significantly reducing depressive symptoms compared to a placebo. Patients treated with Spravato® reported improvements in symptoms as early as 24 hours after administration, with sustained benefits observed throughout the 28-day trial. By week four, 22.5% of participants achieved remission compared to 7.6% of placebo participants, underscoring its potential as a transformative treatment for TRD. (J&J Press Release)

Administration and Safety Measures

Spravato® is administered as a nasal spray in certified healthcare facilities. Following each dose, patients are closely monitored for at least two hours due to potential side effects, which include dissociation, dizziness, sedation, and a temporary increase in blood pressure. The supervised administration ensures patient safety and allows healthcare providers to manage any adverse reactions promptly. Each session is offered under the FDA- approved Risk Evaluations and Mitigation Strategy (REMS) program guidelines. (Reuters)

Impact on the Personalized Depression Treatments

The approval of Spravato® as a standalone therapy offers new opportunities for personalized treatment plans. This flexibility benefits patients who cannot tolerate or do not respond to traditional oral antidepressants, as well as those in need of rapid symptom relief. For clinicians, this monotherapy approval significantly broadens the spectrum of available interventions. (FDA Announcement)

Moving Forward

The FDA’s nod for Spravato® as a monotherapy represents a paradigm shift in how treatment-resistant depression is managed. As more healthcare providers adopt this approach, ongoing research will be critical to understanding its long-term safety and efficacy. For now, this approval offers renewed hope to patients and their loved ones, opening the door to better outcomes for those grappling with this debilitating condition.

At Headlight, we are excited to be part of this new frontier of innovation and see great potential in providing our clients with rapid relief from depression. This breakthrough allows us to offer hope and transformation for those who have struggled with traditional treatments, reaffirming our commitment to personalized, affordable, and accessible care.

More than 50% of Americans struggle with mental health.

Headlight is now collaborating with health plans and companies to make therapy more accessible and affordable. Speak to a Care Coordinator today.