Can We Trust the FDA’s New Depression Approval?

Imagine waking up every day under a cloud that won’t lift.

The things you once loved no longer bring joy. Conversations feel like climbing a mountain, and simple tasks—getting dressed, making breakfast—seem insurmountable.

For millions with treatment-resistant depression, this is daily life.

Traditional antidepressants often fail these individuals. They endure weeks of trial and error, switching medications that might take months to show minimal improvement, all while battling debilitating side effects.

Now, a new breakthrough offers hope…

Esketamine (Spravato), recently approved by the FDA as a stand-alone therapy, promises faster relief for those trapped in the relentless cycle of depression.

Esketamine was first approved in 2019 as an add-on therapy for treatment-resistant depression and later expanded for severe depressive episodes paired with suicidal ideation.

This new approval allows its use without requiring oral antidepressants—a big deal for patients who struggle with the side effects and limited effectiveness of standard treatments.

In a trial involving 379 participants, esketamine showed promise:

• Patients saw significant improvements in depression scores by day 28.
• 22.5% achieved remission compared to just 7.6% in the placebo group.
• Some reported feeling relief within 24 hours—offering faster results than the typical 4–6 weeks for traditional antidepressants.

Dr. Gregory Mattingly, a trial investigator, praised the treatment’s ability to provide “freedom” for patients stuck on medications that yield “little benefit” but cause significant side effects.

While esketamine offers hope, it comes with a boxed warning for serious risks:

• Dissociation
• Respiratory depression
• Abuse and misuse
• Suicidal thoughts

Common side effects include dizziness, nausea, vomiting, feelings of drunkenness, and even increased blood pressure. For seniors and those with certain health conditions—like aneurysms or brain bleeds—this treatment isn’t suitable.

Given these risks, one can’t help but wonder: Did the FDA move too quickly? Historically, some approvals have resulted in recalls after unforeseen dangers emerged.

How thoroughly was esketamine studied before expanding its use?

This approval reflects a growing desperation to address treatment-resistant depression. Currently, a third of those with major depressive disorder don’t respond to oral medications, which often come with their own set of challenges:

• Weight gain
• Fatigue
• Insomnia
• Sexual dysfunction

If esketamine truly delivers relief where others fail, it could be a game-changer for the 21 million Americans battling depression. But we need more long-term data to determine its safety and effectiveness over time.

Here at e-Alert, we’ll be keeping a close eye on esketamine as more information emerges. If you or a loved one are struggling with depression, it’s worth discussing this option with your doctor—but proceed cautiously. Depression is a complex condition, and no single treatment is a magic bullet.

In the meantime, we’ll continue to push for greater transparency and accountability from the FDA. Patients deserve treatments that are not only effective but also thoroughly vetted for safety.

To staying informed, skeptical, and, as always, hopeful,

Rachel Mace
Managing Editorial Director, e-Alert
with contributions from the research team

P.S. Is this “bright” therapy the key to beating depression?

Sources:

Monaco, K. (2025, January 21). FDA Expands Approval of Esketamine for Depression. Medpagetoday.com; MedpageToday. https://www.medpagetoday.com/psychiatry/depression/113868

(2024, August 15). Managing Depression With Spravato (B. Simi, Ed.) [Review of Managing Depression With Spravato]. WebMD. https://www.webmd.com/depression/spravato-depression

Paul, A. (2025, January 22). FDA approves first-of-its-kind nasal spray for severe depression. Popular Science. https://www.popsci.com/health/spravato-fda-approval/

Berryhill, D. (2024, February 2). 9 Spravato Side Effects and Managing Them Long-Term. GoodRx. https://www.goodrx.com/spravato/spravato-side-effects?label_override=undefined

Berryhill, D. (2024, February 2). 9 Spravato Side Effects and Managing Them Long-Term. GoodRx. https://www.goodrx.com/spravato/spravato-side-effects?label_override=undefined