FDA NewsPerspective

FDA approves esketamine nasal spray for hard-to-treat depression

The FDA has approved esketamine nasal spray, combined with an oral antidepressant, for the treatment of adults with treatment-resistant depression, according to a press release.

Due to safety concerns, esketamine nasal spray (Spravato, Janssen Pharmaceuticals) will only be available through a restricted distribution system under a Risk Evaluation and Mitigation Strategy (REMS) and must be administered in a certified medical office, according to the release.

This is the first FDA approval of esketamine for any use. This approval follows recommendations from the FDA Psychopharmacologic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee and positive data from multiple studies supporting esketamine nasal spray for patients with treatment-resistant depression.

"There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition," Tiffany Farchione, MD, acting director of the division of psychiatry products at the FDA's Center for Drug Evaluation and Research, said in the release. "Controlled clinical trials that studied the safety and efficacy of this drug, along with careful review through the FDA’s drug approval process including a robust discussion with our external advisory committees, were important to our decision to approve this treatment.”

Source: Adobe Stock

Labeling for esketamine nasal spray contains a boxed warning on the risk for sedation and dissociation; abuse and misuse; and suicidal thoughts and behaviors after administration. Patients must be monitored by a health care provider for at least 2 hours after receiving a dose, according to the release. Under REMS, prescribers and patients must sign a Patient Enrollment Form, and the drug must be dispensed with a patient Medication Guide outlining uses and risks.

Patients will self-administer esketamine nasal spray under in a certified clinic or doctor’s office under provider supervision, and the health care providers will determine when patients can leave after each use, according to the release.

“The approval of esketamine as a new medication for treatment-resistant depression is welcome news for people and their families who are impacted by depression,” Jeffrey Borenstein, MD, president and CEO of the Brain & Behavior Research Foundation, said in a press release. “We are pleased that the Brain & Behavior Research Foundation funding of both early research and ongoing studies on rapid-acting antidepressants has helped lead to this development of a new medication for treatment-resistant depression.”

The FDA has approved esketamine nasal spray, combined with an oral antidepressant, for the treatment of adults with treatment-resistant depression, according to a press release.

Due to safety concerns, esketamine nasal spray (Spravato, Janssen Pharmaceuticals) will only be available through a restricted distribution system under a Risk Evaluation and Mitigation Strategy (REMS) and must be administered in a certified medical office, according to the release.

This is the first FDA approval of esketamine for any use. This approval follows recommendations from the FDA Psychopharmacologic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee and positive data from multiple studies supporting esketamine nasal spray for patients with treatment-resistant depression.

"There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition," Tiffany Farchione, MD, acting director of the division of psychiatry products at the FDA's Center for Drug Evaluation and Research, said in the release. "Controlled clinical trials that studied the safety and efficacy of this drug, along with careful review through the FDA’s drug approval process including a robust discussion with our external advisory committees, were important to our decision to approve this treatment.”

Source: Adobe Stock

Labeling for esketamine nasal spray contains a boxed warning on the risk for sedation and dissociation; abuse and misuse; and suicidal thoughts and behaviors after administration. Patients must be monitored by a health care provider for at least 2 hours after receiving a dose, according to the release. Under REMS, prescribers and patients must sign a Patient Enrollment Form, and the drug must be dispensed with a patient Medication Guide outlining uses and risks.

Patients will self-administer esketamine nasal spray under in a certified clinic or doctor’s office under provider supervision, and the health care providers will determine when patients can leave after each use, according to the release.

“The approval of esketamine as a new medication for treatment-resistant depression is welcome news for people and their families who are impacted by depression,” Jeffrey Borenstein, MD, president and CEO of the Brain & Behavior Research Foundation, said in a press release. “We are pleased that the Brain & Behavior Research Foundation funding of both early research and ongoing studies on rapid-acting antidepressants has helped lead to this development of a new medication for treatment-resistant depression.”

    Perspective
    J. John Mann

    J. John Mann

    This is confirmation by the FDA that intranasal esketamine works as an antidepressant even in patients whose depression has not responded to two or more antidepressants in the past. Approval of esketamine is important for patients because other options like transcranial magnetic stimulation work more poorly in medication-resistant depression.

    Intranasal ketamine is not as reliably absorbed as IV ketamine, but many patients prefer to avoid an IV and most psychiatrists could give this drug intranasally in their office and provide medical supervision without needing to insert an IV. In short, this is a helpful alternative to the IV route of administration.

    We still need to figure out more clearly how many doses of ketamine should people get and what should the follow-up to ketamine treatment be in terms of medication, psychotherapy and other strategies. Also, what are the long-term safety characteristics of ketamine given in this way and whether we can develop medications that are even better than ketamine that work without producing the sort of “tripping effect” that people can get when they receive ketamine.

    The FDA decision is very good news for depressed patients, but we have more to learn about longer term use and safety of esketamine and ketamine.

    • J. John Mann, MD
    • Paul Janssen Professor of Translational Neuroscience (in psychiatry and radiology)
      Vice chair for research
      Department of psychiatry
      Columbia University

    Disclosures: Mann reports two NIH grants and one Brain & Behavior Research Foundation grant to fund work related to ketamine.