FDA Approves Nasal Spray to Treat Depression in Adults

Earlier this month, FDA announced the approval of Spravato (esketamine) nasal spray.  The product is to be used in conjunction with an oral antidepressant and is indicated for the treatment of depression in adults suffering from treatment-resistant depression.

In a recent statement, Tiffany Farchione, M.D., acting director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research (CDER), stated that “there has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition.”

Esketamine is the s-enantiomer of ketamine, the mixture of two enantiomers (mirror image molecules). Ketamine was approved by the FDA in 1970, but this is the first FDA approval of esketamine for any use. According to an article from NBC News, drugmakers believe that Spravato can help 30 – 40% of patients who do not respond to antidepressants. The nasal spray works faster than other known treatments and has displayed benefits four hours after use.

Treatment-Resistant Depression

According to the World Health Organization (WHO), depression affects 300 million people worldwide. A study conducted in 2018 from the NCHS displayed that, between 2013 and 2016, 8.1% of American adults above the age of 20 had suffered from depression in a given two-week period. Patients with treatment resistant depression have major depressive disorder and have not responded to at least two antidepressant treatments given at adequate doses for an adequate duration of the current episode. It has been reported that one third of patients with depression experience treatment resistant depression.

Clinical Trials

The efficacy of Spravato was evaluated in three clinical trials spanning four-week time spans, and one longer-term maintenance-of-effect trial. Patients participating in the trials were selected to randomly receive either Spravato or a placebo. To maintain the need for some patients to receive some sort of treatment, all patients started a new oral antidepressant which continued throughout the trials. The primary efficacy measure of the trials was the change on a scale from the baseline to assess the severity of depressive symptoms.

According to FDA’s press release, “in one of the short-term studies, Spravato nasal spray demonstrated statistically significant effect compared to placebo on the severity of depression, and some effect was seen within two days. The two other short-term trials did not meet the pre-specified statistical tests for demonstrating effectiveness. In the longer-term maintenance-of-effect trial, patients in stable remission or with stable response who continued treatment with Spravato plus an oral antidepressant experienced a statistically significantly longer time to relapse of depressive symptoms than patients on placebo nasal spray plus an oral antidepressant.”

Side effects reported during the clinical trial were disassociation, dizziness, nausea, sedation, vertigo, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, vomiting and feeling drunk.

Administering Spravato

“The Spravato labeling contains a Boxed Warning that cautions that patients are at risk for sedation and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after administration of the drug.  Because of the risk of serious adverse outcomes resulting from sedation and dissociation caused by Spravato administration, and the potential for abuse and misuse of the drug, it is only available through a restricted distribution system, under a Risk Evaluation and Mitigation Strategy (REMS).”

Patients may self-administer the nasal spray in a certified medical office, however, due to the sedation effect, must be monitored by a health care provider for at least two hours after receiving the medication. Under REMS, a Patient Enrollment form must be signed by the prescriber and patient, which specifies that patients must make arrangements not to drive or operating heavy machinery for the remainder of the day after they receive the drug.

On Tuesday, March 5^th, FDA grated Fast Track and Breakthrough Therapy designations to Janssen Pharmaceuticals, Inc. for the Spravato application.  This is a huge step for the treatment of depression and is expected to have a positive impact on the lives of individuals suffering from treatment-resistant depression.

Are you in the process of developing a product that may be eligible for one of FDA’s expedited approval programs? We can help determine whether your product meets FDA’s guidelines and assist as you move through the approval process.  To learn more about our services and how we can help you achieve successful interactions with FDA, contact us today.