The approval of esketamine, to be used in conjunction with an oral antidepressant, is a result of positive data coming from both short- and long-term clinical trials in which patients receiving the treatment demonstrated improvement in depression symptoms, as well as sustained improvement in symptoms. The nasal spray works by targeting the N-methyl-D-aspartate receptor, and ionotropic glutamate receptor in the brain.
“There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition,” said Tiffany Farchione, MD, acting director of the Division of Psychiatry Products in the Center for Drug Evaluation and Research at the FDA, in a statement. “Controlled clinical trials that studied the safety and efficacy of the 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.”
In 3 short-term studies, patients were randomized to receive either esketamine or a placebo nasal spray with an oral antidepressant. In one of the studies, esketamine resulted in statistically significant improvement in the severity of depression, with some effects prevalent within 2 days. However, the other 2 trials did not meet the pre-specified statistical tests for demonstrating effectiveness. During the long-term trial, patients who were in stable remission or had stable response and continued treatment with esketamine had a significantly longer time to relapse of depressive symptoms.
“Spravato has the potential to change the treatment paradigm and offer new hope to an estimated one-third of people with major depressive disorder who have not responded to existing therapies,” said Mathai Mammen, MD, PhD, global health, Janssen Research & Development, in a statement.
Because of the risk of serious adverse events caused by the treatment, as well as the risk for misuse and abuse of the treatment, once esketamine is indicated for a patient, the patient will self-administer the treatment at a certified treatment center under the advisement of a provider. The most commonly reported side effects of the treatment include nausea, vertigo, anxiety, lethargy, and increased blood pressure.
The approval comes weeks after an FDA advisory panel endorsed the treatment, voting 15-2 in favor of the drug.