FDA Approves First Nasal Spray Monotherapy for Treatment-Resistant Depression with One-Month Efficacy

Recently, Johnson & Johnson announced that the FDA has approved the supplemental New Drug Application (sNDA) for esketamine CIII nasal spray, making it the first and only monotherapy for the treatment of adult patients with major depressive disorder (MDD) who have had an inadequate response to at least two oral antidepressants. That is to say,Esketamine is the first monotherapy approved in the United States for the treatment of adults with treatment-resistant depression (TRD).

▍About Refractory Depression

Approximately one-third of patients with severe depression do not respond to oral antidepressants, a condition known as treatment-resistant depression, which is defined as a poor response to two oral medications. Patients typically try multiple oral medications and wait 4-6 weeks for potential relief. After trying a third oral antidepressant, approximately 86% of patients still do not achieve remission.

Aripiprazole, Brexpiprazole, Quetiapine, and Cariprazine have been approved by the FDA., can be used as an adjunctive treatment after insufficient response to antidepressants,The combination of olanzapine and fluoxetine has also been approved for the TRD indication., specifically according to the prescription label (i.e., patients who have not responded after using two different antidepressants for at least 6 weeks during the current episode, and patients who have not responded after using two different antidepressants for at least 6 weeks during the current course of illness with doses reaching or exceeding the labeled minimum effective dose).

In addition to the atypical antipsychotic drugs approved by the FDA discussed above,LurasidonePhase 3 trials are currently underway, and lurasidone has been shown to be effective for MDD with mixed features.

Moreover,Ziprasidone and RisperidoneAs an adjunctive treatment for MDD patients with inadequate response to antidepressant therapy, there are also positive research outcomes.

▍About Esketamine

Esketamine is an NMDA receptor antagonist that works by targeting glutamate, the most abundant excitatory neurotransmitter in the brain.In 2019, Esketamine was approved for marketing in the United States and used in combination with oral antidepressants to treat refractory depression.

This therapy has been approved by the U.S. FDA for use in combination with oral antidepressants to treat adults with TRD and MDSI (Major Depressive Disorder with Acute Suicidal Ideation or Behavior). In April 2023, the drug was approved in China for alleviating depressive symptoms in adult patients with major depressive disorder accompanied by acute suicidal ideation or behavior when used in conjunction with oral antidepressants.

EsketamineThe approval of this indicationBased on the positive results of a randomized, double-blind, multicenter, placebo-controlled study. The study showed that esketamine alone demonstrated faster and superior improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) total score compared to placebo.

In the post-hoc analysis, esketamine showed numerical improvement in all 10 MADRS items at Day 28. At Week 4, 7.6% of patients in the placebo group achieved remission (MADRS total score ≤12), compared to 22.5% of patients in the esketamine group.

Source: PharmaCube Info, Medical Light