Study supports effectiveness of esketamine nasal spray as fast-acting antidepressant

Study supports effectiveness of esketamine nasal spray as fast-acting antidepressant

Esketamine proves to be an immediate effective therapy for treating patients suffering from treatment-resistant depression (TRD), according to the results from a phase 3 trial of the drug. The study was published today in the American Journal of Psychiatry.

Unlike prior antidepressant drugs, esketamine is delivered intranasally as a spray instead of intravenous ketamine infusions. The drug takes effect within 24 to 48 hours so that the patients could have immediate relief. However, the nasal spray must be administered by a doctor, because it can temporarily leave patients with nausea, dizziness, and feelings of disassociation,said co-author Michael E. Thase, MD.

The drug esketamine (Spravato) was approved by the Food and Drug Administration (FDA) in March 2019, for treating patients with major depressive disorder who have not responded to other anti-depressant drugs. Esketamine nasal spray is approved to be used in conjunction with an oral antidepressant, for use in people with treatment-resistant depression.

Mood disorder pathophysiology has implicated abnormalities in glutamatergic transmission, along with disrupted function and structure in neural circuits involved in mood regulation.

Thus, glutamatergic N-methyl-D-aspartate (NMDA) receptor modulators have been investigated in treating depression.

Ketamine, an anesthetic and NMDA receptor antagonist, has shown potential role in the treatment of depression, with mood-elevating effects observed in previous studies. Intravenous ketamine administered at subanesthetic doses have found to exhibit rapid onset of efficacy in patients with treatment-resistant depression. However esketamine, the S-enantiomer of ketamine racemate, shows a higher affinity for the NMDA receptor than the R-enantiomer.

The phase 3 study required adult patients with treatment resistant depression to switch from their prior antidepressant to which they had not responded, to a newly prescribed oral anti-depressant plus either a varying dose of esketamine nasal spray or placebo nasal spray.

“This trial of esketamine was one of the pivotal trials in the FDA’s review of this treatment for patients with treatment resistant depression. Not only was adjunctive esketamine therapy effective, the improvement was evident within the first 24 hours,” Thase said. “The novel mechanism of action of esketamine, coupled with the rapidity of benefit, underpin just how important this development is for patients with difficult to treat depression.”

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