A ketamine-based nasal spray produces rapid improvement of depressive symptoms, according to new research published in the scientific journal JAMA Psychiatry.

The double-blind, randomized, placebo-controlled study of 67 adults with a diagnosis of major depressive disorder examined the effects of esketamine, a component of the general anesthetic ketamine.

“Depression is the number one cause of disability worldwide,” remarked study author Ella J. Daly, a researcher at Janssen Pharmaceutical Companies.

“The development of a novel, safe and effective treatment for patients suffering from treatment-resistant depression (TRD) is a recognized significant unmet medical need,” Daly told PsyPost.

“Currently, about one third of patients with major depressive disorder do not respond to treatment with conventional antidepressant medications, leading to continued suffering for patients and their families and significant direct and indirect costs to society. In the US alone, it is estimated that there are approximately 6 million people with treatment resistant depression.”

Previous research had found that ketamine produced an antidepressant effect in patients with treatment-resistant major depressive disorder. Ketamine interacts with NMDA receptors in the brain, meaning it works differently than conventional antidepressant medications that influence serotonin.

The new study, which was a Phase 2 clinical trial, tested disposable nasal spray devices that delivered a dose of esketamine.

“The intranasal formulation that we are studying is less invasive compared to an intravenous formulation, and may facilitate ease of access in outpatient settings,” Daly explained.

In the study, the participants received 28-mg, 56-mg, and 84-mg doses of esketamine twice weekly. All three doses produced an antidepressant effect. The participants were given esketamine in addition to their currently existing antidepressant treatment.

The drug was generally well-tolerated. But four participants experienced adverse effects that led them to drop out of the study. The most common adverse effects were dizziness, headache, and dissociative symptoms.

“Intranasal esketamine is being developed as a treatment for adults with treatment-resistant depression (TRD). Ongoing phase 3 studies are under way to demonstrate safety and efficacy and to better understand the optimal duration of treatment,” Daly said.

“Of note, in a separate program, Janssen is also evaluating intranasal esketamine as a treatment for patients with major depressive disorder and imminent suicidality.”

The study was funded by Janssen Research & Development, which hopes esketamine will become a medically-approved treatment.

“The results of this study reinforce the potential of esketamine as a treatment for patients with treatment-resistant depression and support further clinical research, providing hope for people in need,” Daly said.

“If approved by the FDA, esketamine would be one of the first new approaches to treat refractory major depressive disorder available to patients in the last 50 years.”

The study, “Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression A Randomized Clinical Trial“, was co-authored by Jaskaran B. Singh, Maggie Fedgchin, Kimberly Cooper, Pilar Lim, Richard C. Shelton, Michael E. Thase, Andrew Winokur, Luc Van Nueten, Husseini Manji, and Wayne C. Drevets.

