Adjunctive Intranasal Esketamine Eases Treatment-Resistant Depression
By Megan Brooks
NEW YORK—In patients with treatment-resistant depression (TRD), twice-weekly intranasal esketamine added to oral antidepressant therapy produced rapid and meaningful improvement in depressive symptoms in a phase 2 double-blind, randomized, placebo-controlled trial.
Dr. Ella Daly, of the Department of Neuroscience, Janssen Research & Development in Titusville, New Jersey, and colleagues reported the findings online December 27 in JAMA Psychiatry.
“The results of the study by Daly and colleagues demonstrate the considerable promise of combining a compound with rapid antidepressant effects with intranasal delivery,” write Dr. Daniel Quintana and colleagues from University of Oslo, Norway, in a linked editorial.
Dr. Daly and colleagues tested 28-mg, 56-mg, and 84-mg doses of esketamine nasal spray given twice weekly as an adjunct to existing oral antidepressant therapy in 67 patients with TRD.
All three doses of esketamine produced a rapid antidepressant effect superior to placebo, as evidenced by significant changes in the Montgomery-Asberg Depression Rating Scale (MADRS) total score. The score declines were -4.2, -6.3 and -9.0 for the 28-mg, 56-mg and 84-mg doses, respectively.
“Improvement in depressive symptoms persisted over the open-label phase, despite reduced dosing frequency, and for up to 2 months after cessation of esketamine dosing,” the investigators note.
The three esketamine doses appeared to be safe, with no new or unexpected safety concerns, they note.
Dr. Quintana and colleagues say it is “reassuring to learn that no psychotic symptoms were observed in the trial; however, patients with psychotic disorders or major depressive disorder with psychosis were excluded from the study. One of the 3 most common adverse effects was perceptual changes or dissociative symptoms, which fits with the known effect of ketamine and should be further clarified before starting routine use in clinical practice,” they write. In addition, several issues related to long-term use, including the potential for addiction and adverse effects, need to be carefully assessed in future studies, they say.
“Given the early stages of research in esketamine treatment of depression, it is important to be cautious. We look forward to further research developments of intranasal esketamine as a novel treatment for depression given the crucial need for better antidepressants,” write Dr. Quintana and colleagues.
"About one third of patients with major depressive disorder do not respond to current treatment options," Dr. Husseini Manji, Janssen's Global Head of Neuroscience Therapeutic Area, said in a news release. "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. 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."
“Phase 3 studies in treatment-resistant depression are ongoing and we are working on finalizing those studies now,” Dr. Daly told Reuters Heath by email.
The study was funded by Janssen Research & Development, LLC, which employs eight of the authors.
SOURCES: https://bit.ly/2BKVXPO and https://bit.ly/2lQ38jV
JAMA Psychiatry 2017.
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