MIAMI — In a new study, a statistically significant and clinically meaningful treatment effect was seen in patients aged 65 to 74 years who had treatment-resistant depression (TRD) when esketamine nasal spray was added to their oral antidepressant in comparison with patients treated with placebo plus an oral antidepressant.
"The need for an effective antidepressant agent to treat treatment-resistant depression in the elderly is great," Rachel Ochs-Ross, MD, Janssen Research and Development, LLC, Titusville, New Jersey, told Medscape Medical News.
"In this age group, you have people who are very depressed, and they get ECT [electroconvulsive therapy] five times more frequently than younger patients, because their treatment options are so limited. So there is definitely a need for a medication that is effective and safe in this population," said Ochs-Ross.
The study was presented here at the American Society of Clinical Psychopharmacology (ASCP) 2018 annual meeting.
First Large Trial
"This is the first large clinical trial of esketamine nasal spray in the elderly. No one knew if it could be completed or not. The study was different from other studies because it's not actually a placebo control," Ochs-Ross said.
"All subjects had to take a new oral antidepressant that they have not been treated with in the current episode of depression. So patients either got a new oral antidepressant plus a placebo spray or a new oral antidepressant plus nasal esketamine spray," she said.
The study included 138 patients (mean age, 70 years; SD, 4.52) who were randomly assigned to receive either eskatamine nasal spray plus an antidepressant (n = 72) or placebo nasal spray plus an antidepressant (n = 66).
For patients in the esketaime group, the starting dose was 28 mg. The dose was increased to 56 mg, and by the end of the study, patients were receiving 84 mg, which was well tolerated, Ochs-Ross said.
The trial's primary efficacy endpoint was change from baseline to day 28 in total score on the Montgomery-Åsberg Depression Rating Scale (MADRS).
At baseline, the mean MADRS total score was 35.2 (SD, 6.16).
At day 28, the mean change in MADRS total score from baseline was -10.0 (SD, 12.74) for the esketamine-plus-antidepressant group and -6.3 (SD 8.86) for the placebo-plus-antidepressant group (P = .029).
"The higher esketamine dose was tolerated equally well in these older patients as in younger patients," Ochs-Ross said.
The most common adverse events seen in the esketamine group were dizziness (20.8%), nausea (18.1%), headache (12.5%), fatigue (12.5%), increased blood pressure (12.5%), vertigo (11.1%), and dissociation (11.1%).
In the placebo group, the most common adverse events were anxiety (7.7%), dizziness (7.7%), and fatigue (7.7%).
"While treatment with esketamine plus an antidepressant did not demonstrate a statistically significant difference vs placebo plus an antidepressant on the MADRS score at day 28, which was our primary outcome measure, we did see a statistically significant and clinically meaningful treatment effect for elderly patients, and our safety results were consistent with previous studies in younger adults," Ochs-Ross said.
Follow-up Study Warranted
"These findings provide a strong rationale for a larger follow-up study to provide more evidence and further weigh the risks and benefits of this potentially promising addition as an augmentation agent to a limited geriatric TRD armamentarium," Bradley N. Gaynes, MD, professor of psychiatry, University of North Carolina School of Medicine, Chapel Hill, told Medscape Medical News.
"Treatment-resistant depression in the elderly is a key understudied area, and evidence-based interventions that are safe and effective are needed," Gaynes said.
The outcomes from this study are promising, "but are only starting to provide an evidence base for this population," he said.
Most important was that intranasal esketamine appeared relatively well-tolerated by the elderly sample, as no differences between the side effect profile in this older sample and that seen in a younger sample were noted.
"At the same time, it will be important to confirm that these same side effects are not more impairing for this geriatric population. Further, there were suggestions of benefit for this group. While the full age group of 65 and older did not demonstrate a statistically significant difference from the placebo group, the subset of [patients aged] 65 to 74 years did demonstrate a statistically and clinically meaningful difference," Gaynes said.
The study was sponsored by Janssen. Dr Ochs-Ross is an employee of Janssen Research and Development, LLC. Dr Gaynes has disclosed no relevant financial relationships.
American Society of Clinical Psychopharmacology (ASCP) 2018. Abstract W27, presented May 30, 2018.
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Cite this: Esketamine Nasal Spray Safe, Effective in Elderly Depression - Medscape - Jun 07, 2018.