Flexible Dosing of Esketamine Nasal Spray Effective Over Long-Term
An analysis of patients in a long-term extension study of flexibly dosed esketamine nasal spray, in combination with an oral antidepressant, found durable long-term efficacy and safety of the treatment whether dosed weekly, every other week, or every 4 weeks, according to a poster presented at the 2024 NEI Fall Congress.
“Flexible dosing of esketamine nasal spray, adjusted according to disease severity, is effective at maintaining long-term clinical stability in patients with treatment-resistant depression,” reported first author John Zajecka, MD, of Rush University Medical Center, Chicago, Illinois, and coauthors of the abstract.
SUSTAIN-3 is an open-label, phase 3 long-term extension study of individualized, flexibly dosed esketamine in conjunction with an oral antidepressant in patients with treatment-resistant depression. The analysis included a total 1097 adult patients. Among them, 591 had a dosing frequency of weekly, 369 had a dosing frequency of every other week, and 137 had a dosing frequency of every 4 weeks during the optimization/management phase.
The mean duration of esketamine treatment was 42.9 months for patients dosed weekly, 46.5 months for patients dosed every other week, and 46.4 months for patients dosed every 4 weeks. The median mode dose of esketamine received per treatment was 84 mg with weekly and every-other-week dosing and 56 mg for every-4-weeks dosing.
For all dosing frequency subgroups, mean total scores on the Montgomery–Åsberg Depression Rating Scale (MADRS) and 9-item Patient Health Questionnaire (PHQ-9) remained stable over time, according to the poster.
The mean change on MADRS total scores from the optimization/management phase baseline to the end of the study, a span of 312 weeks based on last-observation-carried-forward data, was 2.0 with weekly, −1.8 with every-other-week, and −2.2 for every-4-week dosing. The mean change on PHQ-9 total score was 1.5 with weekly, −0.3 with every-other-week, and −0.8 with every-4-weeks dosing.
At the end of the optimization/management phase, the proportion of patients in remission, defined as a MADRS total score of 12 or less, was 24.7% with weekly, 75.6%, with every-other-week, and 88.3% with every-4-weeks dosing, researchers reported.
“Achieving full response and ultimately remission is among the greatest unmet needs in treatment of resistant depressed patients, said Dr Zajecka in email correspondence with Psychiatry and Behavioral Health Learning Network.
“This study demonstrated the potential positive impact in some patients using flexible dose frequency over extended time to achieve and sustain optimal outcomes. The durability of high remission rates reported in this study is also noteworthy as it continues to underscore the importance of tailoring treatment approaches to achieve optimal and stable outcomes.”
Treatment-emergent adverse events were consistent with the established esketamine safety profile.
The poster was supported by Janssen Scientific Affairs, a Johnson & Johnson company.
Reference
Zajecka J, Fu D, Zaki N, et al. Long-term safety and efficacy of esketamine nasal spray by dosing frequency in adults with treatment-resistant depression: analysis of the SUSTAIN-3 study. Poster presented at NEI Congress; November 7-10, 2024; Colorado Springs, Colorado.
