Open AccessManaging Esketamine Treatment Frequency Toward Successful Outcomes: Analysis of Phase 3 Data
Author(s) -
Michel Nijs,
Ewa Wajs,
Leah Aluisio,
Ibrahim Turkoz,
Ella Daly,
Adam Janik,
Stephane Borentain,
Jaskaran Singh,
Allitia DiBernardo,
Frank Wiegand
Publication year - 2020
Publication title -
international journal of neuropsychopharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.897
H-Index - 107
eISSN - 1469-5111
pISSN - 1461-1457
DOI - 10.1093/ijnp/pyaa027
Subject(s) - medicine , treatment resistant depression , depression (economics) , rating scale , clinical global impression , ketamine , post hoc analysis , anesthesia , antidepressant , psychology , placebo , developmental psychology , alternative medicine , pathology , hippocampus , economics , macroeconomics
Background Esketamine nasal spray was recently approved for treatment-resistant depression. The current analysis evaluated the impact of symptom-based treatment frequency changes during esketamine treatment on clinical outcomes. Methods This is a post-hoc analysis of an open-label, long-term (up to 1 year) study of esketamine in patients with treatment-resistant depression (SUSTAIN 2). During a 4-week induction phase, 778 patients self-administered esketamine twice weekly plus a new oral antidepressant daily. In responders (≥50% reduction in Montgomery-Åsberg Depression Rating Scale total score from baseline), esketamine treatment frequency was thereafter decreased during an optimization/maintenance phase to weekly for 4 weeks and then adjusted to the lowest frequency (weekly or every other week) that maintained remission (Montgomery-Åsberg Depression Rating Scale ≤ 12) based on a study-defined algorithm. The relationship between treatment frequency and symptom response, based on clinically meaningful change in Clinical Global Impression–Severity score, was subsequently evaluated 4 weeks after treatment frequency adjustments in the optimization/maintenance phase. Results Among 580 responders treated with weekly esketamine for the first 4 weeks in the optimization/maintenance phase (per protocol), 26% continued to improve, 50% maintained clinical benefit, and 24% worsened. Thereafter, when treatment frequency could be reduced from weekly to every other week, 19% further improved, 49% maintained benefit, and 32% worsened. For patients no longer in remission after treatment frequency reduction, an increase (every other week to weekly) resulted in 47% improved, 43% remained unchanged, and 10% worsened. Conclusions These findings support individualization of esketamine nasal spray treatment frequency to optimize treatment response in real-world clinical practice. Trial Registration ClinicalTrials.gov identifier: NCT02497287