Affiliations 

  • 1 Director Neuroscience R&D, Janssen Research & Development BE, Turnhoutseweg 30, 2340 Beerse, Belgium. ewajs@its.jnj.com
  • 2 Janssen Research & Development, San Diego, California, USA
  • 3 Janssen Inc, Toronto, Ontario, Canada
  • 4 Janssen Research & Development, Titusville, New Jersey, USA
  • 5 Janssen Research & Development, Pennington, New Jersey, USA
  • 6 The Yale Depression Research Program, Yale University, New Haven, Connecticut, USA
  • 7 Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London & South London, London, United Kingdom
  • 8 Department of Psychiatry and Psychotherapy, Medical University, Vienna, Austria
  • 9 Department of Psychological Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 10 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine and Institute of Brain Science, National Yang-Ming University, Taiwan
  • 11 Department of Psychiatry/Kyung Hee University College of Medicine, Seoul, South Korea
  • 12 Peninsula Therapeutic and Research Group, Frankston, Victoria, Australia
  • 13 Department of Psychiatry, Depression Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
J Clin Psychiatry, 2020 04 28;81(3).
PMID: 32316080 DOI: 10.4088/JCP.19m12891

Abstract

OBJECTIVE: To evaluate long-term safety and efficacy of esketamine nasal spray plus a new oral antidepressant (OAD) in patients with treatment-resistant depression (TRD).

METHODS: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse to ≥ 2 OAD treatments) were enrolled directly or transferred from a short-term study (patients aged ≥ 65 years). Esketamine nasal spray (28-mg, 56-mg, or 84-mg) plus new OAD was administered twice a week in a 4-week induction (IND) phase and weekly or every-other-week for patients who were responders and entered a 48-week optimization/maintenance (OP/MAINT) phase.

RESULTS: Of 802 enrolled patients, 86.2% were direct-entry and 13.8% were transferred-entry; 580 (74.5%) of 779 patients who entered the IND phase completed the phase, and 150 (24.9%) of 603 who entered the OP/MAINT phase completed the phase. Common treatment-emergent adverse events (TEAEs) were dizziness (32.9%), dissociation (27.6%), nausea (25.1%), and headache (24.9%). Seventy-six patients (9.5%) discontinued esketamine due to TEAEs. Fifty-five patients (6.9%) experienced serious TEAEs. Most TEAEs occurred on dosing days, were mild or moderate in severity, and resolved on the same day. Two deaths were reported; neither was considered related to esketamine. Cognitive performance generally either improved or remained stable postbaseline. There was no case of interstitial cystitis or respiratory depression. Treatment-emergent dissociative symptoms were transient and generally resolved within 1.5 hours postdose. Montgomery-Åsberg Depression Rating Scale total score decreased during the IND phase, and this reduction persisted during the OP/MAINT phase (mean [SD] change from baseline of respective phase to endpoint: IND, -16.4 [8.76]; OP/MAINT, 0.3 [8.12]).

CONCLUSIONS: Long-term esketamine nasal spray plus new OAD therapy had a manageable safety profile, and improvements in depression appeared to be sustained in patients with TRD.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02497287.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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