Efficacy

Efficacy Data

See how SPRAVATO™ plus an oral AD performed in short- and long-term studies

Superior improvement in depression symptoms vs oral antidepressant (AD) plus placebo at Week 41,2

MADRS=Montgomery-Åsberg Depression Rating Scale.

Primary Endpoint

  • Change from baseline (Day 1) to endpoint (Day 28) in Montgomery-Åsberg Depression Rating Scale (MADRS) score

Flexible Dosing

  • Patients (aged 18-64 years) were randomized to receive treatment with SPRAVATO™ 56 mg or 84 mg plus a newly initiated oral AD or a newly initiated oral AD plus placebo nasal spray on Day 1
  • Dosages could be titrated to 84 mg or maintained on 56 mg, and were adjusted on Day 4, 8, 11, or 15. Dosages remained stable after Day 15

Oral Antidepressant

  • A newly initiated open-label oral AD (SSRIs: escitalopram, sertraline; SNRIs: duloxetine, venlafaxine extended-release) was initiated on Day 1
  • The selection of the newly initiated oral AD was determined by the investigator based on patient’s prior history

*Optional taper of up to 3 weeks.

SPRAVATO™ plus an oral AD significantly delayed time to relapse in a long-term maintenance trial1,3*

After an initial 16 weeks of treatment with SPRAVATO™, patients in stable remission and stable response entered the maintenance phase, and were separately randomized.

Stable remission was defined as a MADRS total score of ≤12 in at least 3 of the last 4 weeks of the optimization phase

Stable response was defined as a MADRS total score reduction ≥50% from baseline in each of the last 2 weeks of the optimization phase but does not meet criteria for stable remission

*Relapse was defined as a MADRS total score of ≥22 for 2 consecutive assessments separated by 5 to 15 days and/or hospitalization for worsening depression, or any other clinically relevant event determined per clinical judgment to be suggestive of a relapse of depressive illness.

Primary Endpoint

  • Time to relapse (cumulative distribution) during the maintenance phase among stable remitters
    • Relapse was defined as one of the following:
      • MADRS total score of ≥22 for 2 consecutive assessments separated by 5 to 15 days
      • Hospitalization for worsening depression, or any other clinically relevant event determined per clinical judgment to be suggestive of a relapse of depressive illness

Enrollment

  • 437 patients (aged 18-64 years) were directly enrolled
    • Patients who were directly enrolled received SPRAVATO™ (56 mg or 84 mg twice/week) plus a new oral AD in a 4-week open-label induction phase before entering a 12-week optimization phase
  • 268 patients (aged 18-64 years) were transferred from short-term studies

*Stable remission was defined as a MADRS total score of ≤12 in at least 3 of the last 4 weeks of the optimization phase.

Stable response was defined as a MADRS total score reduction ≥50% from baseline in each of the last 2 weeks of the optimization phase but does not meet criteria for stable remission.

References

1. SPRAVATO™ [Prescribing Information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. March 2019.

2. Popova V, Daly EJ, Trivedi M, et al. Randomized, double-blind study of flexibly-dosed intranasal esketamine plus oral antidepressant vs. active control in treatment-resistant depression. Presented at: 2018 Annual Meeting of the American Society of Clinical Psychopharmacology (ASCP); May 29-June 1, 2018; Miami, FL. 

3. Daly EJ, et al. A randomized withdrawal, double-blind, multicenter study of esketamine nasal spray plus an oral antidepressant for relapse prevention in treatment-resistant depression. Presented at: 2018 Annual Meeting of the American Society of Clinical Psychopharmacology (ASCP); May 30, 2018; Miami, FL.