Rachel Ochs-Ross1, Ella J Daly2, Yun Zhang3, Rosanne Lane2, Pilar Lim2, Randall L Morrison2, David Hough2, Husseini Manji2, Wayne C Drevets4, Gerard Sanacora5, David C Steffens6, Caleb Adler7, Rupert McShane8, Raphaël Gaillard9, Samuel T Wilkinson5, Jaskaran B Singh4. 1. Janssen Research & Development, LLC (RO-R, EJD, RL, PL, RLM, DH, HM), Titusville, NJ. Electronic address: rochsro@its.jnj.com. 2. Janssen Research & Development, LLC (RO-R, EJD, RL, PL, RLM, DH, HM), Titusville, NJ. 3. Janssen Research & Development, LLC (YZ), Fremont, CA. 4. Janssen Research & Development, LLC (WCD, JBS), San Diego, CA. 5. Yale University School of Medicine (GS, STW), New Haven, CT. 6. University of Connecticut School of Medicine (DCS), Farmington, CT. 7. University of Cincinnati College of Medicine (CA), Cincinnati, OH. 8. University of Oxford (RM), Oxford, United Kingdom. 9. Hôpital Sainte Anne (RG), Paris, France.
Abstract
BACKGROUND:Elderly patients with major depression have a poorer prognosis, are less responsive to treatment, and show greater functional decline compared with younger patients, highlighting the need for effective treatment. METHODS: This phase 3 double-blind study randomized patients with treatment-resistant depression (TRD) ≥65 years (1:1) to flexibly dosed esketamine nasal spray and new oral antidepressant (esketamine/antidepressant) or new oral antidepressant and placebo nasal spray (antidepressant/placebo). The primary endpoint was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to day 28. Analyses included a preplanned analysis by age (65-74 versus ≥75 years) and post-hoc analyses including age at depression onset. RESULTS: For the primary endpoint, the median-unbiased estimate of the treatment difference (95% CI) was -3.6 (-7.20, 0.07); weighted combination test using MMRM analyses z = 1.89, two-sided p = 0.059. Adjusted mean (95% CI) difference for change in MADRS score between treatment groups was -4.9 (-8.96, -0.89; t = -2.4, df = 127; two-sided nominal p = 0.017) for patients 65 to 74 years versus -0.4 (-10.38, 9.50; t = -0.09, two-sided nominal p = 0.930) for those ≥75 years, and -6.1 (-10.33, -1.81; t = -2.8, df = 127; two-sided nominal p = 0.006) for patients with depression onset <55 years and 3.1 (-4.51, 10.80; t = 0.8, two-sided nominal p = 0.407) for those ≥55 years. Patients who rolled over into the long-term open-label study showed continued improvement with esketamine following 4 additional treatment weeks. CONCLUSIONS: Esketamine/antidepressant did not achieve statistical significance for the primary endpoint. Greater differences between treatment arms were seen for younger patients (65-74 years) and patients with earlier onset of depression (<55 years).
RCT Entities:
BACKGROUND: Elderly patients with major depression have a poorer prognosis, are less responsive to treatment, and show greater functional decline compared with younger patients, highlighting the need for effective treatment. METHODS: This phase 3 double-blind study randomized patients with treatment-resistant depression (TRD) ≥65 years (1:1) to flexibly dosed esketamine nasal spray and new oral antidepressant (esketamine/antidepressant) or new oral antidepressant and placebo nasal spray (antidepressant/placebo). The primary endpoint was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to day 28. Analyses included a preplanned analysis by age (65-74 versus ≥75 years) and post-hoc analyses including age at depression onset. RESULTS: For the primary endpoint, the median-unbiased estimate of the treatment difference (95% CI) was -3.6 (-7.20, 0.07); weighted combination test using MMRM analyses z = 1.89, two-sided p = 0.059. Adjusted mean (95% CI) difference for change in MADRS score between treatment groups was -4.9 (-8.96, -0.89; t = -2.4, df = 127; two-sided nominal p = 0.017) for patients 65 to 74 years versus -0.4 (-10.38, 9.50; t = -0.09, two-sided nominal p = 0.930) for those ≥75 years, and -6.1 (-10.33, -1.81; t = -2.8, df = 127; two-sided nominal p = 0.006) for patients with depression onset <55 years and 3.1 (-4.51, 10.80; t = 0.8, two-sided nominal p = 0.407) for those ≥55 years. Patients who rolled over into the long-term open-label study showed continued improvement with esketamine following 4 additional treatment weeks. CONCLUSIONS:Esketamine/antidepressant did not achieve statistical significance for the primary endpoint. Greater differences between treatment arms were seen for younger patients (65-74 years) and patients with earlier onset of depression (<55 years).
Authors: Ashley A Conley; Amber E Q Norwood; Thomas C Hatvany; James D Griffith; Kathryn E Barber Journal: Psychopharmacology (Berl) Date: 2021-03-31 Impact factor: 4.530
Authors: Steven Pennybaker; Brian J Roach; Susanna L Fryer; Anusha Badathala; Art W Wallace; Daniel H Mathalon; Tobias F Marton Journal: Psychopharmacology (Berl) Date: 2021-08-07 Impact factor: 4.530