A Meta-Analysis of the Antidepressant Responses in Pivotal Trials on Esketamine Nasal Spray and Atypical Antipsychotics

Lien Wang,1,2 Xiaowei Chen,1 Xiaojing Gu,1 Heidi De Smedt,3 Vanina Popova,3 Dong-Jing Fu,4 Carla M Canuso,4 Wayne C Drevets,2 Guang Chen2 1Janssen Research & Development, LLC, Janssen Pharmaceutical Companies of Johnson & Johnson, Shanghai, People’s Republic of China; 2Janssen Research & Development, LLC, Janssen Pharmaceutical Companies of Johnson & Johnson, Brisbane, CA, USA; 3Janssen Research & Development, LLC, Janssen Pharmaceutical Companies of Johnson & Johnson, Beerse, Belgium; 4Janssen Research & Development, LLC, Janssen Pharmaceutical Companies of Johnson & Johnson, Raritan, NJ, USACorrespondence: Guang Chen, Janssen Fellow, Scientific Director, Translational Research, Mood DAS, Neuroscience Therapeutic Area, Janssen R & D, LLC, Janssen Pharmaceutical Companies of Johnson and Johnson, 3210 Merryfield Row, Room 1908, San Diego, CA, 92121, USA, Tel +1 (240) 602 7950, Email guangchenmd@gmail.comPurpose: This meta-analysis assessed whether atypical antipsychotics (AAPs) and esketamine nasal spray (ESK-NS), which are mechanistically distinct, differ in antidepressant outcomes.Patients and Methods: Data were extracted from 12 trials of ESK-NS or AAPs in depressed patients (4276) with inadequate response or resistance to conventional antidepressants. Montgomery-Åsberg Depression Rating Scale (MADRS) score reductions from baseline and response rates (≥ 50% reduction) were analyzed.Results: At endpoint, the estimated MADRS score reduction of pooled ESK-NS arms was greater than pooled AAP arms (+9.16 points, p < 0.0001). The reduction also was greater in the pooled control arms of the ESK-NS trials than the pooled control arms of the AAP trials (+7.57 points, p < 0.0001). The mean difference in the reductions between pooled ESK-NS and control arms was 1.87 points greater than that between pooled AAP and control arms, but this difference was not significant (95% CI: − 4.49, 0.74, p = 0.16). Relative to their respectiv