Real-world experience of esketamine use to manage treatment-resistant depression: A multicentric study on safety and effectiveness (REAL-ESK study).

Background: Treatment-resistant Depression (TRD) represents a widespread disorder with significant direct and indirect healthcare costs. esketamine, the S-enantiomer of ketamine, has been recently approved for TRD, but real-world studies are needed to prove its efficacy in naturalistic settings.
Objectives: Evaluate the effectiveness and safety of esketamine nasal spray in a clinical sample of patients with TRD from several Italian mental health services.
Methods: REAL-ESK study is an observational, retrospective and multicentric study comprising a total of 116 TRD patients treated with esketamine nasal spray. Anamnestic data and psychometric assessment (MADRS, HAMD-21, HAM-A) were collected from medical records at baseline (T0), one month (T1) and three month (T2) follow-ups.
Results: A significant reduction of depressive symptoms was found at T1 and T2 compared to T0. A dramatic increase in clinical response (64.2 %) and remission rates (40.6 %) was detected at T2 compared to T1. No unexpected safety concerns were observed, side effects rates were comparable to those reported in RCTs. No differences in efficacy have been found among patients with and without psychiatric comorbidities.
Limitations: The open design of the study and the absence of a placebo or active comparator group are limitations. The study lacks an inter-rater reliability evaluation of the assessments among the different centres. Side effects evaluation did not involve any specific scale.
Conclusions: Our findings support the safety and tolerability of esketamine in a real-world TRD sample. The later response and the non-inferiority in effectiveness in patients with comorbidities represent novel and interesting findings.
Competing Interests: Conflict of interest Giovanni Martinotti has been a consultant and/or a speaker and/or has received research grants from Angelini, Doc Generici, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Servier and Recordati. Alessandro Bertolino and Ileana Andriola were both speakers at Jannssen-sponsored conference. Andrea Fagiolini has been a consultant and/or a speaker and/or has received research grants from Allergan, Angelini, Apsen, Boehringer Ingelheim, Doc Generici, FB-Health, Italfarmaco, Janssen, Lundbeck, Mylan, Otsuka, Pfizer, Recordati, Sanofi Aventis, Sunovion, Vifor. Bernardo Dell'Osso has received lecture honoraria from Angelini, Lundbeck, Janssen, Pfizer, Neuraxpharm, Arcapharma, and Livanova. Massimo di Giannantonio has been a consultant and/or a speaker and/or has received research grants from Angelini, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Servier, Recordati. Antonio Vita received grant/research support and speaker/consultant fees for Angelini, Boheringer Ingelheim, Innovapharma, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Recordati, Roche, Rovi Pharma, Takeda. Giuseppe Maina has been a consultant/speaker for Angelini, Boheringer, Fb Health, Innovapharma, Italfarmaco, Janssen, Otsuka, Lundbeck, Sanofi. Gabriele Sani has been a consultant/speaker for Angelini, Fb Health, Italfarmaco, Janssen, Otsuka, Lundbeck, Sanofi. Roger McIntyre has received grant/research support from CIHR/GACD/Chinese National Natural Research Foundation and speaking or consultation fees from AbbVie, Bausch Health, Eisai, Intra-Cellular, Janssen, Kris, Lundbeck, Minerva, Neurocrine, Novo Nordisk, Eli Lilly, Otsuka, Pfizer, Purdue, Sunovion, and Takeda; he is also the CEO of Champignon Brands, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.