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

This first open-label real-world study (n=116) of esketamine (Spravato, up to 84mg, multiple dosings) finds similar positive outcomes as previous clinical trials. At three months, the response rate (64%) and remission (41%) for those with treatment-resistant depression are impressive. Only 3% of participants dropped out of the study because of side effects.

Abstract

“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 First, 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.”

Authors: Giovanni Martinotti, Antonio Vita, Andrea Fagiolini, Giuseppe Maina, Alessandro Bertolino, Bernardo Dell’Osso, Alberto Siracusano, Massimo Clericij, Antonello Bellomo, Gabriele Sanil, Giacomo d’Andrea, Roberto D. Chiaie, Andreas Conca, Stefano Barlati, Giorgio Di Lorenzo, Pasquale De Fazio, Sergio De Filippis, Giuseppe Nicolò, Gianluca Rosso, Alessandro Valchera, Domenica Nucifora, Stefania Di Mauro, Roberta Bassetti, Vassilis Martiadis, Miriam Olivola, Sandro Belletti, Ileana Andriola, Marco Di Nicola, Mauro Pettorruso, Roger S. McIntyre & Massimodi Giannantonio