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. 2024 Aug 1;25(4):555-560.
doi: 10.5152/alphapsychiatry.2024.241549. eCollection 2024 Aug.

The Resistant Depression Response to Esketamine Assessing Metabolomics (ReDREAM) Project-Untargeted Metabolomics to Identify Biomarkers of Treatment Response to Intranasal Esketamine in Individuals with Treatment-Resistant Depression: A Study Protocol

Francesco Bartoli  1 , Daniele Cavaleri  1 , Ilaria Riboldi  1 , Cristina Crocamo  1 , Renato de Filippis  2 , Riccardo Zandonella Callegher  3 , Giuseppe Paglia  1 , Umberto Albert  3 , Pasquale De Fazio  2 , Giuseppe Carrà  1
Affiliations

The Resistant Depression Response to Esketamine Assessing Metabolomics (ReDREAM) Project-Untargeted Metabolomics to Identify Biomarkers of Treatment Response to Intranasal Esketamine in Individuals with Treatment-Resistant Depression: A Study Protocol

Francesco Bartoli et al. Alpha Psychiatry. .

Abstract

Objective: Treatment-resistant depression (TRD) affects around 20-30% of people with major depressive disorder. In 2019, esketamine nasal spray was approved for TRD by both the US Food and Drug Administration and the European Medicines Agency. While its clinical efficacy and safety are proven, the mechanisms underlying its antidepressant effect remain unclear. The use of metabolomics may allow understanding the metabolic effects of esketamine and predicting biological features associated with clinical response in TRD. Nonetheless, there is a lack of studies exploring the predictive value of metabolomics. The Resistant Depression Response to Esketamine Assessing Metabolomics (ReDREAM) project aims at identifying metabolic biosignatures that may represent novel correlates of response to esketamine treatment.

Study design: This is the protocol of an observational, prospective study.

Methods: We plan to select 60 people with TRD from 3 clinical sites in Italy. The participants will be administered with esketamine nasal spray, following standard clinical practice, twice a week for 4 weeks ("induction phase"), then once a week for 4 additional weeks ("maintenance phase"). We will test the correlations between baseline metabolic profile and depressive symptom improvement at study endpoints (weeks 4 and 8) and we will explore the likelihood of different metabolic phenotypes between responders and non-responders.

Expected results: An involvement of energy metabolism, amino acid metabolism, urea cycle, and nitric oxide synthesis in response to treatment with esketamine nasal spray is hypothesized.

Conclusion: Unbiased data from untargeted metabolomics associated with clinical changes after esketamine treatment may contribute to define new paradigms for precision psychiatry-oriented, personalized care of TRD.

Keywords: Biomarkers; esketamine; major depressive disorder; metabolomics.

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Conflict of interest statement

Declaration of Interests: Francesco Bartoli is Editor-in-Chief of Alpha Psychiatry and was not involved in the processing of this article. In the last three years, he has received consultant fees by IQVIA Solutions Italy and Edra S.p.A., and carried out paid editorial activities for Elsevier and AVES. In the last three years Renato de Filippis has received speaker fee from Janssen, Angelini, Lundbeck, and Rovi, and travel support from Rovi, Otsuka, Lundbeck, and Janssen. In the last three years Umberto Albert received speaker fee from Angelini Pharma, Janssen Pharmaceutica, OM Pharma Suisse, Lundbeck, Fidia, and Boehringer. The other authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
Flow diagram of study procedures and assessment schedule.
See this image and copyright information in PMC

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