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, Daniele Cavaleri, Ilaria Riboldi, Cristina Crocamo, Renato de Filippis, Riccardo Zandonella Callegher, Giuseppe Paglia, Umberto Albert, Pasquale De Fazio, Giuseppe Carrà
Alpha psychiatry August 1, 2024 DOI: 10.5152/alphapsychiatry.2024.241549 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational prospective study protocol Peer reviewed |
|---|---|
| Sample size | 60 |
| Population | People with treatment-resistant depression from 3 clinical sites in Italy |
| Intervention | Esketamine nasal spray |
| Duration | 4-week induction phase (twice a week) plus 4-week maintenance phase (once a week), with endpoints at weeks 4 and 8 |
| Topics | Depression Esketamine |
| Keywords | Biomarkers biological markers Molecular markers Biochemical markers Clinical depression Individualized medicine Metabolomics metabolic profiling Metabolite analysis |
| Citations | 4 |
| Key findings | The protocol aims to identify metabolic biosignatures that may represent novel correlates of response to esketamine treatment in treatment-resistant depression. |
Abstract
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. This is the protocol of an observational, prospective study. 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. An involvement of energy metabolism, amino acid metabolism, urea cycle, and nitric oxide synthesis in response to treatment with esketamine nasal spray is hypothesized. 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.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.