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.
Alpha psychiatry – August 01, 2024
Source: PubMed
Summary
Scientists are exploring how blood-based biomarkers could predict who will respond best to esketamine, a breakthrough nasal spray treatment for major depressive disorder. Using metabolomics (study of small molecules in blood), researchers are tracking metabolic changes in 60 patients receiving esketamine treatment. This could lead to personalized depression care by identifying biological signatures that indicate likely treatment success.
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.