Exploratory Deep Phenotyping of Early Antidepressant Treatment Effects in a Longitudinal, Double-Blind, Randomized, Controlled, Parallel-Group Pre-Post Design - a Study Protocol from Research Consortium OptiMD

BackgroundA better understanding of neurobiological mechanisms behind clinical depression and optimization of pharmacological treatment options remain enormous challenges. Early subtyping of depression might be achieved by discovering reliable trait markers or by early detection of changes in potential state markers, for example during the first days of antidepressant treatment. ObjectiveThe primary objective of this trial was to explore early neurobiological dynamics during the first week of antidepressant treatment within the same drug-naive inpatients in a large deep-phenotyping exploration applying various measurement modalities as described below. MethodsA longitudinal deep-phenotyping experimental design involved holistic measurements of various markers with state-of-the art technology over five axes of investigation: MR neuroimaging, dexamethasone/CRH-testing, gut microbiome composition, inflammatory proteome and lipidomics. Therapy during these measurements was controlled and standardized by conducting a double-blind, randomized parallel group design with four balanced arms during the first seven days of medication that encompassed three common first-line, yet pharmacologically distinguishable, antidepressants (escitalopram, mirtazapine, agomelatine) or placebo. The complete trial period has been 60 days including a third major longitudinal point of investigation at the end of trial. An additional control cohort with matched healthy volunteers was participating in the same set of investigations as patients at baseline, except dexamethasone/CRH-testing. Trial statusThis trial has extensively served two subprojects of the German National Research Consortium OptiMD. It has been registered at the European Clinical Trials Register with identifier 2013-003370-27 and was initiated in January 2016. Recruitment of 70 inpatients and 25 healthy participants has been completed in August 2021 without any known harms in regard to study participation. Collection of data is still ongoing and hence, databases are not yet closed. Analyses of first complete datasets have begun and we hope that our deep-phenotyping exploration might contribute to new perspectives on clinical depression and its treatment. Protocol outline O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=155 SRC="FIGDIR/small/25341376v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@cdba53org.highwire.dtl.DTLVardef@83de21org.highwire.dtl.DTLVardef@16c75edorg.highwire.dtl.DTLVardef@1b2380e_HPS_FORMAT_FIGEXP M_FIG C_FIG