Predictors and process moderators of EMDR therapy for depressive symptoms: Protocol for a series of observational N-of-1 trials

This study aims to present a protocol for evaluating factors associated with EMDR therapy effectiveness for depressive symptoms in real-world clinical settings.

Article Abstract

“Background: Eye Movement Desensitization and Reprocessing (EMDR) therapy is an evidence-based intervention for trauma-related disorders and other psychological conditions, including depression. Although the positive effects of EMDR in treating depressive symptoms have been empirically supported under controlled conditions, little is known about individual and process-related factors associated with treatment outcome for depression.

Objective: This study aims to present a protocol for evaluating factors associated with EMDR therapy effectiveness for depressive symptoms in real-world clinical settings. The primary objective is to identify individual characteristics that may predict treatment response. Secondly, we aim to examine potential moderating factors of EMDR for depressive symptoms, including psychologically associated symptoms and therapeutic relationship.

Methods: A prospective observational design that combines a series of N-of-1 trials will be conducted in thirty-two patients presenting with clinically significant levels of anxiety, depressive, dissociative, or post-traumatic stress symptoms in at least one domain. Italian EMDR therapists voluntarily participate in the study and enroll one patient each who meets the inclusion criteria. Data will be collected via REDCap at different timepoints, from baseline to the end of therapy. A Bayesian multilevel random-effects meta-analysis and meta-regression will be conducted. This design allows for analysis of model parameters to generate direct probabilistic statements about scientific hypotheses, extending beyond treatment efficacy.

Conclusion: Results will provide insights into factors influencing the effectiveness of EMDR therapy for depressive symptoms. The understanding of predictors and process moderators is expected to improve clinical interventions and contribute to bridging the current gap between research and clinical practice. Findings are expected to contribute to a promising line of research aimed to advance clinical practice through the systematic collection of real-world data. Moreover, the results may strengthen the evidence on EMDR therapy in real-world settings, and support the optimization of treatment based on individual patient characteristics.

Clinical trial registration: ClinicalTrials.gov, identifier NCT07033741.”

—Description from publisher

Article Access

Open Access 

Cotardo, F., Koumantakis, E., Rossini, P. G., Malandrone, F., Berchialla, P., Ostacoli, L., & Carletto, S. (2026). Predictors and process moderators of EMDR therapy for depressive symptoms: Protocol for a series of observational N-of-1 trials. Frontiers in Psychology, 16:16188526. Open access: https://doi.org/10.3389/fpsyg.2025.1688526