EEG-based Neurofeedback to Improve Emotion Regulation in Major Depressive Disorder: A Randomized Clinical Trial
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-65
SponsorCorporacion Parc Tauli
About this trial
The goal of this clinical trial is to evaluate whether EEG-based neurofeedback targeting the emotion regulation network through swLORETA can improve emotional regulation and reduce symptoms in adults with Major Depressive Disorder (MDD) who have not responded sufficiently to first-line treatments. The main questions it aims to answer are:
* Does EEG-neurofeedback improve emotional self-regulation and reduce clinical symptoms in patients with MDD with or without anxiety symptoms? * Are changes in EEG resting-state activity and stress biomarkers (e.g., cortisol) associated with clinical improvement?
Researchers will compare an active neurofeedback group, a sham (placebo) neurofeedback group, and a treatment-as-usual control group to see if real-time EEG-neurofeedback leads to greater improvement in mood, emotional regulation, and neurophysiological indicators than placebo or no additional intervention.
Participants will:
* Receive 10 sessions of either real or sham EEG-neurofeedback (or no sessions in the control group) over 5 weeks. * Complete clinical, psychological, and neurophysiological assessments before (week 0) and after the intervention (week 6). * Provide repeated saliva samples to assess stress-related biomarkers at week 0 and week 6. * Continue their standard pharmacological treatment throughout the study.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
A primary diagnosis of Major Depressive Disorder (MDD), established by qualified psychiatrists according to DSM-5 criteria.
Patients with comorbid anxiety or anxiety symptoms will be included, provided that MDD is the primary diagnosis.
Participants must score at least 20 on the Montgomery-Åsberg Depression Rating Scale (MADRS), indicating a moderate level of depression.
All participants must be on a stable psychopharmacological treatment for at least 6 weeks before beginning of the study.
Disqualifiers
Patients with a concurrent diagnosis of MDD and other severe psychiatric disorders.
Patients with serious physical illnesses that could interfere with study participation or the interpretation of results.
Participants currently undergoing structured psychotherapy or other interventions unrelated to standard psychopharmacological treatment.
Patients presenting with active suicidal ideation, as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS), at the time of screening will not be eligible due to associated risks.
Trial design
Design model
Parallel
Treatments tested in this trial
Active swLORETA Z-score Neurofeedback
DeviceParticipants receive 10 sessions (25 minutes each, twice per week for 5 weeks) of EEG-based neurofeedback using the NeuroGuide® software and a 24-channel EEG recording system (eego™, ANT Neuro). The neurofeedback protocol is based on real-time swLORETA Z-score training targeting brain regions involved in emotion regulation. Feedback is provided via gamified visual displays when EEG activity moves toward normative patterns. This is an operant conditioning-based protocol designed to enhance emotional self-regulation.
Yoked-sham swLORETA Z-score Neurofeedback
DeviceParticipants receive 10 sessions identical in appearance and duration to the active neurofeedback condition. However, the feedback provided is not based on their own EEG activity. Instead, it is pre-recorded data from a matched participant in the active group ("yoked" design), ensuring no real-time neurophysiological modulation occurs. The same EEG equipment and visual feedback interface are used to maintain blinding.
Treatment groups
72 Participants
are divided into 3 treatment groupsGroup A: Active Neurofeedback (EEG-NF)Experimental treatment 1 intervention
Group B: Yoked-sham NeurofeedbackSham comparator 1 intervention
Group C: Treatment as Usual (Control)No intervention 0 interventions
Trial outcomes
Primary outcomes
1
Change in depressive symptom severity, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), from baseline to post-intervention.
The MADRS is a validated clinician-administered scale widely used to assess the severity of depressive symptoms. A clinically significant response is defined as a reduction of more than 50% from the baseline score. Clinical remission is defined as a final score of 10 or below. The Spanish version of the MADRS, validated for use in the study population, will be administered by trained clinicians at three time points: baseline (pre-intervention), mid-treatment (after session 5), and post-intervention (after session 10).
Time frame
From enrollment (week 0) to the end of treatment (week 6)2
Change in depressive symptoms measured by the Hamilton Depression Rating Scale (HAM-D), from baseline to post-treatment
The HAM-D is a clinician-administered scale that evaluates a broad range of depressive symptoms, including insomnia, anxiety, and somatic complaints. It complements the MADRS by covering additional symptom domains and will be administered at baseline and post-treatment to assess clinical change.
Time frame
From enrollment (week 0) to the end of treatment (week 6)3
Change in self-reported anxiety symptoms measured by the Beck Anxiety Inventory (BAI), from baseline to post-intervention
The BAI is a 21-item self-report instrument designed to assess the severity of anxiety symptoms. It will be used to evaluate the potential impact of the neurofeedback intervention on co-occurring anxiety.
Time frame
From enrollment (week 0) to the end of treatment (week 6)4
Change in self-reported depressive symptoms measured by the Beck Depression Inventory-II (BDI-II), from baseline to post-intervention
The BDI-II is a widely used self-report questionnaire designed to assess the presence and severity of depressive symptoms.It will be administered at baseline and post-treatment to complement clinician-rated measures and capture subjective aspects of depression, such as patient-reported changes in mood, cognition, and physical symptoms related to depression.
Time frame
From enrollment (week 0) to the end of treatment (week 6)Secondary outcomes
1
Change in sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI)
The PSQI is a self-report instrument that evaluates subjective sleep quality and disturbances. It will assess whether neurofeedback improves sleep patterns often disrupted in MDD.
Time frame
Baseline (Week 0), Post-treatment (Week 6)2
Change in rumination measured by the Ruminative Responses Scale (RRS)
The RRS assesses the frequency of ruminative thoughts and responses to depressed mood. It will evaluate the impact of neurofeedback on cognitive vulnerability to depression and anxiety.
Time frame
Baseline (Week 0), Post-treatment (Week 6)3
Change in sensitivity to punishment and reward measured by the SPSRQ
The Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ) assesses behavioral inhibition and activation. It will explore changes in emotional responsiveness and motivational systems.
Time frame
Baseline (Week 0), Post-treatment (Week 6)Sponsors and contacts
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Corporacion Parc Tauli
Lead sponsor
Horizon 2020 - European Commission
Collaborator
Source ClinicalTrials.gov