Trial results for a study investigating external Combined Occipital and Trigeminal Neurostimulation (eCOT-NS) for Major Depressive Disorder (MDD) were posted on ClinicalTrials.gov on 2025-08-12, with 124 participants enrolled.
Background
Major Depressive Disorder (MDD) is a common and serious mental health condition characterized by persistent sadness and loss of interest, significantly impacting daily life. Current treatments include psychotherapy, pharmacotherapy, and various neuromodulation techniques. However, many patients do not achieve full remission or experience side effects, highlighting the need for alternative or adjunctive therapies. Non-invasive approaches like neurostimulation offer potential benefits, including reduced systemic side effects and ease of administration. This study explored the potential of a self-administered external Combined Occipital and Trigeminal Neurostimulation (eCOT-NS) device as a novel treatment option for MDD.
Trial design
The MOOD study, a completed trial designated as Phase NA, enrolled 124 participants with Major Depressive Disorder (MDD). This was a prospective, multi-center, 2-arm randomized, double-blind, parallel-group, sham-controlled study. Participants were randomized 1:1 to receive either active external Combined Occipital and Trigeminal Neurostimulation (eCOT-NS) (Relivion®DP) or sham control daily over an 8-week period. The trial aimed to evaluate the safety and efficacy of this noninvasive, self-administered treatment.
Key results
The trial reported several key measurements related to depressive symptoms:
- Mean Change in Depressive Symptoms, Measured by HDRS17 Total Score:
- Group 1 - Active Stimulation: mean -8.62 (Standard Error 0.8476 units on a scale)
- Group 2 - Sham Stimulation: mean -6.01 (Standard Error 0.8257 units on a scale)
- Percentage of Responder Participants:
- Group 1 - Active Stimulation: 15 Participants
- Group 2 - Sham Stimulation: 9 Participants
- Percentage of Subjects Achieving Remission:
- Group 1 - Active Stimulation: 10 Participants
- Group 2 - Sham Stimulation: 3 Participants
- Mean Change in Depressive Symptoms, Measured by MADRS Total Score:
- Group 1 - Active Stimulation: mean -10.18 (Standard Error 1.2874 units on a scale)
- Group 2 - Sham Stimulation: mean -8.09 (Standard Error 1.2611 units on a scale)
- Mean Change in Depressive Symptoms Severity and Improvement Scores (first measurement):
- Group 1 - Active Stimulation: mean -1.15 (Standard Error 0.1703 units on a scale)
- Group 2 - Sham Stimulation: mean -0.85 (Standard Error 0.1661 units on a scale)
- Mean Change in Depressive Symptoms Severity and Improvement Scores (second measurement):
- Group 1 - Active Stimulation: mean 3.51 (Standard Error 0.2021 units on a scale)
- Group 2 - Sham Stimulation: mean 4.05 (Standard Error 0.1975 units on a scale)
What this means
The results suggest that external Combined Occipital and Trigeminal Neurostimulation (eCOT-NS) may offer a beneficial effect for individuals with Major Depressive Disorder. The active stimulation group demonstrated greater reductions in depressive symptoms across multiple validated scales, including HDRS17 and MADRS, compared to the sham group. Furthermore, a higher number of participants in the active group achieved responder status and remission. These findings indicate that eCOT-NS could be a promising non-pharmacological option, potentially expanding the treatment landscape for MDD patients, particularly those seeking non-invasive, self-administered therapies.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT04279522, titled "The MOOD Study - External Combined Occipital and Trigeminal Nerve Stimulation (eCOT-NS) for the Treatment of Major Depressive Disorder (MDD)", were posted on 2025-08-12 on clinicaltrials.gov.