Functional Electrical Stimulation for MDD

Functional Electrical Stimulation for Major Depressive Disorder: A Pilot Randomized Control Trial

This study aims to determine whether Functional Electrical Stimulation (FES) of the facial muscles is a safe and effective treatment for major depressive disorder (MDD).

Study Overview

• Status: Not yet recruiting
• Conditions: MDD
• Intervention / Treatment: Device: Functional Electrical Stimulation (FES)

Detailed Description

A potential new treatment for Major Depressive Disorder (MDD) involves using a Functional Electrical Stimulation (FES) device to stimulate specific facial muscles. By targeting muscles related to smile patterns, FES has shown promise in improving emotional control and boosting mood. This project aims to address a critical need for innovative treatments for MDD, especially since 30% of MDD patients do not respond to traditional treatments.

This is a single-site clinical trial that is double-blind, randomized, and sham-controlled, involving 20 sessions of FES over four weeks. The trial will assess the effectiveness, safety, and tolerability of FES for individuals with mild-to-moderate major depressive episode (MDE) and a primary diagnosis of MDD.

Participants in the study will have a total of 26 visits: one screening and one baseline visit (both conducted by phone), followed by 20 on-site intervention visits over four weeks (one sessions per day). After the treatment, there will also be four follow-up visits over the phone to check how long the effects of the FES treatment last.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Venkat Bhat; Phone Number: 76404 416-360-4000; Email: Venkat.Bhat@unityhealth.to

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients will be included if they:

1. Meet the DSM-5 criteria for unipolar MDD with a current MDE without psychotic features, with ≤ 2 failed treatment trials (non-treatment-resistant depression), validated by MINI done by a trained research assistant.
2. Have no change in the medication regimen or other forms of treatments (e.g., psychotherapy) for at least 4 weeks (28 days) prior to beginning the study, and have no plan to change them during the 20-session treatment period (14 days), and the 4-week post-treatment observation period. This will be established through self-report, in combination with the ATHF filled out by the participant.
3. Have an MDD diagnosis as confirmed by the MADRS score of ≥7.
4. Age group between 18 and 70 years of age

Exclusion Criteria:

Patients will be excluded if they:

1. History of epilepsy or seizures.
2. Damage or dysfunction of facial nerves.
3. Metallic orthopedic implants in the mouth (e.g., plates or screws).
4. Current fibromyalgia or currently receiving or have received rTMS within the last 28 days before the screening.
5. History of treatment-resistant depression (TRD) with history of ECT, Magnetic Seizure Therapy, Intravenous Ketamine use in the past or failure of >2 antidepressant treatments of adequate duration and dose during the current episode.
6. Past or current symptoms of mania, hypomania, mixed episodes, psychotic disorders, obsessive-compulsive disorder, post-traumatic stress disorder, active substance abuse or dependence (excluding nicotine and caffeine), neurodegenerative disease, or dementia. This will be confirmed on the MINI (77) administered by a trained research assistant.
7. Current suicidal intent or plan as demonstrated by a score of ≥4 on MADRS item 10.
8. Unable to understand instructions in English.
9. Unable to produce "Duchenne marker" expression with FES, secondary to any type of neurological condition or previous botulinum toxin treatments of facial muscles.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active FES; Participants in the active group will receive FES on four facial muscles involved in smiling (two on each side of the face). Electrodes will be placed on these muscles, and stimulation will be delivered using an FES device with standard muscle-activation settings. The stimulation will follow repeated cycles of 15 seconds ON and 15 seconds OFF. While receiving FES, participants will watch positive or comedy videos. They will also be encouraged to voluntarily produce a natural smile during stimulation. After each smile, participants will press a button to confirm they followed the instruction.	Device: Functional Electrical Stimulation (FES); Once per day for the duration of 4 weeks. Total of 20 sessions (each session lasts 60 mins)
Sham Comparator: Sham FES; Participants recruited to the sham arm will also receive FES of the facial muscles in the same setup as the experimental group, but with only sensory stimulation (in the range of 1-8 mA stimulation - just enough to feel the stimulation, with other parameters the same as active arm) and in a non-Duchenne smile pattern.	Device: Functional Electrical Stimulation (FES); Once per day for the duration of 4 weeks. Total of 20 sessions (each session lasts 60 mins)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of FES: Change in Depression Severity	Change in depression severity measured using the 17-item Hamilton Depression Rating Scale (HAM-D-17). Scores range from 0 to 52, with higher scores indicating more severe depressive symptoms.	4 weeks of Intervention, 4 weeks of follow-up
Tolerability of FES	The overall dropout and protocol compliance rates will be assessed.	4 weeks of Intervention, 4 weeks of follow-up
FES safety	The number and nature of adverse events will be assessed	4 weeks of Intervention, 4 weeks of follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Anxiety Symptoms	Anxiety symptoms will be assessed using the Generalized Anxiety Disorder-7. Total scores range from 0 to 21, with higher scores indicating greater anxiety symptom severity.	4 weeks of Intervention, 4 weeks of follow-up
Change in Well-Being	Well-being will be assessed using the World Health Organization-Five Well-Being Index. Raw total scores range from 0 to 25, with higher scores indicating better well-being.	4 weeks of Intervention, 4 weeks of follow-up
Change in Sleep Quality	Sleep quality will be assessed using the Pittsburgh Sleep Quality Index. Global scores range from 0 to 21, with higher scores indicating poorer sleep quality.	4 weeks of Intervention, 4 weeks of follow-up
Response and Remission Rate	Response and Remission will be assessed using the 17-item Hamilton Depression Rating Scale. Total scores on the 17-item Hamilton Depression Rating Scale range from 0 to 52, with higher scores indicating greater depression symptom severity.	4 weeks of Intervention, 4 weeks of follow-up
Changes in Facial Expressivity	Changes in facial expressivity (frequency, intensity and duration of Duchenne smiles) will be assessed during an emotional interview, using objective facial coding.	4 weeks of Intervention

Collaborators and Investigators

• Sponsor: Unity Health Toronto

Study record dates

Study Major Dates

• Study Start (Estimated): May 25, 2026
• Primary Completion (Estimated): April 20, 2028
• Study Completion (Estimated): March 30, 2029

Study Registration Dates

• First Submitted: May 25, 2026
• First Submitted That Met QC Criteria: June 2, 2026
• First Posted (Actual): June 5, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Major Depressive Disorder; Functional Electrical Stimulation
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 24-155; WI4 179978 (Other Grant/Funding Number: Canadian Institutes of Health Research (CIHR))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No