Major Depressive Disorder
Conditions
Keywords
depression, Major Depressive Disorder, MDD, Cranial Electrical Stimulation, CES
Brief summary
The purpose of this study is to see if using Cranial Electrical Stimulation (CES) helps improve symptoms of major depressive disorder (MDD). The investigators are studying the device's effectiveness in treating depression, as well as its safety. This is a pilot study. Eligible participants will be randomly assigned to receive either active CES or sham CES, every weekday for 3 weeks. During the visits, subjects will receive CES or sham CES treatment for 20 minutes. The primary outcome measure will be change in score on the HAM-D 17. The secondary outcome measure will be change in patient-reported sleep score.
Detailed description
We examined efficacy and safety of one specific cranial electrical stimulator (CES) device at a fixed setting in subjects with treatment-resistant major depressive disorder (MDD). Thirty subjects with MDD and inadequate response to standard antidepressants were randomized to 3 weeks of treatment with CES (15/500/15000 Hz, symmetrical rectangular biphasic current of 1-4 mAmp, 40 Volts) or sham CES (device off) for 20 minutes, 5 days per week. The primary outcome measure was improvement in the 17-item Hamilton Depression Rating Scale (HAM-D-17). Adverse effects (AEs) were assessed using the Patient Related Inventory of Side Effects (PRISE). We hypothesized that subjects who received active as opposed to sham CES would have a significantly greater improvement in their depression symptoms. Due to the small sample, we could not hypothesize an effect size, but would calculate one to determine signal strength to guide the design of a larger, more rigorous study. As an exploratory aim, we also examined whether CES would benefit sleep.
Interventions
DEVICEActive CES
CES current
DEVICESham CES
Sham CES (device off) for 20-minutes each day 5 days/week for 3 weeks.
Sponsors
Fisher Wallace Labs, LLC
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Subjects must meet all of the following criteria to participate in the study: 1. Age 18-65 years old 2. Be in generally good health 3. Meet criteria for Major Depressive Disorder based on the DSM-IV 4. HAM-D-17 score ≥ 15, and ≤ 23
Exclusion criteria
Subjects meeting any of the following criteria will not be allowed to participate in the study: 1. Taking any antidepressant medications (including natural products such as omega-3, St John's wort, and/or SAMe) 2. Having any unstable health conditions (unstable cardiovascular illness, cardiac arrhythmia, presence of a pacemaker, epilepsy and shock, fever, weakness and hypotension, or presence of a vagal nerve stimulator) 3. Having any electrical stimulation implants - i.e. pacemaker, deep brain stimulators (VNS, DBS), transcutaneous electrical nerve stimulator (TENS) 4. Psychotic or manic symptoms, or other evidence of a psychotic disorder; recent history of substance abuse or dependence 5. Electro Convulsive Therapy (ECT) during the last year 6. Previous course of Cranial Electrical Stimulation 7. Current active suicidal or self-injurious potential necessitating immediate treatment 8. In women, pregnancy, plans to conceive, or unwillingness to comply with birth control requirements 9. Depression-focused psychotherapy initiated within 90 days preceding enrollment or during participation in study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hamilton Depression Rating Scale (HAM-D 17) Score From Baseline to Week 3 | Baseline-Week 3 | The Hamilton Depression Rating Scale (HAM-D-17) used here is a 17-item scale that measures severity of depression. Items are individually scored from 0-4 or from 0-2 depending on the item, and the individual scores for each item are added to comprise one score. Higher scores indicate greater severity of depression. Possible scores on the scale range from a minimum of zero (0) to a maximum of 52. This section reports the improvement in depressive symptoms during the course of treatment, i.e. the change in overall score between baseline visit and week 3 visit. Change can occur in either direction (i.e. improvement or worsening). A score of greater than zero indicates a reduction of depressive symptoms (improvement), whereas a score of less than zero indicates an increase in depressive symptoms (worsening). |
| Reported Side Effects Based on PRISE AE Scores | Baseline-Week 3 | This measures the emergence of different adverse (side) effects from treatment during the study. This section will describe the most commonly reported adverse effects. The section on adverse events will describe and detail the full range of AEs reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Global Sleep Scores on the Pittsburgh Sleep Quality Index (PSQI) From Baseline to Week 3. | Baseline-Week 3 | The Pittsburgh Sleep Quality Index (PSQI) is a patient-rated instrument to assess sleep quality and quantity and its changes throughout the study. Scoring is based on 7 individual components. Each component is scored from 0-3. Higher scores indicate worse sleep. Total global sleep score ranges from zero (0) to 21. We report here the overall change in global sleep score for each treatment arm, i.e. the change in overall score between baseline visit and week 3 visit. Change can occur in either direction (i.e. improvement or worsening). A score of greater than zero indicates a reduction of sleep disturbance (improvement), whereas a score of less than zero indicates an increase in sleep disturbance (worsening). |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited by advertisement from our Depression Clinical and Research Program (DCRP). Informed consent was obtained per IRB guidelines. Investigators who screened subjects were our program's psychiatrists and psychologists, trained and certified in the use of appropriate diagnostic instruments such as the SCID and HAM-D.
Pre-assignment details
Subjects who passed the screen visit returned a week later for the baseline visit. At that time, subjects received their first treatment (or sham) at the site for 20 minutes, including personal instruction of proper technique and electrode placement.
Participants by arm
| Arm | Count |
|---|---|
| Active CES Active CES: The FW-100 Cranial Stimulator headset was placed on the scalp over the two dorsolateral prefrontal cortex areas. The power knob was turned to maximum setting. The waveform contains a 15000Hz square wave carrier from 0-4 mAmp. The first 15Hz modulating signal provides 50msec of on and 16.7msec of off time (total 66.7msec, 50% duty cycle). A second 500Hz modulating signal changes the on time series of 15000Hz pulses (750 pulses/50msec) into 25 smaller bursts of 15 pulses of the 15000Hz carrier signal, for 375 pulses in 50msec. The consecutive positive burst and off time is followed by an opposite negative burst and off time, balancing the current component to zero. Output voltage ranges from 0-40V, positive and negative. CES automatically shut off after 20 mins.
Active CES: CES current | 17 |
| Sham CES Shame CES: The sham devices were modified to not deliver current to the headset. The current from the active device departs from the posts at the top of the device into the headsets, creating a loop when the headset is worn by the subject with the wet electrode sponges. This loop is eliminated in the sham devices by wrapping wire around the posts, thus containing the loop within the device, with no electricity leaving the headsets. This approach allows the loop to be maintained, and therefore all of the device's green and yellow amperage lights still light up, protecting the blind.
Sham CES: Sham CES (device off) for 20-minutes each day 5 days/week for 3 weeks. | 13 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Active CES | Sham CES | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 13 Participants | 30 Participants |
| Age, Continuous | 45.5 years STANDARD_DEVIATION 12.3 | 51.4 years STANDARD_DEVIATION 11.9 | 48.1 years STANDARD_DEVIATION 12.3 |
| Hamilton Depression Rating Scale | 18.1 units on a scale STANDARD_DEVIATION 1.5 | 18.7 units on a scale STANDARD_DEVIATION 3.9 | 18.3 units on a scale STANDARD_DEVIATION 2.8 |
| Region of Enrollment United States | 17 participants | 13 participants | 30 participants |
| Sex: Female, Male Female | 10 Participants | 7 Participants | 17 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 17 | 8 / 13 |
| serious Total, serious adverse events | 0 / 17 | 0 / 13 |
Outcome results
Primary
Change in Hamilton Depression Rating Scale (HAM-D 17) Score From Baseline to Week 3
The Hamilton Depression Rating Scale (HAM-D-17) used here is a 17-item scale that measures severity of depression. Items are individually scored from 0-4 or from 0-2 depending on the item, and the individual scores for each item are added to comprise one score. Higher scores indicate greater severity of depression. Possible scores on the scale range from a minimum of zero (0) to a maximum of 52. This section reports the improvement in depressive symptoms during the course of treatment, i.e. the change in overall score between baseline visit and week 3 visit. Change can occur in either direction (i.e. improvement or worsening). A score of greater than zero indicates a reduction of depressive symptoms (improvement), whereas a score of less than zero indicates an increase in depressive symptoms (worsening).
Time frame: Baseline-Week 3
Population: Intent to treat sample with last observation carried forward for all randomized subject.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CES | Change in Hamilton Depression Rating Scale (HAM-D 17) Score From Baseline to Week 3 | 14.8 units on a scale | Standard Deviation 6.3 |
| Sham CES | Change in Hamilton Depression Rating Scale (HAM-D 17) Score From Baseline to Week 3 | 13.6 units on a scale | Standard Deviation 5.8 |
Primary
Reported Side Effects Based on PRISE AE Scores
This measures the emergence of different adverse (side) effects from treatment during the study. This section will describe the most commonly reported adverse effects. The section on adverse events will describe and detail the full range of AEs reported.
Time frame: Baseline-Week 3
Population: Intent to treat sample with all subjects randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Active CES | Reported Side Effects Based on PRISE AE Scores | Poor concentration | 10 number of subjects reporting |
| Active CES | Reported Side Effects Based on PRISE AE Scores | Decreased energy | 6 number of subjects reporting |
| Active CES | Reported Side Effects Based on PRISE AE Scores | Fatigue | 5 number of subjects reporting |
| Active CES | Reported Side Effects Based on PRISE AE Scores | Anxiety | 5 number of subjects reporting |
| Active CES | Reported Side Effects Based on PRISE AE Scores | Flashing light/tingling | 5 number of subjects reporting |
| Sham CES | Reported Side Effects Based on PRISE AE Scores | Flashing light/tingling | 0 number of subjects reporting |
| Sham CES | Reported Side Effects Based on PRISE AE Scores | Anxiety | 4 number of subjects reporting |
| Sham CES | Reported Side Effects Based on PRISE AE Scores | Decreased energy | 2 number of subjects reporting |
| Sham CES | Reported Side Effects Based on PRISE AE Scores | Poor concentration | 2 number of subjects reporting |
| Sham CES | Reported Side Effects Based on PRISE AE Scores | Fatigue | 2 number of subjects reporting |
Secondary
Change in Global Sleep Scores on the Pittsburgh Sleep Quality Index (PSQI) From Baseline to Week 3.
The Pittsburgh Sleep Quality Index (PSQI) is a patient-rated instrument to assess sleep quality and quantity and its changes throughout the study. Scoring is based on 7 individual components. Each component is scored from 0-3. Higher scores indicate worse sleep. Total global sleep score ranges from zero (0) to 21. We report here the overall change in global sleep score for each treatment arm, i.e. the change in overall score between baseline visit and week 3 visit. Change can occur in either direction (i.e. improvement or worsening). A score of greater than zero indicates a reduction of sleep disturbance (improvement), whereas a score of less than zero indicates an increase in sleep disturbance (worsening).
Time frame: Baseline-Week 3
Population: This is an intent to treat (ITT) analysis of all patients randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CES | Change in Global Sleep Scores on the Pittsburgh Sleep Quality Index (PSQI) From Baseline to Week 3. | 0.33 units on a scale | Standard Deviation 2.02 |
| Sham CES | Change in Global Sleep Scores on the Pittsburgh Sleep Quality Index (PSQI) From Baseline to Week 3. | 0.77 units on a scale | Standard Deviation 2.17 |