Depression
Conditions
Keywords
Electric Stimulation, Magnetic Stimulation, Prefrontal Cortex, Brain
Brief summary
This study will evaluate the safety and effectiveness of magnetic brain stimulation for the treatment of major depression in depressed adults with moderate treatment resistance.
Detailed description
Major depression is a type of depression that can interfere with the ability to work, study, sleep, eat, and enjoy once pleasurable activities. Because people often develop resistances to medications used to treat depression, new treatments are needed. Decreased electrical activity in the prefrontal region of the brain has been linked to some symptoms of depression. Repetitive transcranial magnetic stimulation (rTMS) can be used to influence the brain's electrical activity. This procedure entails attaching electrodes to the head and using a device to pass magnetic energy through coils and into the brain. rTMS has been shown to have antidepressant effects in depressed individuals. However, optimal levels of intensity and treatment duration have yet to be determined. This study will assess the safety and effectiveness of rTMS on the prefrontal region of the brain in depressed adults with moderate treatment resistance. The treatment phase of this double-blind study will last a minimum of 32 weeks and will consist of 3 phases. In Phase I, participants will be randomly assigned to receive either rTMS or sham stimulation. The sham stimulation will mimic the sensation of rTMS but will not induce an intracerebral current. Treatments will be administered daily for 3 weeks. Participants who show signs of improvement may continue Phase I for up to 3 additional weeks. In Phase II, participants who were unresponsive to Phase I treatment will receive daily rTMS at a lower dose for 3 weeks. Participants who show signs of improvement, but have not achieved remission, may continue Phase II for 4 additional weeks. Baseline magnetic resonance images will be used to determine the optimal stimulus intensity by adjusting for individual differences in cortical to skull distances. Phase III participants will be only those who achieved remission in the first 2 phases. These participants will receive antidepressant medication treatment daily for six months. Participants' functional status and symptoms of depression will be measured using self-report scales and video-recorded interviews at study start date and at the end of each treatment phase.
Interventions
PROCEDUREPrefrontal rTMS
Participants receive 120% motor threshold (MT) over left and right prefrontal cortex. Treatments will be administered daily for 3 weeks. Participants who show signs of improvement may continue Phase I for up to 3 additional weeks.
DRUGAntidepressant Regimen
Particpants who acheive remission with rTMS may start antidepressant medication in phase III.
PROCEDURESham Stimulation
The sham stimulation will mimic the sensation of rTMS but will not induce an intracerebral current. Treatments will be administered daily for 3 weeks.
Sponsors
National Institute of Mental Health (NIMH)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of major depression with a current episode * Hamilton Rating Scale for Depression score higher than 20 * No response or intolerance to antidepressant medication in the current depressive episode
Exclusion criteria
* Current use of antidepressants * Diagnosis of psychosis or anxiety disorder * Current substance abuse * Seizures or history of head trauma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Depression Remission, as Measured by the Hamilton Rating Scale for Depression | Measured at the end of Phases 1, 2, and 3 | The Hamilton Rating Scale for Depression 17-item total score ranges from 0 to 52 with higher scores indicating more depression. Remission is defined as a total score of ≤ 8 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active TMS Phase I participants receiving rTMS
Prefrontal Repetitive Transcranial Magnetic Stimulation (rTMS): Participants receive 120% motor threshold (MT) over left and right prefrontal cortex. Treatments will be administered daily for 3 weeks. Participants who show signs of improvement may continue Phase I for up to 3 additional weeks. | 92 |
| Sham TMS Phase I participants receiving sham stimulation
Sham Stimulation: The sham stimulation will mimic the sensation of rTMS but will not induce an intracerebral current. Treatments will be administered daily for 3 weeks. | 98 |
| Total | 190 |
Baseline characteristics
| Characteristic | Total | Active TMS | Sham TMS |
|---|---|---|---|
| Age, Continuous | 47.1 years STANDARD_DEVIATION 11.5 | 47.7 years STANDARD_DEVIATION 10.6 | 46.5 years STANDARD_DEVIATION 12.3 |
| Sex: Female, Male Female | 105 Participants | 55 Participants | 50 Participants |
| Sex: Female, Male Male | 85 Participants | 37 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 18 / 92 | 15 / 98 | 0 / 144 | 0 / 61 |
| serious Total, serious adverse events | 0 / 92 | 0 / 98 | 0 / 144 | 0 / 61 |
Outcome results
Primary
Depression Remission, as Measured by the Hamilton Rating Scale for Depression
The Hamilton Rating Scale for Depression 17-item total score ranges from 0 to 52 with higher scores indicating more depression. Remission is defined as a total score of ≤ 8
Time frame: Measured at the end of Phases 1, 2, and 3
Population: Remission
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active TMS | Depression Remission, as Measured by the Hamilton Rating Scale for Depression | 13 number of remitted patients |
| Sham TMS | Depression Remission, as Measured by the Hamilton Rating Scale for Depression | 5 number of remitted patients |
| Active Open for 3 Weeks | Depression Remission, as Measured by the Hamilton Rating Scale for Depression | 43 number of remitted patients |
| Medication Followup | Depression Remission, as Measured by the Hamilton Rating Scale for Depression | 12 number of remitted patients |