Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, Pregnancy, Brain Derived Neurotrophic Factor, Transcranial Magnetic Stimulation
Brief summary
The purpose of this study is to determine if repetitive transcranial magnetic stimulation (TMS) will alleviate symptoms of major depressive disorder (MDD) in pregnant women. TMS uses electromagnetic impulses to encourage neurons in the brain to communicate more effectively with one another. Effective neuron communication is thought to lead to the lessening of depressive symptoms. In this study subjects require daily TMS treatment for approximately four weeks.
Detailed description
We hypothesize that there will be a decline in the Hamilton Rating Scale for Depression (HDRS-17) scores from the beginning to end of treatment. We expect that this decrease will be significantly greater in subjects receiving active transcranial magnetic stimulation (TMS) compared to those receiving placebo TMS. Treatment response will be defined as greater than 50% reduction in HDRS-17 score. We also hypothesize that levels of Brain Derived Neurotrophic Factor (BDNF), a protein thought to regulate mood and cognitive functioning, will increase in subjects who respond to TMS treatment. We expect BDNF levels to increase by greater than or equal to 20% in those who respond to TMS. As previously stated, TMS response will be defined as a significant decrease (50% or greater) in the HDRS-17 from baseline to end of treatment.
Interventions
Subjects will be given active TMS 5 days per week for 4 weeks for a total of 20 sessions. Each session will last approximately 10 minutes.
DEVICESham Transcranial Magnetic Stimulation
Subjects will be given sham TMS 5 days per week for 4 weeks for a total of 20 sessions. The sham coil contains a shielding mechanism which diverts the magnetic field away from the patient. The sham treatment will last approximately 10 minutes.
Sponsors
National Institute of Mental Health (NIMH)
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 39 Years
Healthy volunteers
No
Inclusion criteria
* Subjects are capable of giving written informed consent and complying with all study procedures; * Female age 18-39 years old at date of enrollment; * Pregnant, weeks 14-34; * Current Depressive Symptoms; * No change in antidepressant medication at least two weeks prior to study entry if using an antidepressant.
Exclusion criteria
* Any alcohol or drug abuse/dependence over the 6 months prior to study entry; * History of a seizure disorder in subject or first degree relative; * Anti-psychotic, lithium, or anti-convulsant medications within 2 weeks of study enrollment; * History of known brain lesions, or severe head trauma; * Subjects with any metallic object implanted in the skull; * Subjects with significant cardiac disease; * Neurological or psychiatric disorders; * Serious medical illnesses that may compromise patient safety or study conduct; * Currently taking a drug with known potential for fetal toxicity; * Previous pregnancy with an adverse fetal outcome; * Current obstetrical complications * Actively suicidal; * History of depression unresponsive to treatment with electroconvulsive therapy (ECT).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hamilton Rating Scale for Depression (HDRS-17) Scores Pre- and Post- Treatment | Change score from baseline to test day 20 (after 20 days of intervention) | We measured changes in Hamilton Rating Scale for Depression (HDRS-17) scores from baseline to post-treatment. The HDRS-17 was administered on test days 1, 10, & 20. Scoring is based on the 17-item scale and scores of 0-7 is generally accepted to be within the normal range, indicating minimal to no depression; scores of 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression; the maximum score being 52 on the 17-point scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brain Derived Neurotrophic Factor (BDNF) With Active Transcranial Magnetic Simulation (TMS) | Change in concentration from test day 1 to test day 20 | We measured the levels of Brain Derived Neurotrophic Factor (BDNF) concentration across time. BDNF is a protein thought to regulate mood and cognitive functioning and research has suggested that levels may vary by severity of mood symptoms. We obtained BDNF values on test days 1 & 20. |
Countries
United States
Participant flow
Pre-assignment details
22 participants were eligible at screening to be enrolled into the treatment arm of the study.
Participants by arm
| Arm | Count |
|---|---|
| Active TMS 11 pregnant women in their 2nd or 3rd trimester with a primary diagnosis of MDD | 11 |
| Sham TMS 11 pregnant women in their 2nd or 3rd trimester with a primary diagnosis of MDD | 11 |
| Total | 22 |
Baseline characteristics
| Characteristic | Active TMS | Sham TMS | Total |
|---|---|---|---|
| Age, Continuous | 30.13 Years STANDARD_DEVIATION 5.78 | 26.41 Years STANDARD_DEVIATION 5.11 | 28.27 Years STANDARD_DEVIATION 5.65 |
| Region of Enrollment United States | 11 participants | 11 participants | 22 participants |
| Sex: Female, Male Female | 11 Participants | 11 Participants | 22 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 4 / 11 | 1 / 11 |
| serious Total, serious adverse events | 3 / 11 | 0 / 11 |
Outcome results
Primary
Change in Hamilton Rating Scale for Depression (HDRS-17) Scores Pre- and Post- Treatment
We measured changes in Hamilton Rating Scale for Depression (HDRS-17) scores from baseline to post-treatment. The HDRS-17 was administered on test days 1, 10, & 20. Scoring is based on the 17-item scale and scores of 0-7 is generally accepted to be within the normal range, indicating minimal to no depression; scores of 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression; the maximum score being 52 on the 17-point scale.
Time frame: Change score from baseline to test day 20 (after 20 days of intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active TMS | Change in Hamilton Rating Scale for Depression (HDRS-17) Scores Pre- and Post- Treatment | -13.909 difference in units on a scale | Standard Deviation 5.224 |
| Sham TMS | Change in Hamilton Rating Scale for Depression (HDRS-17) Scores Pre- and Post- Treatment | -9.091 difference in units on a scale | Standard Deviation 7.582 |
Comparison: This analysis is based on a mixed model that can handle missing data.p-value: 0.003Fisher Exact
Secondary
Change in Brain Derived Neurotrophic Factor (BDNF) With Active Transcranial Magnetic Simulation (TMS)
We measured the levels of Brain Derived Neurotrophic Factor (BDNF) concentration across time. BDNF is a protein thought to regulate mood and cognitive functioning and research has suggested that levels may vary by severity of mood symptoms. We obtained BDNF values on test days 1 & 20.
Time frame: Change in concentration from test day 1 to test day 20
Population: Only 4 participants from both the active and sham TMS groups were used in analysis because these participants had BDNF data at both time points. Furthermore, some samples were deemed unusable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active TMS | Change in Brain Derived Neurotrophic Factor (BDNF) With Active Transcranial Magnetic Simulation (TMS) | 146.8775 pg/mL | Standard Deviation 235.6441 |
| Sham TMS | Change in Brain Derived Neurotrophic Factor (BDNF) With Active Transcranial Magnetic Simulation (TMS) | 40.0550 pg/mL | Standard Deviation 131.9466 |
Comparison: This analysis is based on a mixed model that can handle missing data.p-value: 0.425Regression, Logistic