Bipolar Depression
Conditions
Keywords
Low Field Magnetic Stimulation, bipolar, depression, alternative treatment
Brief summary
Objectives: To demonstrate the duration of the antidepressant effect of Low Field Magnetic Stimulation (LFMS)in subjects with bipolar depression. Hypotheses: Investigators expect subjects who receive LFMS to show significant mood improvement one week after the start of a three day course of daily stimulation as compared to subjects who receive sham LFMS. Investigators expect subjects who receive LFMS to show immediate mood improvement over the first treatment as measured by the difference in pre and post-treatment PANAS+ ratings. Investigators expect to show that LFMS will be well tolerated in a three-treatment protocol.
Detailed description
Low Field Magnetic Stimulation is an electromagnetic intervention being investigated at McLean Hospital because of its effect on symptoms of depression. It consists of pulsed electric fields that are induced remotely in the head by a portable coil. It has been observed to have mood elevating effects in depressed patients with Bipolar Disorder (BPD). These effects are immediate, occurring upon completion of a 20 minute treatment. LFMS is unique because of its low electric field strength, and because of its high frequency operation, compared to other electromagnetic treatments. While other treatments such as Electroconvulsive Therapy (ECT) use electric fields equivalent to \> 100-200 Volts/meter to affect the brain, LFMS uses \<1 V/m. Such a low electric field strength indicates that another mechanism is activated by LFMS, and this provides a possibility for a new treatment. It may also give insight into causes of depression. LFMS is also unique because it has an immediate effect. This immediate effect may have implications for emergency treatment. The purpose of this study is to observe the response to LFMS in depressed BPD subjects with the aim of assessing the effects of multiple treatments, and of observing the duration of the mood improvement.To do so, the investigators propose to study 72 subjects in a protocol of three treatments in three days. Subjects will be rated before and after each treatment, and will return for mood ratings at one week after treatment. Investigators hope that this characterization of LFMS will allow clinical research groups to perform large trials and to evaluate its clinical effectiveness in patient populations.
Interventions
Low Field Magnetic Stimulation is an electromagnetic technique. It uses low strength electric fields operating at a high frequency.
Sponsors
The Depressive and Bipolar Disorder Alternative Treatment Foundation
Mclean Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects will be men or women between the ages of 21-65. 2. Subjects must not have serious physical illnesses, neurological diseases or dementias. 3. Subjects will meet DSM-IV criteria for Bipolar Disorder Type I or II and meet criteria for current depression (DSM-IV major depressive episode, current). 4. Subject must have a MADRS \>= 20, Young Mania Rating Score (YMRS score) \< 7. 5. Subjects must be capable of providing informed consent. 6. Subjects must have an established residence and phone. 7. Subjects may be medicated or unmedicated.
Exclusion criteria
1. Dangerous or active suicidal ideation. 2. Pregnant or planning on becoming pregnant. 3. Substance abuse (cannot meet DSM criteria for substance abuse, no significant drug abuse within last 3 months, no major polysubstance abuse history, no history of dependence in last year, no drug use within last month). 4. Mania, hypomania or mixed mood state. 5. Significant medical or neurological illness that might pose a risk to study enrollment or interfere with interpretation of study data. 6. Changes in psychiatric medication (e.g. dose or drug) within 6 weeks prior to enrollment. 7. History of schizophrenia, schizoaffective, obsessive-compulsive or post-traumatic stress disorders. 8. Treatment resistant depression (as determined by the study psychiatrist; consistently and substantially symptomatic over several years despite electroconvulsive therapy, 2 or more adequate trials of a primary mood stabilizer with antidepressant effects (e.g., lithium, valproate or lamotrigine) or antidepressant medications (e.g., bupropion, Selective Serotonin Reuptake Inhibitors (SSRI) or Serotonin Norepinephrine Reuptake Inhibitor (SNRI).) 9. Contraindications for Magnetic Resonance Imaging (MRI): Presence of a pacemaker, neurostimulator, or metal in head or neck.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Long Term Change: Montgomery-Åsberg Depression Rating Scale (MADRS) | Variable based on screening visit schedule, > 2 weeks. | The Montgomery-Asberg Depression Rating scale assesses 10 symptom areas of depression during an interview. Each of the 10 items received a score ranging from 0 to 6. The scale has a range of 0-60 for the reported total. A higher score indicates increased depression for all items and for the total. This outcome measure is the change from pretreatment baseline acquired at the screening visit to a follow-up visit 7 days after the first treatment. |
| Change Over First Treatment: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | 90 minutes; change immediately (<30min) prior to the first treatment and immediately after (<30min) the first treatment. | PANAS consists of 10 positive and 10 negative valence word items. Items are rated by the participant to indicate their assessment of how they are feeling about this item right now on a scale of 1(slightly) or not at all through 5 (extremely). 10 of of the items form a positive affect subscale, in which a higher score indicates increased positive affect, with a subscale range of 10 to 50. 10 of the items form a negative affect subscale, in which a higher score indicates more negative affect, with a subscale range of 10 to 50. This outcome measure is change in the 10 item positive affect subscale. This outcome measure is the difference between the scale administered immediately (\<30min) prior to the first treatment and immediately after (\<30min) the first treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of of Change in Daily Improvement Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | Over 3 days of treatment | PANAS consists of 10 positive and 10 negative valence word items. Items are rated by the participant to indicate their assessment of how they are feeling about this item right now on a scale of 1(slightly) or not at all through 5 (extremely). 10 of of the items form a positive affect subscale, in which a higher score indicates increased positive affect, with a subscale range of 10 to 50. 10 of the items form a negative affect subscale, in which a higher score indicates more negative affect, with a subscale range of 10 to 50. This outcome measure uses the 10 item positive affect subscale. This outcome measure is the least squares fit of a linear coefficient to the three post (\<30min oost treatment) minus pre (\<30min pre treatment) score differences for the three treatment days |
| Rate of Change Over 3 Treatments: Montgomery-Asberg Depression Rating Scale (MADRS) | Over 3 days of treatment | The Montgomery-Asberg Depression Rating scale assesses 10 symptom areas of depression during an interview. Each of the 10 items received a score ranging from 0 to 6. The scale has a range of 0-60 for the reported total. A higher score indicates increased depression for all items and for the total. This outcome measure is the least squares fit of a linear coefficient to the three pretreatment scores for the three treatment days |
| Rate of Change Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | Over 3 days of treatment | PANAS consists of 10 positive and 10 negative valence word items. Items are rated by the participant to indicate their assessment of how they are feeling about this item right now on a scale of 1(slightly) or not at all through 5 (extremely). 10 of of the items form a positive affect subscale, in which a higher score indicates increased positive affect, with a subscale range of 10 to 50. 10 of the items form a negative affect subscale, in which a higher score indicates more negative affect, with a subscale range of 10 to 50. This outcome measure uses the 10 item positive affect subscale. This outcome measure is the least squares fit of a linear coefficient to the three pretreatment scores for the three treatment days |
Countries
United States
Participant flow
Recruitment details
Recruitment was performed through newspaper advertisement, posting, and referral
Pre-assignment details
Subjects that failed exclusion criteria for variable criteria such as medications change or drug use were permitted to reapply for participation after a washout period of at least 1 month.
Participants by arm
| Arm | Count |
|---|---|
| LFMS - Active Treatment Low Field Magnetic Stimulation (LFMS) active treatment
Active low field magnetic stimulation treatment applied with the LFMS Device; the device is on and magnetic field stimulation is present.
Low Field Magnetic Stimulation: Low Field Magnetic Stimulation is an electromagnetic technique. It uses low strength electric fields operating at a high frequency. | 28 |
| LFMS - Sham Treatment Low Field Magnetic Stimulation - sham treatment
Inactive low field magnetic stimulation (no stimulation) treatment applied with the LFMS Device; the device is on, however no magnetic field stimulation is present.
Low Field Magnetic Stimulation: Low Field Magnetic Stimulation is an electromagnetic technique. It uses low strength electric fields operating at a high frequency. | 25 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | LFMS - Active Treatment | LFMS - Sham Treatment |
|---|---|---|---|
| Age, Continuous | 45.1 years STANDARD_DEVIATION 12 | 44.5 years STANDARD_DEVIATION 13.5 | 45.7 years STANDARD_DEVIATION 10.3 |
| Montgomery-Asberg Depression Rating Scale (MADRS) | 27.8 units on a scale STANDARD_DEVIATION 5.4 | 28.2 units on a scale STANDARD_DEVIATION 5.8 | 27.4 units on a scale STANDARD_DEVIATION 5 |
| Sex: Female, Male Female | 23 Participants | 13 Participants | 10 Participants |
| Sex: Female, Male Male | 30 Participants | 15 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 24 |
| other Total, other adverse events | 1 / 26 | 0 / 24 |
| serious Total, serious adverse events | 0 / 26 | 0 / 24 |
Outcome results
Primary
Change Over First Treatment: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale
PANAS consists of 10 positive and 10 negative valence word items. Items are rated by the participant to indicate their assessment of how they are feeling about this item right now on a scale of 1(slightly) or not at all through 5 (extremely). 10 of of the items form a positive affect subscale, in which a higher score indicates increased positive affect, with a subscale range of 10 to 50. 10 of the items form a negative affect subscale, in which a higher score indicates more negative affect, with a subscale range of 10 to 50. This outcome measure is change in the 10 item positive affect subscale. This outcome measure is the difference between the scale administered immediately (\<30min) prior to the first treatment and immediately after (\<30min) the first treatment.
Time frame: 90 minutes; change immediately (<30min) prior to the first treatment and immediately after (<30min) the first treatment.
Population: subjects completing 3 treatment visits and 1 followup visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LFMS - Active Treatment | Change Over First Treatment: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | 0.5 units on a scale | Standard Deviation 5.8 |
| LFMS - Sham Treatment | Change Over First Treatment: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | 1.4 units on a scale | Standard Deviation 5.32 |
p-value: <0.182Regression, Linear
Primary
Long Term Change: Montgomery-Åsberg Depression Rating Scale (MADRS)
The Montgomery-Asberg Depression Rating scale assesses 10 symptom areas of depression during an interview. Each of the 10 items received a score ranging from 0 to 6. The scale has a range of 0-60 for the reported total. A higher score indicates increased depression for all items and for the total. This outcome measure is the change from pretreatment baseline acquired at the screening visit to a follow-up visit 7 days after the first treatment.
Time frame: Variable based on screening visit schedule, > 2 weeks.
Population: Subjects completing 3 treatments and 1 visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LFMS - Active Treatment | Long Term Change: Montgomery-Åsberg Depression Rating Scale (MADRS) | -14.03 units on a scale | Standard Deviation 7.85 |
| LFMS - Sham Treatment | Long Term Change: Montgomery-Åsberg Depression Rating Scale (MADRS) | -9.75 units on a scale | Standard Deviation 9.32 |
p-value: <0.049Regression, Linear
Secondary
Rate of Change Over 3 Treatments: Montgomery-Asberg Depression Rating Scale (MADRS)
The Montgomery-Asberg Depression Rating scale assesses 10 symptom areas of depression during an interview. Each of the 10 items received a score ranging from 0 to 6. The scale has a range of 0-60 for the reported total. A higher score indicates increased depression for all items and for the total. This outcome measure is the least squares fit of a linear coefficient to the three pretreatment scores for the three treatment days
Time frame: Over 3 days of treatment
Population: Subjects completing 3 treatments and 1 visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFMS - Active Treatment | Rate of Change Over 3 Treatments: Montgomery-Asberg Depression Rating Scale (MADRS) | linear coefficient | -5.42 units on a scale | Standard Error 1.07 |
| LFMS - Active Treatment | Rate of Change Over 3 Treatments: Montgomery-Asberg Depression Rating Scale (MADRS) | day 1 mean | 26.15 units on a scale | Standard Error 1.47 |
| LFMS - Active Treatment | Rate of Change Over 3 Treatments: Montgomery-Asberg Depression Rating Scale (MADRS) | day 2 mean | 16.81 units on a scale | Standard Error 1.31 |
| LFMS - Active Treatment | Rate of Change Over 3 Treatments: Montgomery-Asberg Depression Rating Scale (MADRS) | day 3 mean | 15.31 units on a scale | Standard Error 1.69 |
| LFMS - Sham Treatment | Rate of Change Over 3 Treatments: Montgomery-Asberg Depression Rating Scale (MADRS) | day 3 mean | 14.92 units on a scale | Standard Error 1.66 |
| LFMS - Sham Treatment | Rate of Change Over 3 Treatments: Montgomery-Asberg Depression Rating Scale (MADRS) | linear coefficient | -5.60 units on a scale | Standard Error 1.07 |
| LFMS - Sham Treatment | Rate of Change Over 3 Treatments: Montgomery-Asberg Depression Rating Scale (MADRS) | day 2 mean | 17.83 units on a scale | Standard Error 1.45 |
| LFMS - Sham Treatment | Rate of Change Over 3 Treatments: Montgomery-Asberg Depression Rating Scale (MADRS) | day 1 mean | 26.13 units on a scale | Standard Error 1.44 |
p-value: <0.444Regression, Linear
Secondary
Rate of Change Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale
PANAS consists of 10 positive and 10 negative valence word items. Items are rated by the participant to indicate their assessment of how they are feeling about this item right now on a scale of 1(slightly) or not at all through 5 (extremely). 10 of of the items form a positive affect subscale, in which a higher score indicates increased positive affect, with a subscale range of 10 to 50. 10 of the items form a negative affect subscale, in which a higher score indicates more negative affect, with a subscale range of 10 to 50. This outcome measure uses the 10 item positive affect subscale. This outcome measure is the least squares fit of a linear coefficient to the three pretreatment scores for the three treatment days
Time frame: Over 3 days of treatment
Population: Subjects completing 3 treatments and 1 visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFMS - Active Treatment | Rate of Change Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | linear coefficient | 1.70 units on a scale | Standard Error 1.39 |
| LFMS - Active Treatment | Rate of Change Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | day 1 mean | 21.00 units on a scale | Standard Error 1.82 |
| LFMS - Active Treatment | Rate of Change Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | day 2 mean | 24.04 units on a scale | Standard Error 1.95 |
| LFMS - Active Treatment | Rate of Change Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | day 3 mean | 24.40 units on a scale | Standard Error 2.21 |
| LFMS - Sham Treatment | Rate of Change Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | day 3 mean | 23.85 units on a scale | Standard Error 1.84 |
| LFMS - Sham Treatment | Rate of Change Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | linear coefficient | 0.80 units on a scale | Standard Error 1.1 |
| LFMS - Sham Treatment | Rate of Change Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | day 2 mean | 23.54 units on a scale | Standard Error 1.53 |
| LFMS - Sham Treatment | Rate of Change Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | day 1 mean | 22.25 units on a scale | Standard Error 1.34 |
p-value: <0.182Regression, Linear
Secondary
Rate of of Change in Daily Improvement Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale
PANAS consists of 10 positive and 10 negative valence word items. Items are rated by the participant to indicate their assessment of how they are feeling about this item right now on a scale of 1(slightly) or not at all through 5 (extremely). 10 of of the items form a positive affect subscale, in which a higher score indicates increased positive affect, with a subscale range of 10 to 50. 10 of the items form a negative affect subscale, in which a higher score indicates more negative affect, with a subscale range of 10 to 50. This outcome measure uses the 10 item positive affect subscale. This outcome measure is the least squares fit of a linear coefficient to the three post (\<30min oost treatment) minus pre (\<30min pre treatment) score differences for the three treatment days
Time frame: Over 3 days of treatment
Population: Subjects completing 3 treatments and 1 visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFMS - Active Treatment | Rate of of Change in Daily Improvement Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | linear coefficient | -0.471 units on a scale | Standard Error 0.594 |
| LFMS - Active Treatment | Rate of of Change in Daily Improvement Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | day 1 mean | 0.50 units on a scale | Standard Error 1.14 |
| LFMS - Active Treatment | Rate of of Change in Daily Improvement Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | day 2 mean | -0.63 units on a scale | Standard Error 0.68 |
| LFMS - Active Treatment | Rate of of Change in Daily Improvement Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | day 3 mean | -0.44 units on a scale | Standard Error 0.65 |
| LFMS - Sham Treatment | Rate of of Change in Daily Improvement Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | day 3 mean | 0.65 units on a scale | Standard Error 0.77 |
| LFMS - Sham Treatment | Rate of of Change in Daily Improvement Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | linear coefficient | -0.375 units on a scale | Standard Error 0.648 |
| LFMS - Sham Treatment | Rate of of Change in Daily Improvement Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | day 2 mean | 0.21 units on a scale | Standard Error 0.91 |
| LFMS - Sham Treatment | Rate of of Change in Daily Improvement Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | day 1 mean | 1.40 units on a scale | Standard Error 1.09 |
p-value: <0.449Regression, Linear