Major Depressive Disorder
Conditions
Keywords
non-invasive brain stimulation (NIBS), transcranial direct current stimulation (tDCS)
Brief summary
The investigators propose a study of telehealth supervised, caregiver-delivered, home-based transcranial direct current stimulation (tDCS) for antidepressant treatment of patients with an acute depressive episode.
Detailed description
This is an open-label pilot feasibility telemedicine study. This pilot will involve a total of 37 stimulations sessions / at home visits (30- minute sessions of multichannel excitatory tDCS targeting the left DPFC) and the maintenance of a daily treatment diary to be completed by the subjects immediately after enrollment and 12 weeks following the last study visit.
Interventions
DEVICEtDCS
Daily sessions (28 daily sessions): The device will be used to apply 30 minutes of tDCS to the participant with MDD's scalp in each of 28 daily sessions. Thereafter, participants with MDD will undergo a taper phase of an additional 9 sessions of tDCS applied in progressively decreasing frequency until day #60 of the study as follows: 1. First taper phase: three 30 minutes tDCS sessions applied every other day; 2. Second taper phase: three 30 minutes tDCS sessions applied one every third day; 3. Third and final taper phase: three final 30 minutes tDCS sessions applied one every fourth day.
Sponsors
Hebrew SeniorLife
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients meeting one of the following criteria may be eligible to participate in this study. 1. Patients with medication-resistant MDD who have undergone rTMS or ECT and responded to it but whose benefit has lapsed, and they need repeat a rTMS or ECT course that they cannot access 2. Patients with medication-resistant MDD who have undergone rTMS or ECT and responded to it but whose benefit has lapsed, and they need repeat a rTMS or ECT course that they cannot access 3. Patients with medication-resistant MDD who are undergoing rTMS or ECT and responding, but cannot continue to get the rTMS or ECT course due to COVID-19 pandemic-related regulations or other access concerns 4. Patients with medication-resistant MDD who are referred to rTMS or ECT and are found well qualified but cannot access rTMS or ECT due to COVID-19 pandemic-related regulations or other access concerns. The benefits of this project address a present need due to the COVID-19 pandemic, but also go beyond the present situation and address a larger, pre-existing need. Across all these potential groups of participants, prospective participants will: * need to have a primary psychiatrist who agrees to their participation in the study and is willing to continue to follow the patient and work collaboratively with the study team * need to be assessed by their primary psychiatrist to be stable enough to be able to remain at home and participate in the present study without undue risk to their safety * need to be living with an adult willing and capable to provide oversight and learn to deliver the home-based tDCS * have the capability to connect with the study team for daily supervision of the intervention sessions and close safety monitoring, and be willing to commit to doing so Inclusion Criteria: Individuals with MDD Participants will be men and women who: * Are aged 50 or older * Able to read, write, and communicate in English * Have a caregiver who is willing and able to provide the home tDCS sessions. * Participants must be under the care of a treating psychiatrist who approves of the study participation and believes that TMS or ECT is indicated for his/her patient but that * it would not endanger the patient to participate in the present study rather than pursue such alternative, or * the patient could not gain access to TMS or ECT due to COVID-19 (The depression phase of bi-polar disorder is not a reason for exclusion if the treating psychiatrist believes TMS or ECT would be indicated). Participants with MDD must fit into one of the following 3 groups (medication-resistant MDD defined as 1) participant's condition has not responded to prescribed antidepressant medication; 2) participant is medication intolerant, or 3) some other underlying reason): * Patients with medication-resistant Major depressive disorder (MDD) who have undergone repetitive transcranial magnetic stimulation (rTMS) or electroconvulsive therapy (ECT) and responded to it but whose benefit has lapsed and they need repeat rTMS or ECT course that they cannot access; * Patients with medication-resistant MDD who are undergoing rTMS or ECT and responding, but cannot continue to get the rTMS or ECT course due to COVID-19 pandemic-related regulations or other access concerns * Patients with medication-resistant MDD who are referred to rTMS or ECT and are found well qualified but cannot access rTMS or ECT due to COVID-19 pandemic-related regulations or other access concerns. Further, participants must: * Meet criteria for a diagnosis of MDD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) (American Psychiatric Association, 2000), as determined via an tele-health interview with a study psychiatrist, and confirmed with the Mini International Neuropsychiatric Interview (MINI; Version 5.0.0) (Sheehan et al., 1998) and the prospective participant's primary psychiatrist. * Currently experiencing a major depressive episode of at least four weeks' duration as part of a unipolar or bipolar depression. Score will need to be at least 20 on the MADRS. Further, participants must have a willing and eligible caregiver-administrators who is: * At least 21 years of age * Able to read, write, and communicate in English * Self-reported computer proficiency and willingness to learn how to use tDCS as defined by yes answers to the questions Do you feel comfortable using a computer? and are you willing to learn * How to administer tDCS? Stated availability throughout the study period to administer tDCS sessions to the participant with MDD.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale (MADRS) | 12 weeks | The MADRS is a 10-item clinical rating scale to measure the severity of depressive symptoms based on a clinical interview with a participant/patient. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60, and includes questions related to: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Cut off points are: 0 to 6 - normal, symptom absent, 7 to 19 - mild depression, 20 to 34 - moderate depression, \>34 - severe depression. Clinical remission is considered as a MADRS score ≤ 10. The primary outcome will be total MADRS score from baseline to one-month follow-up (pre and post-intervention; 12 weeks). |
| Number of Treatment-Emergent Adverse Events [Safety and Tolerability] and Missed Sessions | 12 weeks | Feasibility and tolerability/safety will be evaluated using home-based data as recorded in the Neuroelectrics portal: number of missed sessions and number of adverse events reported on adverse event questionnaire |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Beck Depression Inventory (BDI) | 12 weeks | The Beck Depression Inventory (BDI) is 21-item multiple-choice self-report inventory, one of the most widely used instruments for measuring the severity of depression. For each item, a value of 0 to 3 is assigned and then the total score is summed. The standard cut-offs are as follows: 0-9: indicates minimal depression 10-18: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression. Higher total scores indicate more severe depressive symptoms. This scale was given at baseline and 12 weeks later at the 1-month follow-up visit. |
| Hamilton Depression Rating Scale | 12 weeks | Hamilton Depression Rating Scale (HDRS) is comprised of 21 items for inquiry, and only the first 17 are used in scoring. Each question examines a different symptom or aspect of depression, including: mood, guilt, suicidal ideation, insomnia, agitation, and somatic symptoms. Items are scaled either from 0 - 2 or 0 - 4, and each item is summed for a total score. Benchmarks suggested at: 0-7 normal; 8 - 13 mild depression; 14-18 moderate depression; 19-22 severe depression ; \>=23 very severe depression. This scale was administered at baseline and 12 weeks later at the 1-month follow-up visit. |
| The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) | 12 weeks | The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) is a 16 item questionnaire that captures life satisfaction over the past week across several domains. Each question is rated on a 5 point scale from 1 (Very Poor) to 5 (Very Good). The Total Score is reported as percentage maximum possible % Max = Raw-minimum score/maximum score-minimum score. (Raw score minus the minimum possible raw score divided by the maximum possible raw score minus the minimum possible raw score). This measure was administered at baseline and at 1 month follow-up, which were separated by 12 weeks. |
| Digit Span Forward | 12 weeks | A digit-span forward task measures working memory storage capacity of numbers. Participants are auditorily presented with a chain of numerical digits and are instructed to recall the sequence of numbers verbally in the order that it was presented to the participant. The number of digits on the first trial is three. The length of the sequence increases with each correct trial completion. The more numbers recalled the better a participants has done. |
| Digit Span Backward | 12 weeks | A digit-span task backwards measures working memory storage capacity of numbers. Participants are auditorily presented with a chain of numerical digits and are instructed to recall the sequence of numbers verbally in backwards order. The number of digits on the first trial is two. The length of the sequence increases with each correct trial completion. The more numbers recalled the better a participants has done. |
| Montreal Cognitive Assessment (MoCA) | 12 weeks | The Montreal Cognitive Assessment (MoCA) is designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains. The total possible score is 30 points; a score of 26 or above is considered normal. Severity of impairment can be determined with the following scores: 18-25 = mild cognitive impairment, 10-17= moderate cognitive impairment, and less than 10= severe cognitive impairment. The maximum total score is 30 and the minimum total score is 0 points. This assessment was administered at baseline and at 1 month post-intervention (12 week span). |
| The Quick Inventory of Depressive Symptomatology (16-Item) (Self-Report)(QIDS-SR16) | 12 weeks | The Quick Inventory of Depressive Symptomatology (16-Item) (Self-Report)(QIDS-SR16) is a self-report measure of depressed symptomology. Questions in the QIDS - SR-16 correlate with the nine DSM-IV symptom criterion domains, Including: Sleep disturbance (initial, middle, and late insomnia or hypersomnia) (Q 1 - 4), Sad mood (Q 5), Decrease/increase in appetite/weight (Q 6 - 9), Concentration (Q 10), Self-criticism (Q 11), Suicidal ideation (Q 12), Interest (Q 13), Energy/fatigue (Q 14), Psychomotor agitation/retardation (Q 15 - 16). Severity of depression can be judged based on the total score, which ranges from 0 to 27. 1-5 = No depression 6-10 = Mild depression 11-15 = Moderate depression 16-20 = Severe depression 21-27 = Very severe depression This measure was administered at baseline and at 1 month follow-up, which were separated by 12 weeks. |
Countries
United States
Participant flow
Pre-assignment details
No significant events occurred between participant enrollment and start of the intervention.
Participants by arm
| Arm | Count |
|---|---|
| tDCS MDD A group of 5 participants with major depressive disorder (MDD).
tDCS, as a relatively simple and portable technology, is particularly well suited for remotely-supervised, home-based treatment, which would facilitate longer periods of treatment as well as offer a suitable therapeutic option at the present time as the investigators aim to deal with the COVID-19 pandemic.
tDCS: Daily sessions (28 daily sessions): The device will be used to apply 30 minutes of tDCS to the participant with MDD's scalp in each of 28 daily sessions.
Thereafter, participants with MDD will undergo a taper phase of an additional 9 sessions of tDCS applied in progressively decreasing frequency until day #60 of the study as follows:
1. First taper phase: three 30 minutes tDCS sessions applied every other day;
2. Second taper phase: three 30 minutes tDCS sessions applied one every third day;
3. Third and final taper phase: three final 30 minutes tDCS sessions applied one every fourth day. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Phase 1 - Acute Stimulation, Daily tDCS | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | tDCS MDD |
|---|---|
| Age, Continuous | 63.2 years STANDARD_DEVIATION 10.5 |
| Beck Depression Inventory (BDI) | 24.8 units on a scale |
| Digit Span Backward | 6 Count of numbers correctly recalled |
| Digit Span Forward | 7.6 Count of numbers correctly recalled |
| Hamilton Depression Rating Scale (HDRS) | 19.8 units on a scale |
| Montgomery-Asberg Depression Rating Scale (MADRS) | 35 units on a scale |
| Montreal Cognitive Assessment (MoCA) | 27.8 units on a scale |
| Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) | 33.2 units on a scale |
| Quick Inventory of Depressive Symptomatology (16-Item) (Self-Report)(QIDS-SR16) | 17.6 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Montgomery-Asberg Depression Rating Scale (MADRS)
The MADRS is a 10-item clinical rating scale to measure the severity of depressive symptoms based on a clinical interview with a participant/patient. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60, and includes questions related to: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Cut off points are: 0 to 6 - normal, symptom absent, 7 to 19 - mild depression, 20 to 34 - moderate depression, \>34 - severe depression. Clinical remission is considered as a MADRS score ≤ 10. The primary outcome will be total MADRS score from baseline to one-month follow-up (pre and post-intervention; 12 weeks).
Time frame: 12 weeks
Population: A group of participants with major depressive disorder (MDD).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| tDCS MDD | Montgomery-Asberg Depression Rating Scale (MADRS) | 16 units on a scale |
Primary
Number of Treatment-Emergent Adverse Events [Safety and Tolerability] and Missed Sessions
Feasibility and tolerability/safety will be evaluated using home-based data as recorded in the Neuroelectrics portal: number of missed sessions and number of adverse events reported on adverse event questionnaire
Time frame: 12 weeks
Population: A group of participants with major depressive disorder (MDD).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| tDCS MDD | Number of Treatment-Emergent Adverse Events [Safety and Tolerability] and Missed Sessions | Number of missed sessions | 1 number of sessions/events |
| tDCS MDD | Number of Treatment-Emergent Adverse Events [Safety and Tolerability] and Missed Sessions | Number of treatment-emergent adverse events | 0 number of sessions/events |
Secondary
Beck Depression Inventory (BDI)
The Beck Depression Inventory (BDI) is 21-item multiple-choice self-report inventory, one of the most widely used instruments for measuring the severity of depression. For each item, a value of 0 to 3 is assigned and then the total score is summed. The standard cut-offs are as follows: 0-9: indicates minimal depression 10-18: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression. Higher total scores indicate more severe depressive symptoms. This scale was given at baseline and 12 weeks later at the 1-month follow-up visit.
Time frame: 12 weeks
Population: A group of participants with major depressive disorder (MDD).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| tDCS MDD | Beck Depression Inventory (BDI) | 10.3333 units on a scale |
Secondary
Digit Span Backward
A digit-span task backwards measures working memory storage capacity of numbers. Participants are auditorily presented with a chain of numerical digits and are instructed to recall the sequence of numbers verbally in backwards order. The number of digits on the first trial is two. The length of the sequence increases with each correct trial completion. The more numbers recalled the better a participants has done.
Time frame: 12 weeks
Population: A group of participants with major depressive disorder (MDD).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| tDCS MDD | Digit Span Backward | 6 Count of numbers correctly recalled |
Secondary
Digit Span Forward
A digit-span forward task measures working memory storage capacity of numbers. Participants are auditorily presented with a chain of numerical digits and are instructed to recall the sequence of numbers verbally in the order that it was presented to the participant. The number of digits on the first trial is three. The length of the sequence increases with each correct trial completion. The more numbers recalled the better a participants has done.
Time frame: 12 weeks
Population: A group of participants with major depressive disorder (MDD).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| tDCS MDD | Digit Span Forward | 8 Count of numbers correctly recalled |
Secondary
Hamilton Depression Rating Scale
Hamilton Depression Rating Scale (HDRS) is comprised of 21 items for inquiry, and only the first 17 are used in scoring. Each question examines a different symptom or aspect of depression, including: mood, guilt, suicidal ideation, insomnia, agitation, and somatic symptoms. Items are scaled either from 0 - 2 or 0 - 4, and each item is summed for a total score. Benchmarks suggested at: 0-7 normal; 8 - 13 mild depression; 14-18 moderate depression; 19-22 severe depression ; \>=23 very severe depression. This scale was administered at baseline and 12 weeks later at the 1-month follow-up visit.
Time frame: 12 weeks
Population: A group of participants with major depressive disorder (MDD).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| tDCS MDD | Hamilton Depression Rating Scale | 7.3333 units on a scale |
Secondary
Montreal Cognitive Assessment (MoCA)
The Montreal Cognitive Assessment (MoCA) is designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains. The total possible score is 30 points; a score of 26 or above is considered normal. Severity of impairment can be determined with the following scores: 18-25 = mild cognitive impairment, 10-17= moderate cognitive impairment, and less than 10= severe cognitive impairment. The maximum total score is 30 and the minimum total score is 0 points. This assessment was administered at baseline and at 1 month post-intervention (12 week span).
Time frame: 12 weeks
Population: A group of participants with major depressive disorder (MDD).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| tDCS MDD | Montreal Cognitive Assessment (MoCA) | 28.6667 units on a scale |
Secondary
The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF)
The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) is a 16 item questionnaire that captures life satisfaction over the past week across several domains. Each question is rated on a 5 point scale from 1 (Very Poor) to 5 (Very Good). The Total Score is reported as percentage maximum possible % Max = Raw-minimum score/maximum score-minimum score. (Raw score minus the minimum possible raw score divided by the maximum possible raw score minus the minimum possible raw score). This measure was administered at baseline and at 1 month follow-up, which were separated by 12 weeks.
Time frame: 12 weeks
Population: A group of participants with Major Depressive Disorder (MDD).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| tDCS MDD | The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) | 44.6667 units on a scale |
Secondary
The Quick Inventory of Depressive Symptomatology (16-Item) (Self-Report)(QIDS-SR16)
The Quick Inventory of Depressive Symptomatology (16-Item) (Self-Report)(QIDS-SR16) is a self-report measure of depressed symptomology. Questions in the QIDS - SR-16 correlate with the nine DSM-IV symptom criterion domains, Including: Sleep disturbance (initial, middle, and late insomnia or hypersomnia) (Q 1 - 4), Sad mood (Q 5), Decrease/increase in appetite/weight (Q 6 - 9), Concentration (Q 10), Self-criticism (Q 11), Suicidal ideation (Q 12), Interest (Q 13), Energy/fatigue (Q 14), Psychomotor agitation/retardation (Q 15 - 16). Severity of depression can be judged based on the total score, which ranges from 0 to 27. 1-5 = No depression 6-10 = Mild depression 11-15 = Moderate depression 16-20 = Severe depression 21-27 = Very severe depression This measure was administered at baseline and at 1 month follow-up, which were separated by 12 weeks.
Time frame: 12 weeks
Population: A group of participants with major depressive disorder (MDD).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| tDCS MDD | The Quick Inventory of Depressive Symptomatology (16-Item) (Self-Report)(QIDS-SR16) | 5.3333 units on a scale |