RCT of At-Home tDCS for Depression in Pregnancy

Study Overview
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Brief Summary
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This is a randomized, sham-controlled trial to determine whether treatment with transcranial direct current stimulation (tDCS) is superior to a sham condition at reducing the symptoms of depression in pregnant people with moderate to severe depression. The study aims to enrol 156 participants across all sites. Data collection occurs at baseline, immediately after treatment, every 4 weeks during pregnancy and 4-, 12-, 26- and 52-weeks postpartum

Detailed Description
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Transcranial direct current stimulation (tDCS) is a brain stimulation technique for the treatment of depression that has great potential for filling the gap in treatment options for moderate and severe depression in pregnancy. Participants are randomized 1:1 to active tDCS treatment or sham control. After at least one in-person training session with the research team, participants take the tDCS device home and self-administer 30-minute treatments 5 times per week, for 3 weeks, for a total of 15 sessions. Rater-administered and self-report outcomes are collected weekly during the 3-week active treatment phase, every 4 weeks during pregnancy, and at 4-, 12-, 26- and 52-weeks postpartum. A mixed methods process evaluation is embedded into the trial.

Official Title
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Randomized Controlled Trial of At-home Transcranial Direct Current Stimulation (tDCS) for Depression in Pregnancy

Conditions
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Pregnancy, Major Depression, Postpartum Depression

Intervention / Treatment
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* Device: active tDCS
* Other: workbook
* Device: sham tDCS


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Adult, ≥18 years of age Singleton pregnancy, 12 to end of 32 weeks single gestation at randomization In a major depressive episode (MDE) with at least moderate symptom severity (PHQ-9 ≥10 and confirmed using MINI International Neuropsychiatric Interview as MDE without psychotic features) Assessed by a psychiatrist at one of the study recruitment sites during pregnancy, and offered the option of antidepressant medication for treatment but declined to use No new treatments for depression (i.e. psychological or somatic) and no pharmacological treatment for depression in the 4 weeks prior to starting treatment Exclusion criteria: Active alcohol or substance use disorder in previous 12 months as assessed by GAIN-SS Active suicidality as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Bipolar disorder as assessed by MINI International Neuropsychiatric Interview Schizophrenia or other psychotic disorder as assessed by MINI International Neuropsychiatric Interview Major unstable or life-threatening medical illness (e.g. such as advanced cancer), pre-eclampsia/eclampsia in current pregnancy or neurologic illness or seizure history Major congenital anomalies or major obstetrical complications in current pregnancy (determined by clinical PI/Co-I assessment) Metal implants in cranium or any electrical implants Benzodiazepine (except intermittent low-dose lorazepam no more than 2mg equivalent per day) or anticonvulsant use as these interfere with anodal tDCS Visibly non-intact skin/rash on scalp areas at stimulation electrode sites Unable to consent or complete study measures in English, or unable to complete depression in pregnancy workbook (the attention-control) in French or English

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: active tDCS<br>2mA of direct current delivered to the dorsolateral prefrontal cortex for 30 minutes each, 5 times per week for 3 weeks, for a total of 15 sessions using the Soterix Medical tDCS mini-CT model 1601-LTE. | Device: active tDCS<br>* 2mA of direct current delivered in 15 sessions lasting 30 minutes each over 3 weeks<br>Other: workbook<br>* Self-directed depression in pregnancy workbook completed during each session to control the in-session brain state<br>|
| Sham Comparator: control<br>Sham stimulation where the current is turned off after 30 seconds in a slow ramp down, delivered to the dorsolateral prefrontal cortex for 30 minutes each, 5 times per week for 3 weeks, for a total of 15 sessions using the Soterix Medical tDCS mini-CT model 1601-LTE. | Other: workbook<br>* Self-directed depression in pregnancy workbook completed during each session to control the in-session brain state<br>Device: sham tDCS<br>* Sham stimulation in which the current turns off after 30 seconds in a slow ramp down that mirrors sensory adaptation in ongoing stimulation, delivered in 15 sessions lasting 30 minutes each over 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depressive symptoms post treatment | Depressive symptoms are measured with the 10-item rater-administered Montgomery Asberg Depression Rating Scale (MADRS).The MADRS is a standard rater-administered measure with good reliability and validity in clinical populations; interviewers can achieve and maintain high levels of inter-rater reliability. Nine items are based upon patient report and one on rater observation. Items are rated on a 0-6 continuum (0=no abnormality, 6=severe; score range 0-60). A MADRS score of <11 indicates remission | End of Week 3 of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission of depression | Measured with the 10-item rater-administered Montgomery Asberg Depression Rating Scale (MADRS).The MADRS is a standard rater-administered measure with good reliability and validity in clinical populations; interviewers can achieve and maintain high levels of inter-rater reliability. Nine items are based upon patient report and one on rater observation. Items are rated on a 0-6 continuum (0=no abnormality, 6=severe; score range 0-60). A MADRS score of <11 indicates remission | 4 weeks postpartum | 
| Depressive symptoms | measured with the 10-item rater-administered Montgomery Asberg Depression Rating Scale (MADRS).The MADRS is a standard rater-administered measure with good reliability and validity in clinical populations; interviewers can achieve and maintain high levels of inter-rater reliability. Nine items are based upon patient report and one on rater observation. Items are rated on a 0-6 continuum (0=no abnormality, 6=severe; score range 0-60). A lower score indicates less severe symptoms. | End of Week 1, and Week 2 of treatment, q4 weeks during pregnancy, and 4-, 12-, 26- and 52-weeks postpartum | 
| Self-reported depressive symptoms | Depressive symptoms will be measured using the Edinburgh Postnatal Depressive Scale (EPDS), a self-report scale that has been validated for use in pregnancy and postpartum. EPDS scores range from 0 to 30. EPDS scores >12 are predictive of a diagnosis of depression, with higher scores indicating more severe symptoms | End of Week 1, Week 2 and Week 3 of treatment, q4 weeks during pregnancy (up to 28 weeks), and 4-, 12-, 26- and 52-weeks postpartum (up to 80 weeks) | 
| Self-reported anxiety symptoms | Measured using the Generalized Anxiety Disorder-7 (GAD-7) scale which is a self-report scale with good discriminate validity in perinatal populations. GAD-7 scores range from 0 to 21, with higher scores indicating more severe symptoms | End of Week 1, Week 2 and Week 3 of treatment, q4 weeks during pregnancy (up to 28 weeks), and 4-, 12-, 26- and 52-weeks postpartum (up to 80 weeks) | 
| Maternal Quality of Life (QoL) | Measured using 12-Item Short Form Survey (SF-12), a 12-item measure often used to estimate quality-adjusted life year (QALY), a preference-based utility measure of health-related QoL as perceived by the patient and the gold standard measure of effectiveness recommended for economic evaluation. SF12 scores consist of Physical and Mental Component Summaries. Scores range from 0-100 with higher scores indicating better functioning | End of Week 1, Week 2 and Week 3 of treatment, q4 weeks during pregnancy (up to 28 weeks), and 4-, 12-, 26- and 52-weeks postpartum (up to 80 weeks) | 
| Health Service Use: Health System Costs | Calculated from participant self-report of medical costs such as hospitalization, visits with health professionals and medications | End of Week 3 of treatment, q4 weeks during pregnancy (up to 28 weeks), and 4-, 12-, 26- and 52-weeks postpartum (up to 80 weeks) | 
| Health Service Use: Productivity Loss | Calculated from participant self-report of activities and time commitment related to attending appointments and obtaining services, work absences of the patient and family members | End of Week 3 of treatment, q4 weeks during pregnancy (up to 28 weeks), and 4-, 12-, 26- and 52-weeks postpartum (up to 80 weeks) | 
| Health Service Use: Participant Cost | Calculated from participant self-report of costs related to attending appointments and obtaining services | End of Week 3 of treatment, q4 weeks during pregnancy (up to 28 weeks), and 4-, 12-, 26- and 52-weeks postpartum (up to 80 weeks) | 
| Dyadic Relationship | Relationship satisfaction measured using the Dyadic Consensus Subscale, a 13-item subscale of the 32-item Dyadic Adjustment Scale (DAS). This self-report measure of the extent of agreement between partners is valid for measuring overall dyadic adjustment. Higher scores indicate a higher degree of dyadic consensus | End of Week 3 of treatment, q4 weeks during pregnancy (up to 28 weeks), and 4-, 12-, 26- and 52-weeks postpartum (up to 80 weeks) | 
| Maternal Birth Outcomes | Self-reported pregnancy and birth complications querying indicators recommended by the Canadian Perinatal Surveillance System (CPSS) | End of Week 1, Week 2 and Week 3 of treatment, q4 weeks during pregnancy (up to 28 weeks), and 4 weeks postpartum (up to 32 weeks) | 
| Neonatal Birth Outcomes | Self-reported neonatal birth outcomes including medical conditions and complications querying indicators recommended by the Canadian Perinatal Surveillance System (CPSS) | 4 weeks postpartum (up to 32 weeks) | 
| Maternal Child Relationship | Parenting stress is measured by the Parenting Stress Index Short Form (PSI-SF) which is a 36-item measure consisting of 6 sub-scales: parental distress, dysfunction in the parent-child relations and difficult child. Scores range from 36 to 180. Higher scores indicate higher levels of parenting stress | 4-, 12-, 26- and 52-weeks postpartum (up to 80 weeks) | 
| Infant Temperament | Measured using the Infant Characteristics Questionnaire (ICQ). The ICQ is a 27-item questionnaire with each item coded 1-7. Higher scores indicate higher parental perceptions of difficult infant temperament | 12 and 52 weeks postpartum (up to 80 weeks) | 
| Child Development | Assessed using the Ages and Stages Questionnaire (ASQ-3), a 30-item instrument that screens for child development from 1 to 60 months | 12 and 52 weeks postpartum (up to 80 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pregnancy, Depression, Transcranial direct current stimulation