Transcranial Direct Current Stimulation (tDCS) for Depression in Pregnancy: A Pilot Study

Study Overview
=================
Brief Summary
-----------------
The purpose of this pilot study is to examine the feasibility of conducting a multi-site double-blind randomized controlled trial whose aim will be to evaluate the effectiveness of transcranial direct current stimulation (tDCS) for treatment in pregnant women with moderate to severe major depression.

Detailed Description
-----------------
Major depression is a serious condition that affects up to 10% of pregnant women, and has serious impact on the developing fetus. However current treatments are less than ideal for women with moderate to severe depression. Psychotherapy alone is either ineffective, or takes months to improve symptoms, leaving the fetus susceptible to depression during that time. Antidepressant medication is effective, but there are high refusal rates of standard pharmacological treatment because of fears about medication exposure. The highly negative impacts of depression in pregnancy on the developing fetus and child illustrate the need for evaluation of timely and innovative treatments. Transcranial direct current stimulation (tDCS) is a non-drug treatment for depression where the dorsolateral prefrontal cortex, a part of the brain that functions abnormally when an individual is depressed, can be directly stimulated without impacting any other parts of the body or brain. As such, it is an ideal treatment for pregnant women who do not want to expose their fetus to the impact of medication treatment for depression. It has been shown to be effective in depression among non-pregnant adults and improvement is seen rapidly with a 3-week treatment course, almost 3 times faster than standard psychological treatment. There are no known serious adverse effects and no theoretical risk to a fetus. This research study will measure the feasibility, acceptability and compliance of the tDCS as a treatment option for depression in pregnancy. In addition, the study will investigate the effect of tDCS on reducing depressive symptoms immediately post-treatment among women who have moderate to severe depression in pregnancy. In this multi-centre, pilot randomized controlled trial, adult women with moderate to severe depression in pregnancy will be recruited from one hospital obstetrical group and two specialty perinatal mental health clinics over the course of 1 year. Women will have been offered to start or continue SSRI (Selective Serotonin Reuptake Inhibitors) or SNRI (Selective Serotonin-Norepinephrine Reuptake Inhibitors)medication but declined use. All participants will continue to receive clinical care from their respective clinical programs during the trial. Although this care may include psychotherapeutic intervention that is initiated prior to completion of the active tDCS treatment phase (if clinic psychotherapy waitlist is short), we would not expect to see improvement within the first 3 weeks of psychotherapeutic treatment. As such, this is an ideal opportunity to evaluate the efficacy of a new treatment, without depriving women of non-pharmacological standard care. Following informed consent procedures, participants will be randomized to tDCS or a sham-control condition (1:1) with on-site treatments 5 days per week over 3 weeks in 30 minute sessions. The intervention is active 2mA transcranial direct current stimulation (tDCS). Direct current will be transferred with a pair of saline soaked sponge electrodes (contact area 5 x 7cm), and delivered by a specially developed, battery driven constant current stimulator. The electrodes will be placed over F3 and F4 according to the international system for EEG (Electroencephalogram) placement. Sham stimulation will be administered using the same stimulation parameters and at the site of active treatment, but the current will be turned off after 30 seconds. Women will be interviewed at baseline and then followed during treatment, every four weeks until delivery, and at four and twelve weeks postpartum to allow for measurement of depressive symptoms, pregnancy, delivery, neonatal and infant outcomes. Although baseline and treatment interviews will be conducted in person, post-treatment and post-delivery interviews will be offered in person or over the telephone, according to participant preference.

Official Title
-----------------
Transcranial Direct Current Stimulation (tDCS) for Depression in Pregnancy: A Pilot Study

Conditions
-----------------
Depression, Pregnancy

Intervention / Treatment
-----------------
* Device: Active tDCS
* Device: Sham tDCS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pregnant women aged > 18 years >12 weeks gestation at enrollment 32 or fewer weeks gestation at first treatment visit (to increase likelihood of all treatment occurring during pregnancy) Diagnosis of Major Depressive Disorder and in a Moderate-severe major depressive episode without psychotic features (as confirmed by the Mini-International Neuropsychiatric Interview, MINI ). Safe for outpatient psychiatric treatment (as assessed by Study PI). Offered, but declined to use an anti-depressant medication Capable to consent to treatment Able to understand study explanations and have questionnaires administered in English Exclusion Criteria: DSM-V history of alcohol and/or substance use or dependence in the previous 6 months Concomitant major and unstable medical or neurologic illness or history of seizure Currently taking carbamazepine (which may interfere with the effects of anodal tDCS), Major complications and/or a known fetal anomaly in the current pregnancy as determined by the investigator team Planning to leave Toronto prior to delivery in the current pregnancy. Metal implant(s) in cranium Electrical implant(s) in body Currently taking benzodiazepines daily (Intermittent PRN use of low-dose Lorazepam allowed) Non-intact skin on scalp areas where stimulation electrodes will be placed History of very preterm delivery in previous pregnancy (< 32 weeks gestation)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active tDCS<br>The intervention is active 2mA transcranial direct current stimulation (tDCS). Direct current will be transferred with a pair of saline soaked sponge electrodes (contact area 5 x 7cm), and delivered for 30 minutes. The electrodes will be placed over F3 and F4 according to the 10-20 international system for EEG placement. | Device: Active tDCS<br>* The intervention is active 2mA transcranial direct current stimulation (tDCS). Direct current will be transferred with a pair of saline soaked sponge electrodes (contact area 5 x 7cm), and delivered for 30 minutes. The electrodes will be placed over F3 and F4 according to the 10-20 international system for EEG placement.<br>|
| Sham Comparator: Sham tDCS<br>The sham intervention is transcranial direct current stimulation (tDCS). 2mA of direct current will be transferred with a pair of saline soaked sponge electrodes (contact area 5 x 7cm), and the current will be turned off after 54 seconds.The electrodes will be placed over F3 and F4 according to the 10-20 international system for EEG placement. | Device: Sham tDCS<br>* The sham intervention is transcranial direct current stimulation (tDCS). 2mA of direct current will be transferred with a pair of saline soaked sponge electrodes (contact area 5 x 7cm), and the current will be turned off after 54 seconds.The electrodes will be placed over F3 and F4 according to the 10-20 international system for EEG placement.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants recruited over 1 year | Feasibility | Up to one year from when the study starts enrolling participants | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery Asberg Depression Rating Scale | Efficacy - Depression Symptom Measurement | End of week 1 | 
| Edinburgh Postnatal Depression Scale | Efficacy - Depression Symptom Measurement | End of Week 1 | 
| Pregnancy Experience Scale | Efficacy - Secondary Symptom Measurement | End of Week 1 | 
| State-Trait Anxiety Inventory | Efficacy - Secondary Symptom Measurement | End of week 1 | 
| Itemized neonatal health outcomes questionnaire | Neonatal outcome (safety) | 4 weeks postpartum | 
| Itemized neonatal health outcomes questionnaire | Neonatal Outcome (safety) | 12 weeks postpartum | 
| Bates Infant Characteristics Questionnaire | Infant outcome (temperament) | 12 weeks postpartum | 
| Ages and Stages Questionnaire | Infant outcome (development) | 12 weeks postpartum | 
| Toronto Side Effects Scale | Acceptability - side effects | End of Week 1 | 
| Toronto Side Effects Scale | Acceptability - side effects | End of week 2 | 
| Toronto Side Effects Scale | Acceptability - side effects | End of intervention phase (end of week 3) | 
| Itemized treatment acceptability questionnaire | Acceptability - barriers and facilitators of attending appointments | End of intervention phase (end of week 3) | 
| Pregnancy Complications Itemized Questionnaire |  | End of week 1 | 
| Pregnancy Complications Itemized Questionnaire |  | End of week 2 | 
| Pregnancy Complications Itemized Questionnaire |  | End of intervention phase (end of week 3) | 
| Pregnancy Complications Itemized Questionnaire |  | Every 4 weeks until delivery of baby (up to 26 weeks from initial randomization) | 
| Pregnancy Complications Itemized Questionnaire |  | 4 weeks postpartum | 
| Rate of follow-up data collection |  | 12 weeks postpartum | 
| Completion of all 15 treatment sessions |  | End of intervention phase (end of week 3) | 
| Treatment allocation questionnaire |  | End of week 1 | 
| Treatment allocation questionnaire |  | End of intervention phase (end of week 3) | 
| Montgomery Asberg Depression Rating Scale | Efficacy - Depression Symptom Measurement | End of week 2 | 
| Edinburgh Postnatal Depression Scale | Efficacy - Depression Symptom Measurement | End of Week 2 | 
| Montgomery Asberg Depression Rating Scale | Efficacy - Depression Symptom Measurement | End of intervention phase (End of week 3) | 
| Montgomery Asberg Depression Rating Scale | Efficacy - Depression Symptom Measurement | Every 4 weeks until delivery (i.e. up to 26 weeks from initial randomization) | 
| Montgomery Asberg Depression Rating Scale | Efficacy - Depression Symptom Measurement | 4 weeks postpartum | 
| Montgomery Asberg Depression Rating Scale | Efficacy - Depression Symptom Measurement | 12 weeks postpartum | 
| Edinburgh Postnatal Depression Scale | Efficacy - Depression Symptom Measurement | End of intervention phase (Week 3) | 
| Edinburgh Postnatal Depression Scale | Efficacy - Depression Symptom Measurement | Every 4 weeks until delivery (i.e. up to 26 weeks from initial randomization) | 
| Edinburgh Postnatal Depression Scale | Efficacy - Depression Symptom Measurement | 4 weeks postpartum | 
| Edinburgh Postnatal Depression Scale | Efficacy - Depression Symptom Measurement | 12 weeks postpartum | 
| Pregnancy Experience Scale | Efficacy - Secondary Symptom Measurement | End of Week 2 | 
| Pregnancy Experience Scale | Efficacy - Secondary Symptom Measurement | End of intervention phase (Week 3) | 
| Pregnancy Experience Scale | Efficacy - Secondary Symptom Measurement | Every 4 weeks until delivery (i.e. up to 26 weeks from initial randomization) | 
| State-Trait Anxiety Inventory | Efficacy - Secondary Symptom Measurement | End of week 2 | 
| State-Trait Anxiety Inventory | Efficacy - Secondary Symptom Measurement | End of intervention phase (end of week 3) | 
| State-Trait Anxiety Inventory | Efficacy - Secondary Symptom Measurement | Every 4 weeks until delivery (i.e. up to 26 weeks from initial randomization) | 
| State-Trait Anxiety Inventory | Efficacy - Secondary Symptom Measurement | 4 weeks postpartum | 
| State-Trait Anxiety Inventory | Efficacy - Secondary Symptom Measurement | 12 weeks postpartum | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Depression, Pregnancy, Transcranial Direct Current Stimulation