Transcranial direct current stimulation (tDCS) for depression in pregnancy: A pilot randomized controlled trial
Introduction
Major depression affects up to 10% of pregnant women and is associated with adverse outcomes for mother and developing child [1]. These include negative impact on maternal well-being and quality of life, and poor neonatal outcomes such as preterm birth and problems with fetal growth and development [2]. Depression in pregnancy is the strongest predictor of postpartum depression (PPD), a condition linked to problems with maternal-child interactions and child motor, language and socioemotional development [2]. Standard depression treatments are not ideal for pregnant women. Psychotherapies require time to take effect, and are often ineffective for severe depression [3]. Antidepressants (e.g. selective serotonin reuptake inhibitors) can be effective within weeks, but fetal exposure may increase risk for adverse child outcomes [4]. Accordingly, acceptability of current treatments is low, likely contributing to undertreatment of depression in this population, where as few as 20% of patients receive adequate care for their illness [5].
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation treatment for depression that changes regional brain activity in the prefrontal cortex without impacting autonomic or thermoregulatory functions [6,7], thus posing no theoretical risk to a developing fetus when applied in pregnancy. A recent meta-analysis of 6 trials (289 non-pregnant patients with depression) found active tDCS superior to sham-control with response rates of 34% vs. 19%, remission rates of 23.1% vs. 12.7% [8] and no differences between groups in treatment acceptability or drop-out rate [9]. A systematic review of neurostimulation treatments for antenatal depression revealed no randomized controlled trials (RCTs) assessing the safety and efficacy of tDCS in pregnancy [10]. Herein, we report on the first RCT of tDCS for depression in pregnancy. The objective of the study was to assess the feasibility, acceptability and adherence to an RCT protocol for tDCS to treat depression in pregnancy.
Section snippets
Study design
Following informed consent, we randomized pregnant women to active tDCS or sham-control between October 2014 and December 2016. Follow-up was completed in July 2017.
Ethics statement
All authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. All procedures involving human participants were approved by the Research Ethics Boards at
Feasibility of recruitment, retention and protocol adherence
From 33 eligible participants, 20 (61%) consented and were randomized to tDCS (n = 10) or sham-control (n = 10) (Fig. 1). Reasons for non-participation included difficulty with the study time commitment, travel to the hospital and competing childcare responsibilities. Participants ranged in age from 26 to 43 years (mean 32.3, standard deviation 4.15), with a median gestational age at enrolment of 21 weeks (interquartile range 20–26 weeks). Most participants had recurrent depression, comorbid
Discussion
To our knowledge, this pilot trial is the first RCT of tDCS for depression in pregnancy. This study demonstrated feasibility of recruitment, adherence to protocol and acceptability of a clinical trial of tDCS as a treatment option for antenatal depression. While the trial was not powered to evaluate efficacy, preliminary estimates were promising with a difference between groups on the MADRS corresponding to more than double the minimal clinically important difference on this scale. Positive
Declaration of interests
In the past 5 years, Dr. Vigod has received research support from the Canadian Institutes of Health Research, Sick Kids Foundation and the Ontario Ministry of Health. She receives an honorarium from UpToDate for publications related to depression and antidepressant use in pregnancy. Dr. Daskalakis has received research and equipment in-kind support for investigator-initiated studies through Brainsway Inc and Magventure. Dr. Blumberger receives research support from the CIHR, Brain and Behavior
Funding
This work was jointly supported by SickKids Foundation and the Canadian Institutes of Health Research Institute for Child and Youth Health and Development (grant number NI14 020). The funders did not have any role in the study design, in the plan for the collection, management and analysis of data, in the writing of this paper, or in the decision to submit this paper for publication.
Author contribution
Concept and design: All authors.
Obtained funding: All authors.
Statistical analysis: Vigod.
Drafting of the manuscript: Vigod.
Critical revision of the manuscript for important intellectual content: All authors.
Data availability
Dr. Vigod had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Acknowledgements
We would like to acknowledge the contribution of the research obstetrical RN team who delivered the intervention at Sinai Health System, in Toronto, Ontario (Sherryl Hewko, Mary-Jean Martin, Kim Foshay, Cheryl Brush, and Maria Rocco). We would like to acknowledge members of the perinatal psychiatry program at Sinai Health System led by Dr. Ariel Dalfen and members of the Reproductive Life Stages Program at Women's College Hospital, in Toronto, Ontario, who assisted with recruitment activities.
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