Elsevier

Brain Stimulation

Volume 12, Issue 6, November–December 2019, Pages 1475-1483
Brain Stimulation

Transcranial direct current stimulation (tDCS) for depression in pregnancy: A pilot randomized controlled trial

https://doi.org/10.1016/j.brs.2019.06.019Get rights and content

Highlights

  • Evaluation of transcranial direct current stimulation (tDCS) for depression in pregnancy is feasible.

  • Views of treatment were positive with no adverse effects.

  • Results support proceeding to a definitive randomized controlled trial to evaluate tDCS for antenatal depression.

  • Preliminary efficacy estimates are encouraging with respect to the potential use of tDCS in this under-treated population.

Abstract

Background

Depression in pregnancy negatively affects maternal-child health. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation treatment for depression, has not been evaluated in pregnancy.

Objective

To conduct a pilot randomized controlled trial (RCT) to evaluate tDCS for antenatal depression.

Methods

In this pilot RCT in Toronto, Ontario (October 2014 to December 2016), adult pregnant women 14–32 weeks gestation with major depressive disorder who had declined antidepressant medication were considered for inclusion. Participants were randomly assigned 1:1 to tDCS or sham-control. Active tDCS comprised 30-min sessions of 2 mAmp direct current delivered over the dorsolateral prefrontal cortex, 5 days per week, for 3 weeks. Sham was administered similarly, but with current turned off after 30 s. Main outcomes were feasibility, acceptability, and protocol adherence. Maternal Montgomery Asperg Depression Rating Scale (MADRS) was measured post-treatment and at 4 and 12 weeks postpartum.

Results

Of 20 women randomized, 16 completed treatment and provided data (124 tDCS, 122 sham sessions). Views of treatment were positive with no serious adverse events. Post-treatment estimated marginal mean MADRS scores were 11.8 (standard error, SE 2.66) for tDCS and 15.4 (SE 2.51) for sham (p = 0.34). At 4 weeks postpartum, 75.0% of tDCS women were remitted versus 12.5% sham-control (p = 0.04).

Conclusions

Results support proceeding to a definitive RCT to evaluate tDCS for antenatal depression. The preliminary efficacy estimates immediately post-treatment and in the postpartum, are encouraging with respect to the potential use of tDCS to improve treatment rates in this population. The trial was registered at: clinical trials.gov (NCT02116127).

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.

References (43)

  • D. Bennabi et al.

    Pilot study of feasibility of the effect of treatment with tDCS in patients suffering from treatment-resistant depression treated with escitalopram

    Clin Neurophysiol

    (2015)
  • N. Rotem-Kohavi et al.

    Alterations in resting-state networks following in utero selective serotonin reuptake inhibitor exposure in the neonatal brain

    Biol Psychiatry Cogn Neurosci Neuroimaging

    (2019)
  • C. Fonteneau et al.

    Sham tDCS: a hidden source of variability? Reflections for further blinded, controlled trials

    Brain Stimul

    (2019)
  • (CANMAT) CPAatCNfMaAT

    Clinical guidelines for the treatment of depressive disorders

    Can J Psychiatr

    (2001)
  • S.N. Vigod et al.

    Depression in pregnancy

    BMJ

    (2016)
  • N. Byatt et al.

    Mental health care use in relation to depressive symptoms among pregnant women in the USA

    Arch Womens Ment Health

    (2016)
  • A.R. Brunoni et al.

    Transcranial direct current stimulation for acute major depressive episodes: meta-analysis of individual patient data

    Br J Psychiatry

    (2016)
  • D.R. Kim et al.

    Neuromodulation and antenatal depression: a review

    Neuropsychiatric Dis Treat

    (2015)
  • S. Vigod et al.

    Transcranial direct current stimulation (tDCS) for treatment of major depression during pregnancy: study protocol for a pilot randomized controlled trial

    Trials

    (2014)
  • D.M. Blumberger et al.

    A randomized double-blind sham-controlled study of transcranial direct current stimulation for treatment-resistant major depression

    Front Psychiatry

    (2012)
  • A.R. Brunoni et al.

    The sertraline vs. electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial

    JAMA Psychiatry

    (2013)
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