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

Simone Vigod, Cindy-Lee Dennis, Zafiris Daskalakis, Kellie Murphy, Joel Ray, Tim Oberlander, Sarah Somerton, Neesha Hussain-Shamsy, Daniel Blumberger, Simone Vigod, Cindy-Lee Dennis, Zafiris Daskalakis, Kellie Murphy, Joel Ray, Tim Oberlander, Sarah Somerton, Neesha Hussain-Shamsy, Daniel Blumberger

Abstract

Background: Women with depression in pregnancy are faced with difficult treatment decisions. Untreated, antenatal depression has serious negative implications for mothers and children. While antidepressant drug treatment is likely to improve depressive symptoms, it crosses the placenta and may pose risks to the unborn child. Transcranial direct current stimulation is a focal brain stimulation treatment that improves depressive symptoms within 3 weeks of treatment by inducing changes to brain areas involved in depression, without impacting any other brain areas, and without inducing changes to heart rate, blood pressure or core body temperature. The localized nature of transcranial direct current stimulation makes it an ideal therapeutic approach for treating depression during pregnancy, although it has never previously been evaluated in this population.

Methods/design: We describe a pilot randomized controlled trial of transcranial direct current stimulation among women with depression in pregnancy to assess the feasibility of a larger, multicentre efficacy study. Women over 18 years of age and between 14 and 32 weeks gestation can be enrolled in the study provided they meet diagnostic criteria for a major depressive episode of at least moderate severity and have been offered but refused antidepressant medication. Participants are randomized to receive active transcranial direct current stimulation or a sham condition that is administered in 15 30-minute treatments over three weeks. Women sit upright during treatment and receive obstetrical monitoring prior to, during and after each treatment session. Depressive symptoms, treatment acceptability, and pregnancy outcomes are assessed at baseline (prior to randomization), at the end of each treatment week, every four weeks post-treatment until delivery, and at 4 and 12 weeks postpartum.

Discussion: Transcranial direct current stimulation is a novel therapeutic option for treating depression during pregnancy. This protocol allows for assessment of the feasibility of, acceptability of and adherence with a clinical trial protocol to administer this treatment to pregnant women with moderate to severe depression. Results from this pilot study will guide the development of a larger multicentre trial to definitively test the efficacy and safety of transcranial direct current stimulation for pregnant women with depression.

Trial registration: Clinical Trials Gov NCT02116127.

Figures

Figure 1
Figure 1
Trial design. Randomization schema of a pilot randomized controlled trial on the feasibility of transcranial direct current stimulation to treat depression during pregnancy. MADRS, Montgomery Asberg Depression Rating Scale; tDCS, transcranial direct brain stimulation.

References

    1. Bennett HA, Einarson A, Taddio A, Koren G, Einarson TR. Prevalence of depression during pregnancy: systematic review. Obstet Gynecol. 2004;103(4):698–709. doi: 10.1097/01.AOG.0000116689.75396.5f.
    1. Michaud CM, Murray CJ, Bloom BR. Burden of disease - implications for future research. JAMA. 2001;285(5):535–539. doi: 10.1001/jama.285.5.535.
    1. Wisner KL, Sit DK, Hanusa BH, Moses-Kolko EL, Bogen DL, Hunker DF, Perel JM, Jones-Ivy S, Bodnar LM, Singer LT. Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes. Am J Psychiatry. 2009;166(5):557–566. doi: 10.1176/appi.ajp.2008.08081170.
    1. Marcus SM. Depression during pregnancy: rates, risks and consequences - Motherisk update 2008. Can J Clin Pharmacol. 2009;16(1):e15–e22.
    1. Canadian Psychiatric Association; Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the treatment of depressive disorders. Can J Psychiatry. 2001;46(Suppl 1):1S–91S.
    1. Thase ME, Larsen KG, Kennedy SH. Assessing the ‘true’ effect of active antidepressant therapy v. placebo in major depressive disorder: use of a mixture model. Br J Psychiatry. 2011;199(6):501–507. doi: 10.1192/bjp.bp.111.093336.
    1. Chambers CD, Hernandez-Diaz S, Van Marter LJ, Werler MM, Louik C, Jones KL, Mitchell AA. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Engl J Med. 2006;354(6):579–587. doi: 10.1056/NEJMoa052744.
    1. Wen SW, Yang Q, Garner P, Fraser W, Olatunbosun O, Nimrod C, Walker M. Selective serotonin reuptake inhibitors and adverse pregnancy outcomes. Am J Obstet Gynecol. 2006;194(4):961–966. doi: 10.1016/j.ajog.2006.02.019.
    1. Casper RC, Fleisher BE, Lee-Ancajas JC, Gilles A, Gaylor E, DeBattista A, Hoyme HE. Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy. J Pediatr. 2003;142(4):402–408. doi: 10.1067/mpd.2003.139.
    1. Chambers CD, Johnson KA, Dick LM, Felix RJ, Jones KL. Birth outcomes in pregnant women taking fluoxetine. N Engl J Med. 1996;335(14):1010–1015. doi: 10.1056/NEJM199610033351402.
    1. Cohen LS, Heller VL, Bailey JW, Grush L, Ablon JS, Bouffard SM. Birth outcomes following prenatal exposure to fluoxetine. Biol Psychiatry. 2000;48(10):996–1000. doi: 10.1016/S0006-3223(00)00877-5.
    1. Costei AM, Kozer E, Ho T, Ito S, Koren G. Perinatal outcome following third trimester exposure to paroxetine. Arch Pediatr Adolesc Med. 2002;156(11):1129–1132. doi: 10.1001/archpedi.156.11.1129.
    1. Ericson A, Kallen B, Wiholm B. Delivery outcome after the use of antidepressants in early pregnancy. Eur J Clin Pharmacol. 1999;55(7):503–508. doi: 10.1007/s002280050664.
    1. Kulin NA, Pastuszak A, Sage SR, Schick-Boschetto B, Spivey G, Feldkamp M, Ormond K, Matsui D, Stein-Schechman AK, Cook L, Brochu J, Rieder M, Koren G. Pregnancy outcome following maternal use of the new selective serotonin reuptake inhibitors: a prospective controlled multicenter study. JAMA. 1998;279(8):609–610. doi: 10.1001/jama.279.8.609.
    1. Laine K, Heikkinen T, Ekblad U, Kero P. Effects of exposure to selective serotonin reuptake inhibitors during pregnancy on serotonergic symptoms in newborns and cord blood monoamine and prolactin concentrations. Arch Gen Psychiatry. 2003;60(7):720–726. doi: 10.1001/archpsyc.60.7.720.
    1. Levinson-Castiel R, Merlob P, Linder N, Sirota L, Klinger G. Neonatal abstinence syndrome after in utero exposure to selective serotonin reuptake inhibitors in term infants. Arch Pediatr Adolesc Med. 2006;160(2):173–176. doi: 10.1001/archpedi.160.2.173.
    1. Nordeng H, Lindemann R, Perminov KV, Reikvam A. Neonatal withdrawal syndrome after in utero exposure to selective serotonin reuptake inhibitors. Acta Paediatr. 2001;90(3):288–291. doi: 10.1080/080352501300067596.
    1. Oberlander TF, Eckstein Grunau R, Fitzgerald C, Ellwood AL, Misri S, Rurak D, Riggs KW. Prolonged prenatal psychotropic medication exposure alters neonatal acute pain response. Pediatr Res. 2002;51(4):443–453. doi: 10.1203/00006450-200204000-00008.
    1. Pastuszak A, Schick-Boschetto B, Zuber C, Feldkamp M, Pinelli M, Sihn S, Donnenfeld A, McCormack M, Leen-Mitchell M, Woodland C, Gardner A, Horn M, Koren G. Pregnancy outcome following first-trimester exposure to fluoxetine (Prozac) JAMA. 1993;269(17):2246–2248. doi: 10.1001/jama.1993.03500170076037.
    1. Simon GE, Cunningham ML, Davis RL. Outcomes of prenatal antidepressant exposure. Am J Psychiatry. 2002;159(12):2055–2061. doi: 10.1176/appi.ajp.159.12.2055.
    1. Stiskal JA, Kulin N, Koren G, Ho T, Ito S. Neonatal paroxetine withdrawal syndrome. Arch Dis Child Fetal Neonatal Ed. 2001;84(2):F134–F135. doi: 10.1136/fn.84.2.F134.
    1. Mulder EJ, Ververs FF, de Heus R, Visser GH. Selective serotonin reuptake inhibitors affect neurobehavioral development in the human fetus. Neuropsychopharmacology. 2011;36(10):1961–1971. doi: 10.1038/npp.2011.67.
    1. Fitzgerald PB, Brown TL, Marston NA, Daskalakis ZJ, De Castella A, Kulkarni J. Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial. Arch Gen Psychiatry. 2003;60(10):1002–1008.
    1. George MS, Ketter TA, Post RM. Prefrontal cortex dysfunction in clinical depression. Depression. 1994;2(2):59–72. doi: 10.1002/depr.3050020202.
    1. Speer AM, Kimbrell TA, Wassermann EM, Repella JD, Willis MW, Herscovitch P, Post RM. Opposite effects of high and low frequency rTMS on regional brain activity in depressed patients. Biol Psychiatry. 2000;48(12):1133–1141. doi: 10.1016/S0006-3223(00)01065-9.
    1. Ardolino G, Bossi B, Barbieri S, Priori A. Non-synaptic mechanisms underlie the after-effects of cathodal transcutaneous direct current stimulation of the human brain. J Physiol. 2005;568(2):653–663. doi: 10.1113/jphysiol.2005.088310.
    1. Miranda PC, Lomarev M, Hallett M. Modeling the current distribution during transcranial direct current stimulation. Clin Neurophysiol. 2006;117(7):1623–1629. doi: 10.1016/j.clinph.2006.04.009.
    1. Merzagora AC, Foffani G, Panyavin I, Mordillo-Mateos L, Aguilar J, Onaral B, Oliviero A. Prefrontal hemodynamic changes produced by anodal direct current stimulation. Neuroimage. 2010;49(3):2304–2310. doi: 10.1016/j.neuroimage.2009.10.044.
    1. Kalu UG, Sexton CE, Loo CK, Ebmeier KP. Transcranial direct current stimulation in the treatment of major depression: a meta-analysis. Psychol Med. 2012;42(9):1791–1800. doi: 10.1017/S0033291711003059.
    1. Loo CK, Alonzo A, Martin D, Mitchell PB, Galvez V, Sachdev P. Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial. Br J Psychiatry. 2012;200(1):52–59. doi: 10.1192/bjp.bp.111.097634.
    1. Boggio PS, Castro LO, Savagim EA, Braite R, Cruz VC, Rocha RR, Rigonatti SP, Silva MT, Fregni F. Enhancement of non-dominant hand motor function by anodal transcranial direct current stimulation. Neurosci Lett. 2006;404(1–2):232–236. doi: 10.1016/j.neulet.2006.05.051.
    1. Fregni F, Boggio PS, Lima MC, Ferreira MJ, Wagner T, Rigonatti SP, Castro AW, Souza DR, Riberto M, Freedman SD, Nitsche MA, Pascual-Leone A. A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. Pain. 2006;122(1–2):197–209. doi: 10.1016/j.pain.2006.02.023.
    1. Fregni F, Boggio PS, Mansur CG, Wagner T, Ferreira MJ, Lima MC, Rigonatti SP, Marcolin MA, Freedman SD, Nitsche MA, Pascual-Leone A. Transcranial direct current stimulation of the unaffected hemisphere in stroke patients. Neuroreport. 2005;16(14):1551–1555. doi: 10.1097/01.wnr.0000177010.44602.5e.
    1. Fregni F, Boggio PS, Nitsche M, Bermpohl F, Antal A, Feredoes E, Marcolin MA, Rigonatti SP, Silva MT, Paulus W, Pascual-Leone A. Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory. Exp Brain Res. 2005;166(1):23–30. doi: 10.1007/s00221-005-2334-6.
    1. Fregni F, Boggio PS, Nitsche MA, Marcolin MA, Rigonatti SP, Pascual-Leone A. Treatment of major depression with transcranial direct current stimulation. Bipolar Disord. 2006;8(2):203–204. doi: 10.1111/j.1399-5618.2006.00291.x.
    1. Lang N, Nitsche MA, Paulus W, Rothwell JC, Lemon RN. Effects of transcranial direct current stimulation over the human motor cortex on corticospinal and transcallosal excitability. Exp Brain Res. 2004;156(4):439–443. doi: 10.1007/s00221-003-1800-2.
    1. Nitsche MA, Liebetanz D, Lang N, Antal A, Tergau F, Paulus W. Safety criteria for transcranial direct current stimulation (tDCS) in humans. Clin Neurophysiol. 2003;114(11):2220–2222. doi: 10.1016/S1388-2457(03)00235-9.
    1. Nitsche MA, Boggio PS, Fregni F, Pascual-Leone A. Treatment of depression with transcranial direct current stimulation (tDCS): a review. Exp Neurol. 2009;219(1):14–19. doi: 10.1016/j.expneurol.2009.03.038.
    1. Poreisz C, Boros K, Antal A, Paulus W. Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients. Brain Res Bull. 2007;72(4–6):208–214. doi: 10.1016/j.brainresbull.2007.01.004.
    1. Raimundo RJ, Uribe CE, Brasil-Neto JP. Lack of clinically detectable acute changes on autonomic or thermoregulatory functions in healthy subjects after transcranial direct current stimulation (tDCS) Brain Stimul. 2012;5(3):196–200. doi: 10.1016/j.brs.2011.03.009.
    1. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59(Suppl 20):22–33.
    1. Ellish NJ, Saboda K, O’Connor J, Nasca PC, Stanek EJ, Boyle C. A prospective study of early pregnancy loss. Hum Reprod. 1996;11(2):406–412. doi: 10.1093/HUMREP/11.2.406.
    1. Kelly RH, Russo J, Holt VL, Danielsen BH, Zatzick DF, Walker E, Katon W. Psychiatric and substance use disorders as risk factors for low birth weight and preterm delivery. Obstet Gynecol. 2002;100(2):297–304. doi: 10.1016/S0029-7844(02)02014-8.
    1. Patel SR, Wisner KL. Decision making for depression treatment during pregnancy and the postpartum period. Depress Anxiety. 2011;28(7):589–595. doi: 10.1002/da.20844.
    1. Blumberger DM, Tran LC, Fitzgerald PB, Hoy KE, Daskalakis ZJ. A randomized double-blind sham-controlled study of transcranial direct current stimulation for treatment-resistant major depression. Front Psychiatry. 2012;3:74. doi: 10.3389/fpsyt.2012.00074.
    1. Brunoni AR, Valiengo L, Baccaro A, Zanao TA, de Oliveira JF, Vieira GP, Bueno VF, Goulart AC, Boggio PS, Lotufo PA, Bensenor IM, Fregni F. Sertraline vs. ELectrical Current Therapy for Treating Depression Clinical Trial–SELECT TDCS: design, rationale and objectives. Contemp Clin Trials. 2011;32(1):90–98. doi: 10.1016/j.cct.2010.09.007.
    1. Brunoni AR, Vanderhasselt MA, Boggio PS, Fregni F, Dantas EM, Mill JG, Lotufo PA, Benseñor IM. Polarity- and valence-dependent effects of prefrontal transcranial direct current stimulation on heart rate variability and salivary cortisol. Psychoneuroendocrinology. 2013;38(1):58–66. doi: 10.1016/j.psyneuen.2012.04.020.
    1. Herwig U, Padberg F, Unger J, Spitzer M, Schönfeldt-Lecuona C. Transcranial magnetic stimulation in therapy studies: examination of the reliability of ‘standard’ coil positioning by neuronavigation. Biol Psychiatry. 2001;50(1):58–61. doi: 10.1016/S0006-3223(01)01153-2.
    1. Vanderkooy JD, Kennedy SH, Bagby RM. Antidepressant side effects in depression patients treated in a naturalistic setting: a study of bupropion, moclobemide, paroxetine, sertraline, and venlafaxine. Can J Psychiatry. 2002;47(2):174–180.
    1. Demissie K, Joseph KS, Dzakpasu S. Perinatal Health Indicators for Canada: A Resource Manual. Ottawa, ON: Health Canada; 2000.
    1. Bates JE, Freeland CA, Lounsbury ML. Measurement of infant difficultness. Child Dev. 1979;50(3):794–803. doi: 10.2307/1128946.
    1. Bricker D, Squires J. Ages and Stages Questionnaire. 3. Baltimore, MD: Brookes Publishing; 2010.
    1. Schonhaut L, Armijo I, Schönstedt M, Alvarez J, Cordero M. Validity of the ages and stages questionnaires in term and preterm infants. Pediatrics. 2013;131(5):e1468–e1474. doi: 10.1542/peds.2012-3313.
    1. Hermens ML, Adèr HJ, van Hout HP, Terluin B, van Dyck R, de Haan M. Administering the MADRS by telephone or face-to-face: a validity study. Ann Gen Psychiatry. 2006;5:3. doi: 10.1186/1744-859X-5-3.
    1. Kjaergaard M, Arfwedson Wang CE, Waterloo K, Jorde R. A study of the psychometric properties of the Beck depression Inventory-II, the montgomery and Asberg depression rating scale, and the hospital anxiety and depression scale in a sample from a healthy population. Scand J Psychol. 2014;55(1):83–89. doi: 10.1111/sjop.12090.
    1. Gibson J, McKenzie-McHarg K, Shakespeare J, Price J, Gray R. A systematic review of studies validating the Edinburgh Postnatal Depression Scale in antepartum and postpartum women. Acta Psychiatr Scand. 2009;119(5):350–364. doi: 10.1111/j.1600-0447.2009.01363.x.
    1. Boyd RC, Le HN, Somberg R. Review of screening instruments for postpartum depression. Arch Womens Ment Health. 2005;8(3):141–153. doi: 10.1007/s00737-005-0096-6.
    1. Eberhard-Gran M, Eskild A, Tambs K, Opjordsmoen S, Samuelsen SO. Review of validation studies of the Edinburgh postnatal depression scale. Acta Psychiatr Scand. 2001;104(4):243–249. doi: 10.1034/j.1600-0447.2001.00187.x.
    1. DiPietro JA, Ghera MM, Costigan K, Hawkins M. Measuring the ups and downs of pregnancy stress. J Psychosom Obstet Gynaecol. 2004;25(3–4):189–201. doi: 10.1080/01674820400017830.
    1. Dennis CL, Coghlan M, Vigod S. Can we identify mothers at-risk for postpartum anxiety in the immediate postpartum period using the State-Trait Anxiety Inventory? J Affect Disord. 2013;150:1217–1220. doi: 10.1016/j.jad.2013.05.049.
    1. Hertzog MA. Considerations in determining sample size for pilot studies. Res Nurs Health. 2008;31(2):180–191. doi: 10.1002/nur.20247.
    1. Walton GD, Ross LE, Stewart DE, Grigoriadis S, Dennis CL, Vigod S. Arch Womens Ment Health. 2014. Decisional conflict among women considering antidepressant medication use in pregnancy.
    1. Dowswell T, Bedwell C, Lavender T, Neilson JP. Transcutaneous electrical nerve stimulation (TENS) for pain relief in labour. Cochrane Database Syst Rev. 2009;2:CD007214.

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