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A case series of repetitive transcranial magnetic stimulation in the treatment of major depression during pregnancy

Open AccessPublished:February 02, 2022DOI:https://doi.org/10.1016/j.brs.2022.01.021

      1. Introduction

      Women are more likely to experience depression during their childbearing years than during any other time in life [
      • Evans J.
      • Heron J.
      • Francomb H.
      • Oke S.
      • Golding J.
      Cohort study of depressed mood during pregnancy and after childbirth.
      ]. Depressive symptoms occur in approximately one in five pregnant women. There are many maternal and fetal risks associated with peripartum depression. Depressed, pregnant women are more likely to neglect prenatal care, abuse drugs and alcohol [
      • Tjoa C.
      • Pare E.
      • Kim D.R.
      Unipolar depression during pregnancy: nonpharmacologic treatment options.
      ] and have adverse neonatal outcomes, such as preterm birth [
      • Hanna E.Z.
      • Faden V.B.
      • Dufour M.C.
      The motivational correlates of drinking, smoking, and illicit drug use during pregnancy.
      ], lower birth weight [
      • Field T.
      • Diego M.
      • Hernandez-Reif M.
      • Figueiredo B.
      • Deeds O.
      • Ascencio A.
      • Schanberg S.
      • Kuhn C.
      Comorbid depression and anxiety effects on pregnancy and neonatal outcome.
      ] and a higher rate of neonatal care unit (NICU) admission [
      • Chung T.K.
      • Lau T.K.
      • Yip A.S.
      • Chiu H.F.
      • Lee D.T.
      Antepartum depressive symptomatology is associated with adverse obstetric and neonatal outcomes.
      ]. Postpartum depression may also negatively influence mother-infant bonding, child development, and child behavior [
      • Tjoa C.
      • Pare E.
      • Kim D.R.
      Unipolar depression during pregnancy: nonpharmacologic treatment options.
      ].
      It is essential to have safe and effective treatment options for peripartum depression. Psychotherapy is considered the primary recommended treatment [
      • Tjoa C.
      • Pare E.
      • Kim D.R.
      Unipolar depression during pregnancy: nonpharmacologic treatment options.
      ]. However, for patients with moderate to severe depressive symptoms, psychotherapy may not be sufficient, and medications may be indicated. Research reports 70–80% of pregnant women prefer not to take antidepressants [
      • Kim D.
      • Epperson C.
      • Pare E.
      • Gonzalez J.
      • Parry S.
      • Thase M.
      • Cristancho P.
      • Sammel M.
      • O'Reardon J.
      An open label pilot study of transcranial magnetic stimulation for pregnant women with major depressive disorder.
      ]. Large database and registry studies document that neonates of women who take antidepressants during pregnancy have an increased risk of seizure [
      • Udechuku A.
      • Nguyen T.
      • Hill R.
      • Szego K.
      Antidepressants in pregnancy: a systematic review.
      ], NICU admission [
      • Udechuku A.
      • Nguyen T.
      • Hill R.
      • Szego K.
      Antidepressants in pregnancy: a systematic review.
      ], respiratory distress and low Apgar scores [
      • Udechuku A.
      • Nguyen T.
      • Hill R.
      • Szego K.
      Antidepressants in pregnancy: a systematic review.
      ]. Research suggests selective serotonin reuptake inhibitors (SSRIs) can lead to higher risks of fetal cardiac septal defects, persistent pulmonary hypertension of the newborn, preterm birth, and neonatal withdrawal [
      • Tjoa C.
      • Pare E.
      • Kim D.R.
      Unipolar depression during pregnancy: nonpharmacologic treatment options.
      ].
      Electro-convulsive therapy (ECT) is also considered safe during pregnancy. However, ECT requires anesthetic agents and neuromuscular blockers, and poses a small risk of premature labor and placental abruption [
      • Magnezi R.
      • Aminov E.
      • Shmuel D.
      • Dreifuss M.
      • Dannon P.
      Comparison between neurostimulation techniques repetitive transcranial magnetic stimulation vs electroconvulsive therapy for the treatment of resistant depression: patient preference and cost-effectiveness.
      ].
      Past research on repetitive transcranial magnetic stimulation (rTMS) supports rTMS as a safe and effective treatment for pregnant women with major depressive disorder (MDD). Data suggests that, compared to ECT, rTMS has fewer side effects for both mother and fetus [
      • Magnezi R.
      • Aminov E.
      • Shmuel D.
      • Dreifuss M.
      • Dannon P.
      Comparison between neurostimulation techniques repetitive transcranial magnetic stimulation vs electroconvulsive therapy for the treatment of resistant depression: patient preference and cost-effectiveness.
      ]. Research to date using rTMS for the treatment of MDD during pregnancy has investigated lower motor threshold (MT) percentages, reduced pulses per session, and fewer total number of sessions compared to standard of care rTMS protocols. We conducted a case series of pregnant women with MDD treated with full intensity rTMS to evaluate efficacy and safety.

      2. Methods

      Five pregnant patients, aged 32–38, were treated with rTMS during their second or third trimester of pregnancy at a single clinical site, Neuro Wellness Spa Manhattan Beach, between 2017 and 2021. Prior to the initiation of rTMS, all five patients met criteria for major depressive disorder, recurrent (based on DSM-V diagnostic criteria) of moderate to severe severity (based on a 9-item Patient Health Questionnaire [PHQ-9] score ≥10 or a PHQ-9 score ≥20, respectively). PHQ-9 was assessed at baseline and around session 30.
      rTMS was delivered using the MagPro R30 equipped with a figure-of-eight coil (C–B60). The rTMS protocol consisted of 29–42 sessions. All patients received both theta burst stimulation (TBS) and single pulse (SP) stimulation at each session, an atypical rTMS protocol utilized at this treatment site. Four patients received 50Hz intermittent TBS to the left dorsolateral prefrontal cortex (DPFC) at 80% motor threshold (MT) for 200 pulses followed sequentially by 10Hz intermittent SP stimulation to the left DPFC at 120%MT for 3000 pulses and 50Hz continuous TBS to the right DPFC at 80%MT for 1200 pulses. One patient, with significant comorbid anxiety, received 50Hz intermittent TBS to the left dorsolateral prefrontal cortex (DPFC) at 80% motor threshold (MT) for 200 pulses followed sequentially by 1Hz intermittent single pulse stimulation to the right DPFC at 120%MT for 1500 pulses. MT location was determined according to a standardized surface anatomy approach. Stimulation site was based 5.5 cm forward from the MT location. The MT location and value were determined by visual observation of finger movement. MT was rechecked once or twice during treatment, around session 10 and session 20. Sessions were administered five days a week. The treatment protocol intensity was similar, in terms of %MT, total number of pulses per session and total number of sessions, to current recommendations for rTMS use in non-pregnant individuals with MDD. Neonatal records documenting gestational age, maternal/infant complications, and APGAR scores were reviewed.

      3. Results

      Headache in one patient, leading to rTMS discontinuation after 29 sessions, was the only adverse event.
      The mean PHQ-9 score at baseline was 17.80 (SD 4.02), and the mean PHQ-9 score at session 30 was 5.20 (SD 1.64). Change in depression severity was measured by comparing baseline and final PHQ-9 scores (Fig. 1). All women exhibited a ≥50% decrease in PHQ-9 scores, signifying a treatment response. Four women achieved a final PHQ-9 score of ≤5, indicating remission.
      Fig. 1
      Fig. 1Patient TMS information, including: Age during TMS; Medications taken during TMS; Number of TMS sessions; Baseline and Final PHQ-9 scores. Birth information, including: Gestational age at delivery; Baby sex; Birth weight and length; Mode of delivery; APGAR 1 and 5; Delivery complications; Major congenital malformations; NICU admission; Assessment by Pediatrician.
      There were no adverse pregnancy or fetal outcomes. All deliveries were spontaneous vaginal deliveries without complications. All infants were born >35 weeks gestational age. The infants’ mean 1-min and 5-min APGAR scores were 8.6 and 8.8, respectively. There were no NICU admissions or congenital malformations. All infants were discharged with their mother.

      4. Discussion

      To our knowledge, this is the first report of clinical outcomes for full intensity rTMS (standard of care MT percentages, total number of pulses per session and total number of sessions) in pregnant women with MDD. Given the small sample size, no conclusions can be made regarding efficacy or safety. The results, however, suggest that full intensity rTMS was a safe and effective treatment for these patients with MDD during their second and third trimester of pregnancy. 100% responded to treatment, and 80% achieved remission. These results support previous research of rTMS as an effective treatment for women experiencing peripartum depression [
      • Kim D.
      • Epperson C.
      • Pare E.
      • Gonzalez J.
      • Parry S.
      • Thase M.
      • Cristancho P.
      • Sammel M.
      • O'Reardon J.
      An open label pilot study of transcranial magnetic stimulation for pregnant women with major depressive disorder.
      ,
      • Kim D.R.
      • Wang E.
      • McGeehan B.
      • Snell J.
      • Ewing G.
      • Iannelli C.
      • O'Reardon J.P.
      • Sammel M.D.
      • Epperson C.N.
      Randomized controlled trial of transcranial magnetic stimulation in pregnant women with major depressive disorder.
      ]. Compared to past rTMS studies during pregnancy utilizing reduced intensity rTMS, this study demonstrates higher response and remission percentages [
      • Kim D.
      • Epperson C.
      • Pare E.
      • Gonzalez J.
      • Parry S.
      • Thase M.
      • Cristancho P.
      • Sammel M.
      • O'Reardon J.
      An open label pilot study of transcranial magnetic stimulation for pregnant women with major depressive disorder.
      ,
      • Kim D.R.
      • Wang E.
      • McGeehan B.
      • Snell J.
      • Ewing G.
      • Iannelli C.
      • O'Reardon J.P.
      • Sammel M.D.
      • Epperson C.N.
      Randomized controlled trial of transcranial magnetic stimulation in pregnant women with major depressive disorder.
      ].
      Limitations of this study are the small sample size and the atypical rTMS protocol. Strengths include the delivery of full intensity rTMS, the use of validated outcome measures, and the inclusion of neonatal outcomes. This study does provide further support that rTMS can be used safely during pregnancy and suggests that full intensity rTMS may ultimately develop into a promising treatment strategy for pregnant women with MDD.

      Declaration of competing interest

      The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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