By Paul Croarkin, DO, Research Committee Co-chair and Philip Janicak, MD, Research Committee Member

Introduction

Perinatal depressions are serious, debilitating conditions which are often under-recognized; and, even when properly diagnosed, often sub-optimally treated.  Notably, they can contribute to problematic maternal behaviors such as substance use, poor self-care, non-adherence to prenatal care, and a heightened risk for suicide. Maternal outcomes and the pathophysiology of untreated depression create challenges from conception throughout development via epigenetic mechanisms, aberrations in fetal brain development, and mother-child bonding. For example, offspring of depressed mothers are at an increased risk for future psychiatric disorders and related functional impairment.1,2

Standard treatment approaches of perinatal depression include evidence-based psychotherapies such as cognitive behavioral therapy (CBT) or interpersonal psychotherapy (IPT). Selective serotonin re uptake inhibitors (SSRIs) are the mainstay pharmacologic approach, often used in conjunction with psychotherapy. Studies consistently demonstrate that many mothers’ are hesitant about taking antidepressants while pregnant or nursing.2  As a result, both researchers and clinicians have considered the potential role for noninvasive brain stimulation modalities such as repetitive transcranial magnetic stimulation (TMS), as an alternative and possibly safer intervention for perinatal depressions. TMS is an appealing option given the lack of systemic effects that are typically associated with medications which can adversely impact the developing fetus or nursing infant.  Unfortunately, research and data collection in this area is understandably challenging.1

Literature Review

Dr. Debra Kim and colleagues recently summarized the existing literature involving TMS for treatment of perinatal depression.1  Notably, much of this literature involves case studies and open trials and therefore must be interpreted with caution.3-7  Further, a wide range of TMS dosing schedules, coil locations, and treatment courses have been undertaken at every stage of pregnancy and postpartum.  Mindful of these caveats, early results demonstrate promising outcomes in terms of maternal-fetal well-being.1

Pregnancy

In 2011, Kim and colleagues treated 10 depressed pregnant women during the 2nd or 3rd trimester employing 20 sessions of 1Hz TMS at 100% motor threshold over the right dorsolateral prefrontal cortex. With this approach, 7 women achieved response (i.e., at least a 50% reduction from baseline scores) as assessed with the 17-Item Hamilton Depression Rating Scale (HDRS-17). Four patients reported mild headaches but there were no other adverse events.8In 2014, Hizh Sayar and colleagues treated 30 pregnant woman during the 1st, 2nd or 3rd trimester employing 18 sessions of 25 Hz TMS at 100% motor threshold applied over the left dorsal lateral prefrontal cortex.  Notably, there was a significant decrease in the mean HDRS-17 score from baseline (p < 0.001) after the treatment course. There were no reported adverse maternal or fetal events.9

Neonatal Outcomes

In a 2015 case control study, Erylimaz and colleagues compared the children of mothers who received treatment with TMS during pregnancy (n=30) to a control group of children whose mothers went untreated for their prenatal depression (n=26).  In the TMS group, 2 infants had jaundice and 1 had febrile seizures.  In the control group, 3 infants had jaundice and 1 had a low birth weight. Further, there were no significant cognitive or motor delays in the offspring of mothers treated with TMS.10

Postpartum Depression

In 2010, Garcia and colleagues treated 9 women with postpartum depression employing 20 sessions of 10 Hz TMS at 120% motor threshold applied over the left dorsal lateral prefrontal cortex.  By week 2, patients experienced significant improvement in depressive symptoms from baseline (p<0.008) as assessed with the 24-Item HDRS scale. Furthermore, 8 patients achieved remission (ie., HDRS-24 < 10 and Clinical Global Impressions Severity Scale =1) at week 4 and 7 patients still met remission criteria at 6 months.11 In 2012, Myczkowski and colleagues treated 14 women with postpartum depression employing 20 sessions of 5 Hz TMS at 120% motor threshold or a sham procedure applied over the left dorsal lateral prefrontal cortex. Active TMS yielded improvement at week 6 as assessed with the HDRS-17. Two patient’s reported mild scalp pain but there were no other adverse events.12

Conclusion 

Collectively, this body of work is encouraging and raises a number of important issues that should be considered. Thus, initial evaluation for possible TMS treatment in this population requires close collaboration with the family, obstetrician, primary psychiatrist, and a TMS expert.  The risks of untreated depression and the knowledge gaps regarding TMS, especially in this population, should be carefully reviewed with the family to facilitate an informed decision.  While a variety of TMS strategies have been utilized, it appears that right-sided, low frequency TMS might be the optimal approach to maximize safety, tolerability and clinical efficacy. Further, relatively shorter treatment courses (e.g., 15-20 sessions) appear to have beneficial effects for perinatal depression. Notably, TMS treatment of mothers beyond 24 weeks of pregnancy should employ a 30 degree lift tilt position to avoid supine hypertension. This can be accomplished by positioning the patient on her left side and placing a wedge cushion under the right lower back to prevent the inferior vena cava compression syndrome.1,13

Given the limited data and systematic reports on clinical experience for perinatal depression, the Clinical TMS Society Research Committee is interested in collecting and synthesizing any available data and clinical impressions. Please contact Paul Croarkin (croarkin.paul@mayo.edu) or Philip Janicak (pjanicak@gmail.com) if you are interested in contributing to this effort.

  1. Kim DR, Snell JL, Ewing GC, O’Reardon J. Neuromodulation and antenatal depression: a review. Neuropsychiatric disease and treatment. 2015;11:975-982.
  2. Stewart DE, Vigod S. Postpartum Depression. The New England journal of medicine. 2016;375(22):2177-2186.
  3. Burton C, Gill S, Clarke P, Galletly C. Maintaining remission of depression with repetitive transcranial magnetic stimulation during pregnancy: a case report. Archives of women’s mental health. 2014;17(3):247-250.
  4. Klirova M, Novak T, Kopecek M, Mohr P, Strunzova V. Repetitive transcranial magnetic stimulation (rTMS) in major depressive episode during pregnancy. Neuro endocrinology letters. 2008;29(1):69-70.
  5. Nahas Z, Bohning DE, Molloy MA, Oustz JA, Risch SC, George MS. Safety and feasibility of repetitive transcranial magnetic stimulation in the treatment of anxious depression in pregnancy: a case report. The Journal of clinical psychiatry. 1999;60(1):50-52.
  6. Zhang D, Hu Z. RTMS may be a good choice for pregnant women with depression. Archives of women’s mental health.2009;12(3):189-190.
  7. Zhang X, Liu K, Sun J, Zheng Z. Safety and feasibility of repetitive transcranial magnetic stimulation (rTMS) as a treatment for major depression during pregnancy. Archives of women’s mental health. 2010;13(4):369-370.
  8. Kim DR, Epperson N, Pare E, et al. An open label pilot study of transcranial magnetic stimulation for pregnant women with major depressive disorder. Journal of women’s health (2002). 2011;20(2):255-261.
  9. Hizli Sayar G, Ozten E, Tufan E, et al. Transcranial magnetic stimulation during pregnancy. Archives of women’s mental health. 2014;17(4):311-315.
  10. Eryilmaz G, Sayar GH, Ozten E, et al. Follow-up study of children whose mothers were treated with transcranial magnetic stimulation during pregnancy: preliminary results. Neuromodulation : journal of the International Neuromodulation Society. 2015;18(4):255-260.
  11. Garcia KS, Flynn P, Pierce KJ, Caudle M. Repetitive transcranial magnetic stimulation treats postpartum depression.Brain stimulation. 2010;3(1):36-41.
  12. Myczkowski ML, Dias AM, Luvisotto T, et al. Effects of repetitive transcranial magnetic stimulation on clinical, social, and cognitive performance in postpartum depression. Neuropsychiatric disease and treatment. 2012;8:491-500.
  13. Kim DR, Wang E. Prevention of supine hypotensive syndrome in pregnant women treated with transcranial magnetic stimulation. Psychiatry research. 2014;218(1-2):247-248.

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