Acceptability, Safety and Efficacy of Transcranial Magnetic stimulation (TMS) during Pregnancy
Rachel Ogbuoji M.B.B.S MPH, Andrea Hernandez-Gonzalez MD.

Introduction
Depression is a common mental illness during pregnancy with reported prevalence of depression in this group ranging from 7.4% in the first trimester to 12.0% in the third trimester1 If left untreated, maternal depression may pose a potential risk factor for negative maternal health and birth outcomes. Unfortunately, this unique population faces a challenge with using pharmacotherapy to treat depression due to the unclear adverse effects on the unborn fetus2 3 4.  Also, some women may experience drug-resistant depression. In addition, pregnant women choose pharmacotherapy as the least option for treating depression5 6. Given this context, non-pharmacological treatment seems to be a more acceptable alternative. 
TMS is a non-pharmacological treatment approved by the FDA for treatment-resistant depression7. This may be an option to treat depression during pregnancy as it is non-invasive, does not require the use of sedating medications that may cross the placenta and does not cause cognitive impairment in patients8. However, the safety and efficacy of TMS use during pregnancy is not clear as very little research evidence is available. Therefore, this literature review aims to find out what is known about the acceptability, safety and efficacy of using TMS to treat pregnant women with depression and also assess the effect of this procedure on the fetus.

Method
We searched the following search engines; MEDLINE, GOOGLE SCHOLAR, Psych INFO, and SCOPUS between 1995 and 2018 using the following search terms: “transcranial magnetic stimulation” and “pregnancy” and “depression”. 152 articles were initially generated, but only fourteen met the criteria to be selected. 

Review of literature

     Acceptability during pregnancy: Pregnant women usually prefer non-pharmacological treatment for depression. However, TMS is not the first non-pharmacological option that is chosen in people without knowledge about the procedure. A study conducted in 2011 to access the acceptability of repeated TMS (rTMS) for treatment of depression during pregnancy (Kim et al 2011) found that TMS was considered an unacceptable option. However, after the women were shown an informational video, 15.7% of the women considered TMS as an acceptable treatment option. 

     Safety to pregnant mother: The first case report conducted to access the safety of TMS in pregnancy was in 1999 (Nahas et al). TMS was found to be safe for a 36-year-old woman in her second trimester with no reported side effects. Several other studies (Zhang et al 2010, Burton et al 2014,) have all reported TMS to be safe for the mother with no observed major side effects. Even exposure to high frequency TMS to 100% of the motor threshold was well tolerated by the mothers (Hizli et al 2014). However, transient headache and scalp pain were reported as some minor side effects (Kim et al 2011, Janicak et at 2008). Supine hypotension  syndrome was also reported in one study and interestingly both women were in their third trimester ( Kim and Wang 2014).

     Efficacy in treating depression: Repetitive TMS have been successfully used to relieve symptoms of major depression in pregnant women including treatment-resistant depression during the first, second and third trimester (Nahas et al 1999, Zhang and Hu 2009, Ferrao and Felipe de Silva 2018). One study showed a 70% response rate to rTMS treatment with a decrease in the Hamilton depression score by 50% or more (Kim et al 2011). Another study with 30 depressed pregnant women who had rTMS resulted in improvement of symptoms in 41.4% of patients, remission in 20.7% while 3.4% had a worsening of their Hamilton depression score. (Hizli et all 2014). TMS have also been successfully used to treat bipolar II in a 32-year-old woman at 20 weeks gestation who was intolerant to antidepressants. (Xiong et al 2018). Low frequency TMS was also reported to ameliorate akathisia in pregnancy (Guerero and Molina 2017)

     Effect on fetus: Repetitive TMS has not been shown to be associated with adverse fetal outcome during pregnancy or in the post-natal period (Kim  D R et al 2011, Burton et al 2014, Hizli et al 2014). There is currently no evidence that suggests poorer cognitive or motor development in children 16-36 months whose mothers had rTMS exposure during pregnancy compared to children who were not exposed to TMS during pregnancy (Eryilmaz et al 2015). It is recommended that the safe limit of fetal exposure to electric and magnetic field from TMS should have a maximum peak electric field of 100mV/m or less within the fetal volume (Yanamadala et al 2018). This value is far less than what is generally recommended.  

Conclusion
TMS acceptability increase with knowledge about the procedure. The use of TMS in pregnancy is an effective non-pharmacological treatment for major depression. It is generally safe and well tolerated with headache and dizziness reported as minor side effects. No adverse outcome has been reported in the fetus or in the cognitive or motor development of children between 16-36 months old. 
 
Recommendations
1)More information and awareness needs to be provided about the procedure so that patients can make an informed decision.
2) More follow-up studies are needed to assess the effect of TMS on the neuro-development of children that were exposed to TMS in-utero.
3) Studies should explicitly indicate which type of TMS that was performed since studies have shown that HF-TMS has better efficacy compared to sham-rTMS.
4) Studies on duration of TMS treatment, timing (trimester), frequency and positioning that is the safest for pregnant women and their fetus should be established for both the aute and maintenance phase of treatment.
5) Studies should include and report changes in vital signs of the mother and fetus during TMS procedure.

References
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01 - ACCEPTABILITY, SAFETY AND EFFICACY OF TRANSCRANIAL MAGNETIC STIMULATION (TMS) DURING PREGNANCY