Repetitive Transcranial Magnetic Stimulation Treatment for Peripartum Depression: Systematic Review & Meta-Analysis

Repetitive Transcranial Magnetic Stimulation Treatment for Peripartum Depression: Systematic Review & Meta-Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Repetitive Transcranial Magnetic Stimulation Treatment for Peripartum Depression: Systematic Review & Meta-Analysis Hyunejune Lee, Sungmin Kim, Ji Yean Kwon This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-108764/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Feb, 2021 Read the published version in BMC Pregnancy and Childbirth → Version 1 posted 10 You are reading this latest preprint version Abstract Background Peripartum depression is a common disorder with very high potential hazards for both the patients and their babies. The typical treatment options include antidepressants and electroconvulsive therapy. However, these treatments do not ensure the safety of the fetus. Recently, repetitive transcranial magnetic stimulation has emerged as a promising treatment for neuropathies as well as depression. Nevertheless, many studies excluded pregnant women. This systematic review was conducted to confirm whether repetitive transcranial magnetic stimulation was a suitable treatment option for peripartum depression. Methods We performed a systematic review followed the PRISMA guidelines. We searched studies in the MEDLINE, PsycINFO, EMBASE, and Cochrane library databases published until the end of September 2020. Eleven studies were selected for the systematic review, and five studies were selected for quantitative synthesis. Data analysis was conducted using Comprehensive Meta-Analysis 3 software. The effect size was analyzed using the standardized mean difference and the 95% confidence interval (CI) was determined by the generic inverse variance estimation method. Results The therapeutic effect size of repetitive transcranial magnetic stimulation for peripartum depression was 1.394 (95% CI: 0.920 – 1.843), and the sensitivity analysis effect size was 1.074 (95% CI: 0.777 – 1.233), indicating a significant effect. The side effect size of repetitive transcranial magnetic stimulation for peripartum depression was 0.346, (95% CI: 0.214 – 0.506), which was a meaningful result. There were no serious side effects to the mothers or fetuses. Conclusions From a variety of perspectives, repetitive transcranial magnetic stimulation can be considered an alternative treatment to treat peripartum depression to avoid the exposure of fetuses to drugs and the severe side effects of electroconvulsive therapy. Further research is required to increase confidence in the results. Maternal & Fetal Medicine repetitive transcranial magnetic stimulation rTMS peripartum depression pregnancy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Background Peripartum depression (PPD) is defined as major depression occurring within the gestational period and four weeks after childbirth. [1]. PPD is a common disease that 10 – 20% of pregnant women experience [2], and PPD patients incur a massive lifetime expense of 75,728 pounds (USD $95,656) [3]. PPD threatens not only the mother’s health by causes hormonal imbalance [4], alcohol and substance abuse [5], and increases maternal suicide [6]. The health of the fetus is also affected by premature birth [7] and low birth weight [8]. PPD also interferes with creating a stable attachment in the growth process of infants, which can result in self-control and cognitive function behavioral issues [9]. The methods for treating PPD are mainly electroconvulsive therapy (ECT) and antidepressants [10]. Although both of them have proven treatment effectiveness for PPD [11-14], some concerns for the safety of pregnant women and fetuses have been raised. Antidepressants relieve depression by regulating the neurotransmitters that make people feel happy [15]. Neurotransmitters released from pre-synaptic neurons are reabsorbed or decomposed by monoamine oxidase enzymes in the process of transferring them to the neurons from the synapses. Antidepressants reduce neurotransmitter decomposition by interfering with their reabsorption and the activity of monoamine oxidase enzymes, thereby alleviating depression [16]. Antidepressants are one of the most used treatment methods for PPD, but there are some concerns. Because components of antidepressants can pass through the placenta [17], these could have a chemical effect on the fetus. Pregnant women taking antidepressants have a 7-fold increased risk of spontaneously induced abortion [18, 19], a more than 3-fold increased risk of fetal infections [20], and increased risks of premature birth and underweight babies [21], autism spectrum disorder in the baby [22], increased risk of motor, speech, and scholastic disorder [23], cardiac defects [24] and persistent pulmonary hypertension [25]. Also, infants can be exposed to antidepressants and their metabolites during breastfeeding [26], which could increase monoamine oxidase levels and affect the functional maturity of the infant’s brain [27]. Side effects such as decreased feeding [28], colic, and irritability [29] have been reported. Another treatment, ECT, is a method of delivering a stimulating electrical shock to the brain to relieve depression. Electric shocks affecting neurons and chemicals in the brain produce short and controlled seizures, which have excellent effects on various neurological disorders [30]. However, treating pregnant women with ECTs can cause adverse effects such as vaginal bleeding and miscarriage [31], uterine contractions [32], abdominal pain [33], and preeclampsia [34]. Clinicians recommend these treatments because the risk of the treatment is smaller than the risk of PPD [35, 36] and their effectiveness has been proven. However, considering the safety concerns of these treatments for the fetus and mother, research to identify safer treatment methods is needed. With the recent development in brain stimulation research, many researchers are increasingly trying to use brain stimulation for various neurological treatments [37]. One type of brain stimulation, repetitive transcranial magnetic stimulation (rTMS) stimulates the brain’s dorsolateral prefrontal cortex (DLPFC) with magnetic fields to induce the degeneration of neurons and activate the neural system of the brain to relieve depression [38]. Using rTMS to treat PPD is still reluctant [39-41], although studies have shown that rTMS is safe [42] and effective for treating several neurological diseases [43-45]. Thus, in this paper, we conducted a systematic review and meta-analysis to confirm whether rTMS treatment was suitable for PPD. There are few systematic review studies on rTMS treatment for PPD [46-49], but no studies statistically analyzed the therapeutic effects and safety and considered the adverse effects on fetuses. To investigate these problems, we conducted a meta-analysis to confirm the effect size of the therapeutic effects and safety and extended the range of patients from pregnant patients to one year after childbirth to identify the effect on the fetuses. Methods The systematic review followed the PRISMA guidelines (registration number CRD42020197855). Key questions The criteria used in selecting the relevant studies included patients from the pregnancy period to one year after childbirth, intervention with TMS; no limits on the comparators, and outcomes measured by the degree of depression alleviation. The detailed key questions were: (1) Is rTMS effective for PPD? What is the effect size of rTMS for PPD? (2) Does rTMS have maternal and fetal side effects? What is the effect size of the side effects caused by rTMS? Inclusion and exclusion criteria In general, the studies used for the meta-analysis were randomized controlled trials (RCTs), but, non-randomized studies (NRS) were also included in the meta-analysis, and case studies were included in the systematic review because only a small number of randomized trials provided evidence of the effects of the interventions [50] associated with pregnancy. Before inclusion, the non-randomized studies were evaluated to verify that the patients, interventions, comparisons, and outcomes were set appropriately by the Cochrane algorithm. If systematic reviews or meta-analyses were included, we checked the included studies and references. The criteria for exclusion were (1) experimental studies with animals, (2) studies not published in English, (3) studies that were not original (if there was only abstract, the original text was requested in an e-mail to the author), (4) symptoms of baby blues or postpartum psychosis, and (5) major depressive disorder that did not occur from pregnancy to one year after childbirth. Literature search strategy We performed a literature search of studies published before the end of September 2020 using EMBASE, MEDLINE, PsycINFO, and the Cochrane Library. In the literature search, the medical indications and treatment methods were searched using Boolean models. The indications search terms were peripartum depression or antepartum depression or postpartum depression or pregnancy or perinatal, and the treatment searches used rTMS or repeated transcranial magnetic stimulation or TMS or transcranial magnetic stimulation. The detailed search strategies are presented in Appendix 1. To minimize the omission of data and increase the reliability, two researchers independently reviewed the literature and, if the opinions of the researchers differed, the studies were reviewed together and an agreement was reached. Data extraction The data extraction items for the studies that were finally selected through the literature screening included the characteristics of the study design, demographic characteristics, the characteristics of the treatment effect variables known to affect treatment effectiveness [51], and the characteristics of the effects on the mother and fetus. The details are presented in Figure 1. Risk of bias assessment After the literature screening, a bias evaluation of the studies was performed by two evaluators independently to clarify ambiguous differences between the reporting quality and research quality. Different evaluation methods were applied according to the study design. RCT studies were examined using the risk-of-bias 2 (ROB2) tool [52] and the NRS were examined using the Risk of Bias Assessment Tool for Non-randomized Studies (ROBINS-I) [53]. Case reports and series were evaluated used the methodological quality tool [54] because they could be adopted as evidence of new treatments [55]. The final judgment on the overall risk of bias was agreed upon between the two evaluators and publication bias was visually reviewed through funnel plots, and additionally, statistically confirmed through Egger's regression. Data analysis Data analysis was conducted using Comprehensive Meta-Analysis 3 software (CMA3). The effect size was used standardized mean difference (SMD) was obtained using two-group, pre-post data in the RCTs, and one group pre-post data for the NRS [56]. For the 95% CI and the correlation coefficient value of 0.5, the generic inverse variance estimation method was used [57]. Safety was assessed using the effect size of the side effects and the effect size was calculated by the same method as the treatment effect. The calculations are presented as a Forest plot. Heterogeneity was determined using the statistical test method Cochrane's Q test and the I-squared (I²) statistic. If the p -value of the Q test value exceeded 0.1 and the I² statistic exceeded 50%, a random-effects model was applied, and if the Q test value was less than 0.1 and the I² statistic was less than 50%, a fixed-effects model was applied. Results Search results We conducted a literature search following the PRISMA FLOW guidelines. Of the 229 studies identified in the database, 128 remained after the removal of the duplicates. Ninety-eight studies were excluded because they did not meet the inclusion and exclusion criteria. We performed a full-text review of 30 studies to confirm whether they were suitable for our research purposes. Finally, 11 studies suitable for the systematic review and five studies suitable for meta-analysis were selected to confirm the therapeutic effect and safety of rTMS. There were three studies with only abstracts, so we requested the original text by email, but no author responded. Characteristics of the selected studies Eleven studies identified the efficacy and safety of rTMS for PPD, two RCT studies [58, 59], four NRS [60-63], and five case studies [63-67]. One NRS study was excluded from the meta-analysis since the study did not report detailed outcomes. The total number of participants was 101, 84 of whom received active rTMS treatment. During pregnancy, 65 patients were treated with rTMS, and most of them were in the second and third trimesters of pregnancy. Seventeen patients were treated for postpartum depression, and two patients were treated during pregnancy and after delivery. Although 20 participants were treated with antidepressants [60, 62, 65, 68] along with rTMS, their antidepressant doses were stable for two to four weeks, and one participant was treated with clonazepam for insomnia [61]. The treatment parameters and protocols in each study were all different, which seemed to be because the protocol for TMS therapy for perinatal depression has not yet been accurately established. Twenty-two patients were stimulated to the right DLPFC [58, 60, 65, 66], 79 to the left DLPFC [59, 61-65, 69], and the patients in two studies [65, 68] were stimulated on both sites. The patients who were stimulated on the right DLPFC showed symptoms of anxiety and were treated with a frequency of less than 1 Hz, which is relatively less than that used to stimulate the left DLPFC (more than 5 Hz). The researchers considered the interval time and duration of stimulation to minimize side effects such as seizures and did not show any common characteristics for the other treatment parameters. Table 1 Characteristics of the subjects in the included studies Study Study design Subjects Age Gestational age Psychiatric diagnosis Simultaneous treatment D. R. Kim et al., 2019 [58] Randomized controlled trial Active 11 30.13 ± 5.78 22.19 ± 7.11 (Weeks) MDD Free Sham 11 26.41 ± 5.11 25.62 ± 7.61 (Weeks) Myczkowski et al., 2012 [59] Double-blind randomized controlled trial Active 8 29.63 ± 6.37 4.13 ± 2.85 (Month) MDD Free Sham 6 26.67 ± 7.15 3.50 ± 2.74 (Month) D. R. Kim et al., 2011 [60] Non-randomized controlled trial 10 31.2 ± 5.6 25.8 ± 5.16 (weeks) MDD 4 patients treated with antidepressants Hizli Sayar et al., 2014 [62] Non-randomized controlled trial 30 32.69 ± 3.69 14.26 ± 8.25 (weeks) MDD 12 patients treated with antidepressants Garcia et al., 2010 [61] Non-randomized controlled trial 7 34.11 ± 6.05 After birth 30 days to 1 year MDD Free Tarhan et al., 2012 [69] Non-randomized controlled trial 7 * * MDD * Zhang et al., 2010 [64] Case report 1 28 14 (weeks) MDD Free Tan et al., 2008 [63] Case report 1 30 From 0 to postpartum period MDD Free Ferra˜o et al., 2018 [65] Case report 3 (Left) 35.7 ± 2.05 6.67 ± 3.06 MDD 2 patients treated with antidepressants 1 (Right) 36 8 1 patient treated with antidepressants Cohen et al., 2008 [66] Case report 1 30 Until 20 (weeks) MDD Free Monika Klírová et al [67] Case report 1 (Left) 30 16 MDD Treated with antidepressant 1 (Right) 30 31 MDD Treated with antidepressant *MDD: major depressive disorder Table 2 Characteristics of the treatments in the included studies Study Motor threshold Site of stimulation Frequency Number of pulses Inter-event interval Number of Sessions D. R. Kim et al., 2019 [58] 100% Right DLPFC* 1-Hz 900 60 s** on 60 s off 20 Myczkowski et al., 2012 [59] 120% Left DLPFC 5-Hz 1250 10 s on 20 s off 25 D. R. Kim et al., 2011 [60] 100% Right DLPFC 1-Hz 300 60 s on 60 s off 20 Hizli Sayar et al., 2014 [62] 100% Left DLPFC 25-Hz 1000 2 s on 30 s off 18 Garcia et al., 2010 [61] 120% Left DLPFC 10-Hz 150 4 s on 26 s off 20 Tarhan et al., 2012 [69] 100% Left DLPFC 25-Hz 1000 2 s on 30 s off 18 Zhang et al., 2010 [64] 90% Left DLPFC 1-Hz 1200 20 s off 42 Tan et al., 2008 [63] 110% Left DLPFC 25-Hz 1000 2 s on 28 s off 77 Ferra˜o et al., 2018 [65] 120% Left DLPFC 10-Hz 3000 * 42.67 Right DLPRC 1-Hz 1800 20 Cohen et al., 2008 [66] 110% Right DLPFC 1-Hz 1600 * 1 Monika Klírová et al [67] 100% Left DLPFC 20-Hz 2000 2 s on 30 s off 15 Right DLPRC 1-Hz 300 60 s on 60 s off 15 * DLPFC: dorsolateral prefrontal cortex; s, seconds Table 3 Characteristics of the outcomes in the included studies Study Instrument Pre-TMS**** Post-TMS Remission Response Side effects (mother) Infants D. R. Kim et al., 2019 [58] HDRS-17* 23.18 ± 3.54 9.27 ± 6.05 3 9 1 patient had a headache 3 preterm births 1 shoulder dystocia 22.27 ± 2.65 13.18 ± 8.00 2 5 Myczkowski et al., 2012 [59] HDRS-17 29.13 ± 5.64 18.50 ± 9.83 * * 2 patients had a mild headache * 26.67 ± 5.68 24.83 ± 7.60 D. R. Kim et al., 2011 [60] HDRS-17 24.4 ± 5.6 9.7 ± 6.1 3 7 4 patients had a mild headache. 1 patient had an episode of supine hypotension All infants were in the well-baby nursery Hizli Sayar et al., 2014 [62] HDRS-17 26.67 ± 5.58 13.03 ± 6.93 6 12 None None showed any abnormalities. Garcia et al., 2010 [61] HDRS-24 22.67 ±6.44 2.14 ± 3.19 8 9 Headache, site pain * Tarhan et al., 2012 [69] HDRS-17 * * 2 5 None All had healthy babies Zhang et al., 2010 [64] HDRS-24 35 8 1 1 None Healthy boy Tan et al., 2008 [63] HDRS-17 38 4 1 1 None No diagnosis of disease Ferra˜o et al., 2018 [65] HDRS-21 24.33 ± 5.24 7.33 ± 4.03 2 3 2 patients had discomfort at the application site. Preterm twins 12 6 1 1 Discomfort at the application site and sore throat Cohen et al., 2008 [66] HDRS-17 18 6 1 1 * The infant had normal neurologic development Monika Klírová et al., 2008 [67] MADRS** 33 2 * * None Healthy baby BDI*** 29 12 * * * HDRS: Hamilton Depression Rating Scale (HDRS-21,24 is an expanded version of the HDRS-17) ** MARDS: Montgomery-Åsberg Depression Rating Scale *** BDI: Beck Depression Inventory **** TMS: transcranial magnetic stimulation Therapeutic effects In the 11 studies selected for the systematic literature review, except for the study by Tarhan [69], which did not report the detailed treatment effects of rTMS, 76 patients had an average 59% improvement in depression. Thirty-seven percent of the participants showed depression remission (depression scale rating was lowered to that of a normal person), and 66% of the participants showed a response to rTMS (depression scale score reduced more than 50% compared to before treatment). In Kim's study [67], one of the RCT studies, 45.45% of the control group responded, whereas 81% of the experimental group responded, and the remission rate also showed a significant difference of 9% or more between the experimental group and the control group. Another RCT study also showed a difference in the depression scale of about 23% between the control group and the experimental group, showing a similar treatment effect to that of antidepressants [59]. In the NRS, the response rate of 56 participants was 33%, and the remission rate was 59%. In the study by Garcia et al. [61], the depression scale scores showed that all participants achieved remission, and all except one participant responded to rTMS. The other NRS also showed treatment effects, and in the case study, all nine participants responded to rTMS. All studies showed treatment effectiveness, but treatment effectiveness declined as the study design was refined. Evaluation of the heterogeneity of the studies for treatment effects showed a p- value of < 0.001 and an I 2 statistic of 71.933. Because the I 2 statistic exceeded 50%, a random-effects model was applied. The effect size of rTMS for PPD had an SMD of 1.394 (95% CI: 0.920 – 1.843), indicating a significant treatment effect (Z = 6.079, p < 0.01). Figure 3 shows the sensitivity analysis performed because we thought that the treatment effect in one study [61] was measured too high. Excluding this, the heterogeneity showed a p- value of < 0.01 and an I 2 statistic of 62.593, and because the I 2 value exceeded 50%, a random-effects model was applied. The effect size of rTMS for PPD had an SMD of 1.074 (95% CI: 0.777 – 1.233), indicating a meaningful treatment effect ( Z = 5.468 , p < 0.01 ) . The sensitivity analysis showed that the heterogeneity decreased, but the I 2 value still exceeded 50%, and the treatment effect was also slightly reduced, but the treatment effect was still significant. Safety In the 11 studies selected for systematic review, about 15% of the patients experienced side effects in the group receiving rTMS therapy. However, in the RCTs, there was no difference between the experimental groups and the control groups [58, 59], and there were minor side effects that did not worsen the patients’ health, such as headache [58, 60, 61, 65, 66] and pain at the stimulation site [61, 66]. Supine hypotension syndrome was reported as an adverse event in some mothers [60]. However, this is a disorder caused by posture during treatment and can be prevented after posture correction [70]. The side effects in the infants included preterm birth, and five fetuses experienced preterm birth, but all of the fetuses were healthy. Brachial plexus injury was reported as an adverse event in one fetus, but it was caused by the large shoulder of the fetus and was not a side effect of the treatment process [58]. Evaluation of the heterogeneity of the studies for the side effects showed a p -value of < 0.01 and an I 2 value of 46.631 and, because the I 2 value was less than 50%, a fixed-effects model was applied. The effect size of side effects had an SMD of 0.346, (95% CI : 0.214 – 0.506), indicating that rTMS had an effect on the occurrence of side effects (Z = -1.889, p = 0.059). Risk of bias According to the experimental design, the RCTs were evaluated by ROB2, the NRS by ROBIN-I, and the case studies were evaluated using a methodological quality tool. We evaluated the bias according to the guidance of the tool and assessed the overall bias as a low risk of bias if all domains of bias were low risk, a high risk of bias if there were one or more high-risk domains or many suspected risks. In the case of Myczkowski’s study [59], the study could have selective reporting bias because the planned outcomes were selectively reported. Bias in the outcomes measurements in the NRS was evaluated as moderate [60-63] because the study design of all of the NRS was open-label, meaning that the patients knew their treatment, and the risk of bias in Garcia’s study [61] was evaluated as high because there were missing data, which could have a significant impact on the outcome. The overall evaluation of bias was moderate, but this must be considered as it can cause over or underestimation of the effect sizes. The detailed risk of bias assessment for the domains is presented in Appendix 3. Figure 7 is a funnel plot showing the relationship between the sample size and the effect size to confirm publication bias. We visually checked whether the funnel plot was symmetrical and checked Egger's regression to determine statistically significant. Publication bias existed because the funnel plot was not symmetric and had a p -value of 0.01. However, without Garcia's study [61], which had a high risk of bias, the funnel plot had a symmetrical structure and a p -value of 0.121, so it can be said that there was no publication bias. In the case of safety, since there were fewer than 10 documents included, the minimum conditions for publication bias were not satisfied, and the publication bias of the side effects was not analyzed. Discussion The effect size of the therapeutic effect had an SMD of 1.394 (95% CI: 0.920 – 1.843), which was significant for treating depression [71] and except for Garcia’s study [61], in which reporting bias was suspected because of the selection reporting, the effect size SMD was 1.074, (95% CI: 0.777 –1.233), which was also a meaningful result. The studies excluded by the exclusion criteria also showed positive treatment effects of rTMS for PPD, supporting the treatment effect. In Brock's study, 14 out of 19 patients with rTMS achieved remission [72], and in Ozmut's study, eight out of 15 patients responded to rTMS [73]. Other studies also succeeded in improving the depression of patients with PPD using rTMS [74, 75]. It could be possible that the effect size was overestimated because the parameters that can affect the treatment effect, such as the site of stimulation, frequency, and interval time, were not established, and there was a risk of bias. However, even considering these points, the treatment potential was confirmed, and if a protocol becomes established, it is expected that more sophisticated effect sizes can be calculated. The effect size of TMS side effects had an SMD of 0.346 (95% CI: 0.214 – 0.506), which was significant [71]. However, the side effects of rTMS treatment on the mothers, such as headaches, discomfort, and pain in the stimulation area were minor, and these side effects disappeared at the end of the treatment process.. Some mothers experienced supine hypotension [60], but this was caused by a posture problem during treatment and could be prevented through postural correction [70]. All children born to mothers with rTMS treatment were born healthy. In one of the RCT studies that evaluated the child’s health condition by appearance-pulse-grimace-activity-respiration scores, the difference between the two groups was not significant [experimental group 8.36 (1.50), control group 8.73 (0.90), p = 0.501] [58]. There were five preterm births and one brachial plexus injury among the fetuses. Although 5% (5) of the study participants experienced preterm birth, two of these had already been warned of the risk of preterm birth by a biomedical test. Considering that the average proportion of women who undergo preterm birth worldwide is 9.1 to 13.4% [76], it is unlikely that a causal relationship exists between rTMS and preterm birth. However, further research on this is needed. Brachial plexus injury was reported as a side effect in one newborn, but it was not related to rTMS treatment [58], and there were no other side effects in the infants. One study that checked the child of a mother treated with rTMS reported that the exposure during pregnancy did not affect the cognitive or motor development of the child [77]. High frequencies above 40 Hz affect the lungs and immune system of the fetus [78, 79], and the maximum electromagnetic field applicable to the fetus is 800 mv/m [80]. However, the frequency used in rTMS treatment is generally 1 – 25 Hz, and the scale of the electromagnetic field is 100 mv/m [81]. Nevertheless, additional research should be conducted because there are many aspects not yet researched. Mothers do not prefer the current treatment for peripartum depression. They are not willing to take antidepressants because they are concerned not only about the side effects that they will suffer but also the side effects to the fetus [82, 83] Besides, 2.5% of mothers suffer from treatment-resistant depression and have to choose a different treatment method [84]. In one survey on depression treatments, only 1.2% of the population accepted ECT treatment [85]. Although the acceptance rate of rTMS was also low, when knowledge about the treatment was shared, the acceptance rate increased by more than 50%, showing the possibility as a treatment method for PPD [86]. From the side of economic efficiency, rTMS may be a good alternative for treating PPD. For example, rTMS might save $112 per quality-adjusted life years (QALY) compared to antidepressants [87] and might save $8515 per year compared to ECTs [88]. This could reduce anxiety about the cost, which was one of the risk factors that had the greatest impact on pregnant women [89], and consequently, the socioeconomic costs of peripartum depression might be reduced. Limitation and future study direction Regarding the limitations of the meta-analysis, our results showed high heterogeneity, and the reason may be heterogeneity due to methodological diversity because the parameters of rTMS varied from study to study, or heterogeneity due to coincidence because the analysis was conducted with small sample-sized studies. However, because the parameters vary according to the patient's situation (e.g., the stimulation site changes according to symptoms and the frequency changes according to the stimulation site), it should be judged as clinical heterogeneity. Our results might also be constrained by the lack of patients and studies. Thus, the effects of rTMS on PPD and should be interpreted with caution. Future research should focus on the effects in the prenatal and infancy periods and establish parameters for rTMS, such as the site stimulation or frequency. Conclusions We collected data from existing documents and identified 11 studies that were suitable for a systematic review, of which five are suitable for meta-analysis. According to the analysis of the included studies, the therapeutic effect size of rTMS for PPD showed an SMD of 1.394 (95% CI: 0.920 – 1.843), and the sensitivity analysis showed an SMD = 1.074 (95% CI: 0.777 – 1.233), which is a significant effect, but this effect size could be overestimated because more than 50% of the studies were NRS, and some studies were at risk of bias Nonetheless, rTMS seems to have potential as a treatment for peripartum depression. The side effects of rTMS for PPD had an SMD of 0.346, (95% CI: 0.214 – 0.506), which is meaningful. However, there were no serious side effects to the mothers or fetuses. From a variety of perspectives, the treatment of PPD using rTMS could be considered an alternative treatment to avoid exposure of the fetus to drugs and the severe side effects of ECT. Further research is required to increase the confidence in these results. Abbreviations PPD : Peripartum depression MDD : Major depressive disorder ECT : Electroconvulsive therapy MAO : Monoamine oxidase rTMS : Repeated transcranial magnetic stimulation DLPFC : Dorsolateral prefrontal cortex RCT : Randomized controlled trial NRS : Non-randomized studies DSM-5 : Diagnostic and Statistical Manual of Mental Disorders-5 HDRS : Hamilton Depression Rating Scale ROB2 : Risk of bias 2 ROBINS-I : The Risk of Bias Assessment tool for Nonrandomized Studies SMD : Standardized Mean Deviation CI: confidence interval MARDS : Montgomery-Åsberg Depression Rating Scale BDI: Beck Depression Inventory. EPDS : Edinburgh Postnatal Depression Scale QALY : Quality adjusted life year CGI-S : Clinical Global impression scale GAS : Global Assessment Scale SF-36-V : 36-item Quality of Life Health Survey Vitality scores SF-36-MH : 36-item Quality of Life Health Survey Mental Health scores Declarations Acknowledgements We would like to thank the Korea Health Industry Development Institute(KHIDI) for supporting the training program for advanced medical device industry professionals. Availability of data and materials No data or materials were generated for this narrative review. Authors' information Affiliations Department of Medical Devices Industry, Dongguk University-Seoul (04620) 30, Pildong-ro 1 –gil, Jung-gu, Seoul, Republic of Korea Hyune June Lee, Sung Min Kim, Ji Yean Kwon Authors contributions HJ: Conceive the project, search strategy, screening literature, data extraction, bias evaluation, data analysis, and drafting the manuscript and revising. SM: supervised the entire procedures and helped to draft the manuscript. JY: Study design, screening literature, bias evaluation, data analysis, drafting the manuscript, and revising the manuscript. All authors read and approved the final manuscript. Corresponding author Correspondence to Ji Yean Kwon( [email protected] ) Funding No funding was obtained for this study. Ethics approval and consent to participate Not applicable Consent for publication Not applicable Competing interests The authors declare that they have no competing interest Supplementary information Appendix 1 searching strategy.docx : How to searching using terms or mesh 2.Appendix 2 excluded studies.docx : Excluded literature and the reason 3.Appendix 3 risk of bias assessment.docx : Risk assessment of selected literature 4.Appendix 4 PRISMA checklist.docx : PRISMA checklist References Association D-AP: Diagnostic and statistical manual of mental disorders . 2013. 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Arch Pediatr Adolesc Med 2011, 165 (10):945-950. Allen CH, Kluger BM, Buard I: Safety of Transcranial Magnetic Stimulation in Children: A Systematic Review of the Literature . Pediatr Neurol 2017, 68 :3-17. Yanamadala J, Noetscher GM, Makarov SN, Pascual-Leone A: Estimates of peak electric fields induced by Transcranial magnetic stimulation in pregnant women as patients using an FEM full-body model . In: 2017 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC): 11-15 July 2017 2017 ; 2017: 1441-1444. O'Mahen HA, Flynn HA: Preferences and perceived barriers to treatment for depression during the perinatal period . Journal of women's health 2008, 17 (8):1301-1309. Goodman JH: Women’s attitudes, preferences, and perceived barriers to treatment for perinatal depression . Birth 2009, 36 (1):60-69. Cepeda MS, Kern DM, Nicholson S: Treatment resistant depression in women with peripartum depression . BMC Pregnancy and Childbirth 2019, 19 (1):323. Maughan D, Molodynski A: An international perspective on the acceptability and sustainability of electroconvulsive therapy . BJPsych Int 2016, 13 (1):10-12. Kim DR, Sockol L, Barber JP, Moseley M, Lamprou L, Rickels K, O'Reardon JP, Epperson CN: A survey of patient acceptability of repetitive transcranial magnetic stimulation (TMS) during pregnancy . Journal of affective disorders 2011, 129 (1-3):385-390. Simpson KN, Welch MJ, Kozel FA, Demitrack MA, Nahas Z: Cost-effectiveness of transcranial magnetic stimulation in the treatment of major depression: a health economics analysis . Advances in therapy 2009, 26 (3):346-368. Zhao YJ, Tor PC, Khoo AL, Teng M, Lim BP, Mok YM: Cost‐Effectiveness Modeling of Repetitive Transcranial Magnetic Stimulation Compared to Electroconvulsive Therapy for Treatment‐Resistant Depression in Singapore . Neuromodulation: Technology at the Neural Interface 2018, 21 (4):376-382. Lancaster CA, Gold KJ, Flynn HA, Yoo H, Marcus SM, Davis MM: Risk factors for depressive symptoms during pregnancy: a systematic review . American journal of obstetrics and gynecology 2010, 202 (1):5-14. Supplementary Files Appendix1Searchingstrategy.docx Appendix2Excludedstudies.docx Appendix3Riskofbiasassessment.docx Appendix4PRISMAchecklist.doc Cite Share Download PDF Status: Published Journal Publication published 09 Feb, 2021 Read the published version in BMC Pregnancy and Childbirth → Version 1 posted Editorial decision: Minor revision 30 Dec, 2020 Review # 2 received at journal 29 Dec, 2020 Review # 1 received at journal 17 Dec, 2020 Reviewer # 2 agreed at journal 29 Nov, 2020 Reviewer # 1 agreed at journal 28 Nov, 2020 Reviewers invited by journal 18 Nov, 2020 Editor assigned by journal 08 Nov, 2020 Submission checks completed at journal 08 Nov, 2020 Editor invited by journal 08 Nov, 2020 First submitted to journal 03 Nov, 2020 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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BDI: Beck Depression Inventory; CGI-S: Clinical Global \nImpression Scale; EPDS: Edinburgh Postnatal Depression Scale; HDRS: Hamilton Depression \nRating Scale; GAS, Global Assessment Scale; SF-36-V and SF-36-MH: 36-item Quality of Life \nHealth Survey, Vitality, and Mental Health scores; IDS-SR: Inventory of Depressive \nSymptomatology-Self-Report.","description":"","filename":"Figure.3Forestplotoftherapeuticeffect.png","url":"https://assets-eu.researchsquare.com/files/rs-108764/v1/69079e7e93374dd2a754e1b4.png"},{"id":3697618,"identity":"71c90254-8ef4-4c30-a93f-70482e867c2b","added_by":"auto","created_at":"2020-11-19 16:19:56","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":391002,"visible":true,"origin":"","legend":"Forest plot of the sensitivity analysis.\nAbbreviations: BAI: Beck Anxiety Inventory; BDI: Beck Depression Inventory; CGI-S: Clinical Global \nImpression Scale; EPDS: Edinburgh Postnatal Depression Scale; HDRS: Hamilton Depression \nRating Scale; GAS, Global Assessment Scale; SF-36-V and SF-36-MH: 36-item Quality of Life \nHealth Survey, Vitality, and Mental Health scores.","description":"","filename":"Figure.4Forestplotofthesensitivityanalysis.png","url":"https://assets-eu.researchsquare.com/files/rs-108764/v1/8312b5c565ab99723407de62.png"},{"id":3697619,"identity":"1e7f80f8-8080-4eeb-9da6-db0fc943c7b1","added_by":"auto","created_at":"2020-11-19 16:19:56","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":265224,"visible":true,"origin":"","legend":"Forest plot of the side effects","description":"","filename":"Figure.5Forestplotofsideeffect.png","url":"https://assets-eu.researchsquare.com/files/rs-108764/v1/77c14716e669c28bd20b0664.png"},{"id":3697620,"identity":"b3bfd175-d924-42fb-b1fb-e3f874ef7516","added_by":"auto","created_at":"2020-11-19 16:19:56","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":887289,"visible":true,"origin":"","legend":"Risk of bias graphs: (a) RCT risk of bias, (b) NRS risk of bias, and (c) case study risk of bias","description":"","filename":"Figure.6Riskofbias.jpg","url":"https://assets-eu.researchsquare.com/files/rs-108764/v1/4bfaf1ca8ee950b1b30b1b55.jpg"},{"id":3697621,"identity":"53842fc3-840c-4b8b-a409-f1ffb37f71a6","added_by":"auto","created_at":"2020-11-19 16:19:57","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":35890,"visible":true,"origin":"","legend":"Funnel plot","description":"","filename":"Figure.7Funnelplot.PNG","url":"https://assets-eu.researchsquare.com/files/rs-108764/v1/3bf10ba6f4ef6b48994d66ad.PNG"},{"id":13616732,"identity":"fd9331f4-a68f-473a-bf26-99a3af5ad952","added_by":"auto","created_at":"2021-09-17 06:50:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3254022,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-108764/v1/dfdf67e0-8ea4-4cee-bf33-1a03a52f3922.pdf"},{"id":3697622,"identity":"11a2808c-b5dc-48b9-9627-ade6711bc31b","added_by":"auto","created_at":"2020-11-19 16:19:57","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":15786,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix1Searchingstrategy.docx","url":"https://assets-eu.researchsquare.com/files/rs-108764/v1/318efe6fe2964327496b634e.docx"},{"id":3697623,"identity":"49d5252c-5b13-4686-9c3b-3ed2cc1e2548","added_by":"auto","created_at":"2020-11-19 16:19:57","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":17677,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix2Excludedstudies.docx","url":"https://assets-eu.researchsquare.com/files/rs-108764/v1/a943aa71a2c418f5b6ee5b9e.docx"},{"id":3697624,"identity":"5f41991a-99d0-48b8-aa32-5e3e9a48fb16","added_by":"auto","created_at":"2020-11-19 16:19:57","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":68038,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix3Riskofbiasassessment.docx","url":"https://assets-eu.researchsquare.com/files/rs-108764/v1/18dbd66cabd7d9dd1917d6f2.docx"},{"id":3697625,"identity":"f272e447-f815-4997-b7e2-2e8a78547532","added_by":"auto","created_at":"2020-11-19 16:19:58","extension":"doc","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":66048,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix4PRISMAchecklist.doc","url":"https://assets-eu.researchsquare.com/files/rs-108764/v1/45cd2dfc567aff80ce7820bc.doc"}],"financialInterests":"","formattedTitle":"\u003cp\u003eRepetitive Transcranial Magnetic Stimulation Treatment for Peripartum Depression: Systematic Review \u0026amp; Meta-Analysis\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003ePeripartum depression (PPD) is defined as major depression occurring within the gestational period and four weeks after childbirth. [1]. PPD is a common disease that 10 \u0026ndash; 20% of pregnant women experience [2], and PPD patients incur a massive lifetime expense of 75,728 pounds (USD $95,656) [3]. PPD threatens not only the mother\u0026rsquo;s health by causes hormonal imbalance [4], alcohol and substance abuse [5], and increases maternal suicide [6]. The health of the fetus is also affected by premature birth [7] and low birth weight [8]. PPD also interferes with creating a stable attachment in the growth process of infants, which can result in self-control and cognitive function behavioral issues [9].\u003c/p\u003e\n\u003cp\u003eThe methods for treating PPD are mainly electroconvulsive therapy (ECT) and antidepressants [10]. Although both of them have proven treatment effectiveness for PPD [11-14], some concerns for the safety of pregnant women and fetuses have been raised. Antidepressants relieve depression by regulating the neurotransmitters that make people feel happy [15]. Neurotransmitters released from pre-synaptic neurons are reabsorbed or decomposed by monoamine oxidase enzymes in the process of transferring them to the neurons from the synapses. Antidepressants reduce neurotransmitter decomposition by interfering with their reabsorption and the activity of monoamine oxidase enzymes, thereby alleviating depression [16]. Antidepressants are one of the most used treatment methods for PPD, but there are some concerns. Because components of antidepressants can pass through the placenta [17], these could have a chemical effect on the fetus. Pregnant women taking antidepressants have a 7-fold increased risk of spontaneously induced abortion [18, 19], a more than 3-fold increased risk of fetal infections [20], and increased risks of premature birth and underweight babies [21], autism spectrum disorder in the baby [22], increased risk of motor, speech, and scholastic disorder [23], cardiac defects [24] and persistent pulmonary hypertension [25]. Also, infants can be exposed to antidepressants and their metabolites during breastfeeding [26], which could increase monoamine oxidase levels and affect the functional maturity of the infant\u0026rsquo;s brain [27]. Side effects such as decreased feeding [28], colic, and irritability [29] have been reported. Another treatment, ECT, is a method of delivering a stimulating electrical shock to the brain to relieve depression. Electric shocks affecting neurons and chemicals in the brain produce short and controlled seizures, which have excellent effects on various neurological disorders [30]. However, treating pregnant women with ECTs can cause adverse effects such as vaginal bleeding and miscarriage [31], uterine contractions [32], abdominal pain [33], and preeclampsia [34]. Clinicians recommend these treatments because the risk of the treatment is smaller than the risk of PPD [35, 36] and their effectiveness has been proven. However, considering the safety concerns of these treatments for the fetus and mother, research to identify safer treatment methods is needed.\u003c/p\u003e\n\u003cp\u003eWith the recent development in brain stimulation research, many researchers are increasingly trying to use brain stimulation for various neurological treatments [37]. One type of brain stimulation, repetitive transcranial magnetic stimulation (rTMS) stimulates the brain\u0026rsquo;s dorsolateral prefrontal cortex (DLPFC) with magnetic fields to induce the degeneration of neurons and activate the neural system of the brain to relieve depression [38]. Using rTMS to treat PPD is still reluctant [39-41], although studies have shown that rTMS is safe [42] and effective for treating several neurological diseases [43-45].\u003c/p\u003e\n\u003cp\u003eThus, in this paper, we conducted a systematic review and meta-analysis to confirm whether rTMS treatment was suitable for PPD. There are few systematic review studies on rTMS treatment for PPD [46-49], but no studies statistically analyzed the therapeutic effects and safety and considered the adverse effects on fetuses. To investigate these problems, we conducted a meta-analysis to confirm the effect size of the therapeutic effects and safety and extended the range of patients from pregnant patients to one year after childbirth to identify the effect on the fetuses.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe systematic review followed the PRISMA guidelines (registration number CRD42020197855).\u003c/p\u003e\n\u003cp\u003eKey questions\u003c/p\u003e\n\u003cp\u003eThe criteria used in selecting the relevant studies included patients from the pregnancy period to one year after childbirth, intervention with TMS; no limits on the comparators, and outcomes measured by the degree of depression alleviation. The detailed key questions were:\u003c/p\u003e\n\u003cp\u003e(1) Is rTMS effective for PPD? What is the effect size of rTMS for PPD?\u003c/p\u003e\n\u003cp\u003e(2) Does rTMS have maternal and fetal side effects? What is the effect size of the side effects caused by rTMS?\u003c/p\u003e\n\u003cp\u003eInclusion and exclusion criteria\u003c/p\u003e\n\u003cp\u003eIn general, the studies used for the meta-analysis were randomized controlled trials (RCTs), but, non-randomized studies (NRS) were also included in the meta-analysis, and case studies were included in the systematic review because only a small number of randomized trials provided evidence of the effects of the interventions [50] associated with pregnancy. Before inclusion, the non-randomized studies were evaluated to verify that the patients, interventions, comparisons, and outcomes were set appropriately by the Cochrane algorithm. If systematic reviews or meta-analyses were included, we checked the included studies and references. The criteria for exclusion were (1) experimental studies with animals, (2) studies not published in English, (3) studies that were not original (if there was only abstract, the original text was requested in an e-mail to the author), (4) symptoms of baby blues or postpartum psychosis, and (5) major depressive disorder that did not occur from pregnancy to one year after childbirth.\u003c/p\u003e\n\u003cp\u003eLiterature search strategy\u003c/p\u003e\n\u003cp\u003eWe performed a literature search of studies published before the end of September 2020 using EMBASE, MEDLINE, PsycINFO, and the Cochrane Library. In the literature search, the medical indications and treatment methods were searched using Boolean models. The indications search terms were peripartum depression or antepartum depression or postpartum depression or pregnancy or perinatal, and the treatment searches used rTMS or repeated transcranial magnetic stimulation or TMS or transcranial magnetic stimulation. The detailed search strategies are presented in Appendix 1. To minimize the omission of data and increase the reliability, two researchers independently reviewed the literature and, if the opinions of the researchers differed, the studies were reviewed together and an agreement was reached.\u003c/p\u003e\n\u003cp\u003eData extraction\u003c/p\u003e\n\u003cp\u003eThe data extraction items for the studies that were finally selected through the literature screening included the characteristics of the study design, demographic characteristics, the characteristics of the treatment effect variables known to affect treatment effectiveness [51], and the characteristics of the effects on the mother and fetus. The details are presented in Figure 1.\u003c/p\u003e\n\u003cp\u003eRisk of bias assessment\u003c/p\u003e\n\u003cp\u003eAfter the literature screening, a bias evaluation of the studies was performed by two evaluators independently to clarify ambiguous differences between the reporting quality and research quality. Different evaluation methods were applied according to the study design. RCT studies were examined using the risk-of-bias 2 (ROB2) tool [52] and the NRS were examined using the Risk of Bias Assessment Tool for Non-randomized Studies (ROBINS-I) [53]. Case reports and series were evaluated used the methodological quality tool [54] because they could be adopted as evidence of new treatments [55]. The final judgment on the overall risk of bias was agreed upon between the two evaluators and publication bias was visually reviewed through funnel plots, and additionally, statistically confirmed through Egger's regression.\u003c/p\u003e\n\u003cp\u003eData analysis\u003c/p\u003e\n\u003cp\u003eData analysis was conducted using Comprehensive Meta-Analysis 3 software (CMA3). The effect size was used standardized mean difference (SMD) was obtained using two-group, pre-post data in the RCTs, and one group pre-post data for the NRS [56]. For the 95% CI and the correlation coefficient value of 0.5, the generic inverse variance estimation method was used [57]. Safety was assessed using the effect size of the side effects and the effect size was calculated by the same method as the treatment effect. The calculations are presented as a Forest plot. Heterogeneity was determined using the statistical test method Cochrane's Q test and the I-squared (I\u0026sup2;) statistic. If the \u003cem\u003ep\u003c/em\u003e-value of the Q test value exceeded 0.1 and the I\u0026sup2; statistic exceeded 50%, a random-effects model was applied, and if the Q test value was less than 0.1 and the I\u0026sup2; statistic was less than 50%, a fixed-effects model was applied.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eSearch results\u003c/p\u003e\n\u003cp\u003eWe conducted a literature search following the PRISMA FLOW guidelines. Of the 229 studies identified in the database, 128 remained after the removal of the duplicates. Ninety-eight studies were excluded because they did not meet the inclusion and exclusion criteria. We performed a full-text review of 30 studies to confirm whether they were suitable for our research purposes. Finally, 11 studies suitable for the systematic review and five studies suitable for meta-analysis were selected to confirm the therapeutic effect and safety of rTMS. There were three studies with only abstracts, so we requested the original text by email, but no author responded.\u003c/p\u003e\n\u003cp\u003eCharacteristics of the selected studies\u003c/p\u003e\n\u003cp\u003eEleven studies identified the efficacy and safety of rTMS for PPD, two RCT studies [58, 59], four NRS [60-63], and five case studies [63-67]. One NRS study was excluded from the meta-analysis since the study did not report detailed outcomes. The total number of participants was 101, 84 of whom received active rTMS treatment. During pregnancy, 65 patients were treated with rTMS, and most of them were in the second and third trimesters of pregnancy. Seventeen patients were treated for postpartum depression, and two patients were treated during pregnancy and after delivery. Although 20 participants were treated with antidepressants [60, 62, 65, 68] along with rTMS, their antidepressant doses were stable for two to four weeks, and one participant was treated with clonazepam for insomnia [61]. The treatment parameters and protocols in each study were all different, which seemed to be because the protocol for TMS therapy for perinatal depression has not yet been accurately established. Twenty-two patients were stimulated to the right DLPFC [58, 60, 65, 66], 79 to the left DLPFC [59, 61-65, 69], and the patients in two studies [65, 68] were stimulated on both sites. The patients who were stimulated on the right DLPFC showed symptoms of anxiety and were treated with a frequency of less than 1 Hz, which is relatively less than that used to stimulate the left DLPFC (more than 5 Hz). The researchers considered the interval time and duration of stimulation to minimize side effects such as seizures and did not show any common characteristics for the other treatment parameters.\u003c/p\u003e\n\u003cp\u003eTable 1 Characteristics of the subjects in the included studies\u003c/p\u003e\n\u003ctable border=\"1\" width=\"100%\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e\u003cstrong\u003eStudy\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e\u003cstrong\u003eSubjects\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e\u003cstrong\u003eGestational age\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e\u003cstrong\u003ePsychiatric diagnosis\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e\u003cstrong\u003eSimultaneous treatment\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"14%\"\u003e\n\u003cp\u003eD. R. Kim et al., 2019 [58]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"16%\"\u003e\n\u003cp\u003eRandomized\u003c/p\u003e\n\u003cp\u003econtrolled trial\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003eActive 11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e30.13 \u0026plusmn; 5.78\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e22.19 \u0026plusmn; 7.11\u003c/p\u003e\n\u003cp\u003e(Weeks)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"12%\"\u003e\n\u003cp\u003eMDD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"17%\"\u003e\n\u003cp\u003eFree\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003eSham 11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e26.41 \u0026plusmn; 5.11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e25.62 \u0026plusmn; 7.61\u003c/p\u003e\n\u003cp\u003e(Weeks)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"14%\"\u003e\n\u003cp\u003eMyczkowski et al., 2012 [59]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"16%\"\u003e\n\u003cp\u003eDouble-blind randomized\u003c/p\u003e\n\u003cp\u003econtrolled trial\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003eActive 8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e29.63 \u0026plusmn; 6.37\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e4.13 \u0026plusmn; 2.85\u003c/p\u003e\n\u003cp\u003e(Month)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"12%\"\u003e\n\u003cp\u003eMDD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"17%\"\u003e\n\u003cp\u003eFree\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003eSham 6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e26.67 \u0026plusmn; 7.15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e3.50 \u0026plusmn; 2.74\u003c/p\u003e\n\u003cp\u003e(Month)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eD. R. Kim et al., 2011 [60]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003eNon-randomized\u003c/p\u003e\n\u003cp\u003econtrolled trial\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e31.2 \u0026plusmn; 5.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e25.8 \u0026plusmn; 5.16\u003c/p\u003e\n\u003cp\u003e(weeks)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eMDD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e4 patients treated\u003c/p\u003e\n\u003cp\u003ewith antidepressants\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eHizli Sayar et al., 2014 [62]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003eNon-randomized\u003c/p\u003e\n\u003cp\u003econtrolled trial\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e32.69 \u0026plusmn; 3.69\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e14.26 \u0026plusmn; 8.25\u003c/p\u003e\n\u003cp\u003e(weeks)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eMDD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e12 patients treated\u003c/p\u003e\n\u003cp\u003ewith antidepressants\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eGarcia et al., 2010 [61]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003eNon-randomized\u003c/p\u003e\n\u003cp\u003econtrolled trial\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e34.11 \u0026plusmn; 6.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eAfter birth\u003c/p\u003e\n\u003cp\u003e30 days to\u003c/p\u003e\n\u003cp\u003e1 year\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eMDD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003eFree\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eTarhan et al., 2012 [69]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003eNon-randomized\u003c/p\u003e\n\u003cp\u003econtrolled trial\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eMDD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eZhang et al., 2010 [64]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003eCase report\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e28\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003cp\u003e(weeks)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eMDD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003eFree\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eTan et al., 2008 [63]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003eCase report\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eFrom 0 to postpartum period\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eMDD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003eFree\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"14%\"\u003e\n\u003cp\u003eFerra\u0026tilde;o et al., 2018 [65]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"16%\"\u003e\n\u003cp\u003eCase report\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e3 (Left)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e35.7 \u0026plusmn; 2.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e6.67 \u0026plusmn; 3.06\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"12%\"\u003e\n\u003cp\u003eMDD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e2 patients treated\u003c/p\u003e\n\u003cp\u003ewith antidepressants\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e1 (Right)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e1 patient treated\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;with antidepressants\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eCohen et al., 2008 [66]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003eCase report\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eUntil 20\u003c/p\u003e\n\u003cp\u003e(weeks)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eMDD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003eFree\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"14%\"\u003e\n\u003cp\u003eMonika Kl\u0026iacute;rov\u0026aacute; et al [67]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"16%\"\u003e\n\u003cp\u003eCase report\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e1 (Left)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eMDD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003eTreated with antidepressant\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e1 (Right)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e31\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eMDD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003eTreated with antidepressant\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*MDD: major depressive disorder\u003c/p\u003e\n\u003cp\u003eTable 2 Characteristics of the treatments in the included studies\u003c/p\u003e\n\u003ctable border=\"1\" width=\"100%\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e\u003cstrong\u003eStudy\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003e\u003cstrong\u003eMotor\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ethreshold\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e\u003cstrong\u003eSite of\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003estimulation\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e\u003cstrong\u003eFrequency\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e\u003cstrong\u003eNumber of pulses\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e\u003cstrong\u003eInter-event\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003einterval\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003e\u003cstrong\u003eNumber of Sessions\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eD. R. Kim et al., 2019 [58]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003e100%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eRight DLPFC*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e1-Hz\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e900\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e60 s** on\u003c/p\u003e\n\u003cp\u003e60 s off\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eMyczkowski et al., 2012 [59]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003e120%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eLeft DLPFC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e5-Hz\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e1250\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e10 s on\u003c/p\u003e\n\u003cp\u003e20 s off\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eD. R. Kim et al., 2011 [60]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003e100%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eRight DLPFC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e1-Hz\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e300\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e60 s on\u003c/p\u003e\n\u003cp\u003e60 s off\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eHizli Sayar et al., 2014 [62]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003e100%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eLeft DLPFC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e25-Hz\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e1000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e2 s on\u003c/p\u003e\n\u003cp\u003e30 s off\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eGarcia et al., 2010 [61]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003e120%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eLeft DLPFC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e10-Hz\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e150\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e4 s on\u003c/p\u003e\n\u003cp\u003e26 s off\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eTarhan et al., 2012 [69]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003e100%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eLeft DLPFC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e25-Hz\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e1000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e2 s on\u003c/p\u003e\n\u003cp\u003e30 s off\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eZhang et al., 2010 [64]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003e90%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eLeft DLPFC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e1-Hz\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e1200\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e20 s off\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003e42\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eTan et al., 2008 [63]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003e110%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eLeft DLPFC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e25-Hz\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e1000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e2 s on\u003c/p\u003e\n\u003cp\u003e28 s off\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003e77\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"14%\"\u003e\n\u003cp\u003eFerra\u0026tilde;o et al., 2018 [65]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"16%\"\u003e\n\u003cp\u003e120%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eLeft DLPFC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e10-Hz\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e3000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"14%\"\u003e\n\u003cp\u003e*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003e42.67\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eRight DLPRC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e1-Hz\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e1800\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eCohen et al., 2008 [66]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"16%\"\u003e\n\u003cp\u003e110%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eRight DLPFC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e1-Hz\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e1600\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"14%\"\u003e\n\u003cp\u003eMonika Kl\u0026iacute;rov\u0026aacute; et al [67]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"16%\"\u003e\n\u003cp\u003e100%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eLeft DLPFC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e20-Hz\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e2000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e2 s on\u003c/p\u003e\n\u003cp\u003e30 s off\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003eRight DLPRC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e1-Hz\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e300\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e60 s on\u003c/p\u003e\n\u003cp\u003e60 s off\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e* DLPFC: dorsolateral prefrontal cortex; s, seconds\u003c/p\u003e\n\u003cp\u003eTable 3 Characteristics of the outcomes in the included studies\u003c/p\u003e\n\u003ctable border=\"1\" width=\"113%\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003e\u003cstrong\u003eStudy\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e\u003cstrong\u003eInstrument\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e\u003cstrong\u003ePre-TMS****\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e\u003cstrong\u003ePost-TMS\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"10%\"\u003e\n\u003cp\u003e\u003cstrong\u003eRemission\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e\u003cstrong\u003eResponse\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e\u003cstrong\u003eSide effects (mother)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003e\u003cstrong\u003eInfants\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"13%\"\u003e\n\u003cp\u003eD. R. Kim et al., 2019 [58]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"11%\"\u003e\n\u003cp\u003eHDRS-17*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e23.18 \u0026plusmn; 3.54\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e9.27 \u0026plusmn; 6.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"10%\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"14%\"\u003e\n\u003cp\u003e1 patient had a headache\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"15%\"\u003e\n\u003cp\u003e3 preterm births\u003c/p\u003e\n\u003cp\u003e1 shoulder dystocia\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e22.27 \u0026plusmn; 2.65\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e13.18 \u0026plusmn; 8.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"10%\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"13%\"\u003e\n\u003cp\u003eMyczkowski et al., 2012 [59]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"11%\"\u003e\n\u003cp\u003eHDRS-17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e29.13 \u0026plusmn; 5.64\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e18.50 \u0026plusmn; 9.83\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"10%\"\u003e\n\u003cp\u003e*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"9%\"\u003e\n\u003cp\u003e*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"14%\"\u003e\n\u003cp\u003e2 patients had a mild headache\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"15%\"\u003e\n\u003cp\u003e*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e26.67 \u0026plusmn; 5.68\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e24.83 \u0026plusmn; 7.60\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003eD. R. Kim et al., 2011 [60]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003eHDRS-17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e24.4 \u0026plusmn; 5.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e9.7 \u0026plusmn; 6.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"10%\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e4 patients had a mild headache.\u003c/p\u003e\n\u003cp\u003e1 patient had an episode of supine hypotension\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003eAll infants were in the well-baby nursery\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003eHizli Sayar et al., 2014 [62]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003eHDRS-17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e26.67 \u0026plusmn; 5.58\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e13.03 \u0026plusmn; 6.93\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"10%\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003eshowed any\u003c/p\u003e\n\u003cp\u003eabnormalities.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003eGarcia et al., 2010 [61]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003eHDRS-24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e22.67 \u0026plusmn;6.44\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e2.14 \u0026plusmn; 3.19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"10%\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eHeadache,\u003c/p\u003e\n\u003cp\u003esite pain\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003e*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003eTarhan et al., 2012 [69]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003eHDRS-17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"10%\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003eAll had healthy babies\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003eZhang et al., 2010 [64]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003eHDRS-24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"10%\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003eHealthy boy\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003eTan et al.,\u003c/p\u003e\n\u003cp\u003e2008 [63]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003eHDRS-17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e38\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"10%\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003eNo diagnosis of disease\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"13%\"\u003e\n\u003cp\u003eFerra\u0026tilde;o et al., 2018 [65]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"11%\"\u003e\n\u003cp\u003eHDRS-21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e24.33 \u0026plusmn; 5.24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e7.33 \u0026plusmn; 4.03\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"10%\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e2 patients had discomfort at the application site.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"15%\"\u003e\n\u003cp\u003ePreterm twins\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"10%\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003eDiscomfort at the application site and sore throat\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"13%\"\u003e\n\u003cp\u003eCohen et al., 2008 [66]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003eHDRS-17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"10%\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"14%\"\u003e\n\u003cp\u003e*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"15%\"\u003e\n\u003cp\u003eThe infant had normal neurologic development\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"13%\"\u003e\n\u003cp\u003eMonika Kl\u0026iacute;rov\u0026aacute; et al., 2008 [67]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003eMADRS**\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"10%\"\u003e\n\u003cp\u003e*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"14%\"\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"15%\"\u003e\n\u003cp\u003eHealthy baby\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003eBDI***\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"12%\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"10%\"\u003e\n\u003cp\u003e*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e* HDRS: Hamilton Depression Rating Scale (HDRS-21,24 is an expanded version of the HDRS-17)\u003c/p\u003e\n\u003cp\u003e** MARDS: Montgomery-\u0026Aring;sberg Depression Rating Scale\u003c/p\u003e\n\u003cp\u003e*** BDI: Beck Depression Inventory\u003c/p\u003e\n\u003cp\u003e**** TMS: transcranial magnetic stimulation\u003c/p\u003e\n\u003cp\u003eTherapeutic effects\u003c/p\u003e\n\u003cp\u003eIn the 11 studies selected for the systematic literature review, except for the study by Tarhan [69], which did not report the detailed treatment effects of rTMS, 76 patients had an average 59% improvement in depression. Thirty-seven percent of the participants showed depression remission (depression scale rating was lowered to that of a normal person), and 66% of the participants showed a response to rTMS (depression scale score reduced more than 50% compared to before treatment). In Kim's study [67], one of the RCT studies, 45.45% of the control group responded, whereas 81% of the experimental group responded, and the remission rate also showed a significant difference of 9% or more between the experimental group and the control group. Another RCT study also showed a difference in the depression scale of about 23% between the control group and the experimental group, showing a similar treatment effect to that of antidepressants [59]. In the NRS, the response rate of 56 participants was 33%, and the remission rate was 59%. In the study by Garcia et al. [61], the depression scale scores showed that all participants achieved remission, and all except one participant responded to rTMS. The other NRS also showed treatment effects, and in the case study, all nine participants responded to rTMS. All studies showed treatment effectiveness, but treatment effectiveness declined as the study design was refined.\u003c/p\u003e\n\u003cp\u003eEvaluation of the heterogeneity of the studies for treatment effects showed a \u003cem\u003ep-\u003c/em\u003evalue of \u0026lt; 0.001 and an \u003cem\u003eI\u0026nbsp;\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e statistic of 71.933. Because the \u003cem\u003eI\u0026nbsp;\u003c/em\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e statistic exceeded 50%, a random-effects model was applied. The effect size of rTMS for PPD had an SMD of 1.394 (95% CI: 0.920 \u0026ndash; 1.843), indicating a significant treatment effect (Z = 6.079, p \u0026lt; 0.01).\u003c/p\u003e\n\u003cp\u003eFigure 3 shows the sensitivity analysis performed because we thought that the treatment effect in one study [61] was measured too high. Excluding this, the heterogeneity showed a \u003cem\u003ep-\u003c/em\u003evalue of\u003cem\u003e \u0026lt; 0.01\u003c/em\u003e and an \u003cem\u003eI\u003c/em\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e statistic of 62.593, and because the \u003cem\u003eI\u003c/em\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e value exceeded 50%, a random-effects model was applied. The effect size of rTMS for PPD had an SMD of 1.074 (95% CI: 0.777 \u0026ndash; 1.233), indicating a meaningful treatment effect \u003cem\u003e(\u003c/em\u003eZ = 5.468\u003cem\u003e, p \u003c/em\u003e\u0026lt; 0.01\u003cem\u003e)\u003c/em\u003e. The sensitivity analysis showed that the heterogeneity decreased, but the \u003cem\u003eI\u003c/em\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e value still exceeded 50%, and the treatment effect was also slightly reduced, but the treatment effect was still significant.\u003c/p\u003e\n\u003cp\u003eSafety\u003c/p\u003e\n\u003cp\u003eIn the 11 studies selected for systematic review, about 15% of the patients experienced side effects in the group receiving rTMS therapy. However, in the RCTs, there was no difference between the experimental groups and the control groups [58, 59], and there were minor side effects that did not worsen the patients\u0026rsquo; health, such as headache [58, 60, 61, 65, 66] and pain at the stimulation site [61, 66]. Supine hypotension syndrome was reported as an adverse event in some mothers [60]. However, this is a disorder caused by posture during treatment and can be prevented after posture correction [70]. The side effects in the infants included preterm birth, and five fetuses experienced preterm birth, but all of the fetuses were healthy. Brachial plexus injury was reported as an adverse event in one fetus, but it was caused by the large shoulder of the fetus and was not a side effect of the treatment process [58].\u003c/p\u003e\n\u003cp\u003eEvaluation of the heterogeneity of the studies for the side effects showed a\u003cem\u003e p\u003c/em\u003e-value of \u0026lt; 0.01 and an \u003cem\u003eI\u003c/em\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e value of 46.631 and, because the \u003cem\u003eI\u003c/em\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e value was less than 50%, a fixed-effects model was applied. The effect size of side effects had an SMD of 0.346, (95% CI\u003cem\u003e:\u003c/em\u003e 0.214 \u0026ndash; 0.506), indicating that rTMS had an effect on the occurrence of side effects (Z = -1.889, p = 0.059).\u003c/p\u003e\n\u003cp\u003eRisk of bias\u003c/p\u003e\n\u003cp\u003eAccording to the experimental design, the RCTs were evaluated by ROB2, the NRS by ROBIN-I, and the case studies were evaluated using a methodological quality tool. We evaluated the bias according to the guidance of the tool and assessed the overall bias as a low risk of bias if all domains of bias were low risk, a high risk of bias if there were one or more high-risk domains or many suspected risks. In the case of Myczkowski\u0026rsquo;s study [59], the study could have selective reporting bias because the planned outcomes were selectively reported. Bias in the outcomes measurements in the NRS was evaluated as moderate [60-63] because the study design of all of the NRS was open-label, meaning that the patients knew their treatment, and the risk of bias in Garcia\u0026rsquo;s study [61] was evaluated as high because there were missing data, which could have a significant impact on the outcome. The overall evaluation of bias was moderate, but this must be considered as it can cause over or underestimation of the effect sizes. The detailed risk of bias assessment for the domains is presented in Appendix 3.\u003c/p\u003e\n\u003cp\u003eFigure 7 is a funnel plot showing the relationship between the sample size and the effect size to confirm publication bias. We visually checked whether the funnel plot was symmetrical and checked Egger's regression to determine statistically significant. Publication bias existed because the funnel plot was not symmetric and had a \u003cem\u003ep\u003c/em\u003e-value of 0.01. However, without Garcia's study [61], which had a high risk of bias, the funnel plot had a symmetrical structure and a \u003cem\u003ep\u003c/em\u003e-value of 0.121, so it can be said that there was no publication bias. In the case of safety, since there were fewer than 10 documents included, the minimum conditions for publication bias were not satisfied, and the publication bias of the side effects was not analyzed.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe effect size of the therapeutic effect had an SMD of 1.394 (95% CI: 0.920 \u0026ndash; 1.843), which was significant for treating depression [71] and except for Garcia\u0026rsquo;s study [61], in which reporting bias was suspected because of the selection reporting, the effect size SMD was 1.074, (95% CI: 0.777 \u0026ndash;1.233), which was also a meaningful result. The studies excluded by the exclusion criteria also showed positive treatment effects of rTMS for PPD, supporting the treatment effect. In Brock's study, 14 out of 19 patients with rTMS achieved remission [72], and in Ozmut's study, eight out of 15 patients responded to rTMS [73]. Other studies also succeeded in improving the depression of patients with PPD using rTMS [74, 75]. It could be possible that the effect size was overestimated because the parameters that can affect the treatment effect, such as the site of stimulation, frequency, and interval time, were not established, and there was a risk of bias. However, even considering these points, the treatment potential was confirmed, and if a protocol becomes established, it is expected that more sophisticated effect sizes can be calculated.\u003c/p\u003e\n\u003cp\u003eThe effect size of TMS side effects had an SMD of 0.346 (95% CI: 0.214 \u0026ndash; 0.506), which was significant [71]. However, the side effects of rTMS treatment on the mothers, such as headaches, discomfort, and pain in the stimulation area were minor, and these side effects disappeared at the end of the treatment process.. Some mothers experienced supine hypotension [60], but this was caused by a posture problem during treatment and could be prevented through postural correction [70].\u003c/p\u003e\n\u003cp\u003eAll children born to mothers with rTMS treatment were born healthy. In one of the RCT studies that evaluated the child\u0026rsquo;s health condition by appearance-pulse-grimace-activity-respiration scores, the difference between the two groups was not significant [experimental group 8.36 (1.50), control group 8.73 (0.90), p = 0.501] [58]. There were five preterm births and one brachial plexus injury among the fetuses. Although 5% (5) of the study participants experienced preterm birth, two of these had already been warned of the risk of preterm birth by a biomedical test. Considering that the average proportion of women who undergo preterm birth worldwide is 9.1 to 13.4% [76], it is unlikely that a causal relationship exists between rTMS and preterm birth. However, further research on this is needed. Brachial plexus injury was reported as a side effect in one newborn, but it was not related to rTMS treatment [58], and there were no other side effects in the infants. One study that checked the child of a mother treated with rTMS reported that the exposure during pregnancy did not affect the cognitive or motor development of the child [77]. High frequencies above 40 Hz affect the lungs and immune system of the fetus [78, 79], and the maximum electromagnetic field applicable to the fetus is 800 mv/m [80]. However, the frequency used in rTMS treatment is generally 1 \u0026ndash; 25 Hz, and the scale of the electromagnetic field is 100 mv/m [81]. Nevertheless, additional research should be conducted because there are many aspects not yet researched.\u003c/p\u003e\n\u003cp\u003eMothers do not prefer the current treatment for peripartum depression. They are not willing to take antidepressants because they are concerned not only about the side effects that they will suffer but also the side effects to the fetus [82, 83] Besides, 2.5% of mothers suffer from treatment-resistant depression and have to choose a different treatment method [84]. In one survey on depression treatments, only 1.2% of the population accepted ECT treatment [85]. Although the acceptance rate of rTMS was also low, when knowledge about the treatment was shared, the acceptance rate increased by more than 50%, showing the possibility as a treatment method for PPD [86].\u003c/p\u003e\n\u003cp\u003eFrom the side of economic efficiency, rTMS may be a good alternative for treating PPD. For example, rTMS might save $112 per quality-adjusted life years (QALY) compared to antidepressants [87] and might save $8515 per year compared to ECTs [88]. This could reduce anxiety about the cost, which was one of the risk factors that had the greatest impact on pregnant women [89], and consequently, the socioeconomic costs of peripartum depression might be reduced.\u003c/p\u003e\n\u003cp\u003eLimitation and future study direction\u003c/p\u003e\n\u003cp\u003eRegarding the limitations of the meta-analysis, our results showed high heterogeneity, and the reason may be heterogeneity due to methodological diversity because the parameters of rTMS varied from study to study, or heterogeneity due to coincidence because the analysis was conducted with small sample-sized studies. However, because the parameters vary according to the patient's situation (e.g., the stimulation site changes according to symptoms and the frequency changes according to the stimulation site), it should be judged as clinical heterogeneity. Our results might also be constrained by the lack of patients and studies. Thus, the effects of rTMS on PPD and should be interpreted with caution. Future research should focus on the effects in the prenatal and infancy periods and establish parameters for rTMS, such as the site stimulation or frequency.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eWe collected data from existing documents and identified 11 studies that were suitable for a systematic review, of which five are suitable for meta-analysis. According to the analysis of the included studies, the therapeutic effect size of rTMS for PPD showed an SMD of 1.394 (95% CI: 0.920 \u0026ndash; 1.843), and the sensitivity analysis showed an SMD = 1.074 (95% CI: 0.777 \u0026ndash; 1.233), which is a significant effect, but this effect size could be overestimated because more than 50% of the studies were NRS, and some studies were at risk of bias Nonetheless, rTMS seems to have potential as a treatment for peripartum depression. The side effects of rTMS for PPD had an SMD of 0.346, (95% CI: 0.214 \u0026ndash; 0.506), which is meaningful. However, there were no serious side effects to the mothers or fetuses. From a variety of perspectives, the treatment of PPD using rTMS could be considered an alternative treatment to avoid exposure of the fetus to drugs and the severe side effects of ECT. Further research is required to increase the confidence in these results.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003ePPD\u003c/strong\u003e: Peripartum depression\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMDD\u003c/strong\u003e: Major depressive disorder\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eECT\u003c/strong\u003e: Electroconvulsive therapy\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMAO\u003c/strong\u003e: Monoamine oxidase\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003erTMS\u003c/strong\u003e: Repeated transcranial magnetic stimulation\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDLPFC\u003c/strong\u003e: Dorsolateral prefrontal cortex\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRCT\u003c/strong\u003e: Randomized controlled trial\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNRS\u003c/strong\u003e: Non-randomized studies\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDSM-5\u003c/strong\u003e: Diagnostic and Statistical Manual of Mental Disorders-5\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHDRS\u003c/strong\u003e: Hamilton Depression Rating Scale\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eROB2\u003c/strong\u003e: Risk of bias 2\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eROBINS-I\u003c/strong\u003e: The Risk of Bias Assessment tool for Nonrandomized Studies\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSMD\u003c/strong\u003e: Standardized Mean Deviation\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCI:\u003c/strong\u003e confidence interval\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMARDS\u003c/strong\u003e: Montgomery-\u0026Aring;sberg Depression Rating Scale\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBDI:\u003c/strong\u003e Beck Depression Inventory.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEPDS\u003c/strong\u003e: Edinburgh Postnatal Depression Scale\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQALY\u003c/strong\u003e: Quality adjusted life year\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCGI-S\u003c/strong\u003e: Clinical Global impression scale\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGAS\u003c/strong\u003e: Global Assessment Scale\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSF-36-V\u003c/strong\u003e: 36-item Quality of Life Health Survey Vitality scores\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSF-36-MH\u003c/strong\u003e: 36-item Quality of Life Health Survey Mental Health scores\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank the Korea Health Industry Development Institute(KHIDI) for supporting the training program for advanced medical device industry professionals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo data or materials were generated for this narrative review.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAffiliations\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDepartment of Medical Devices Industry, Dongguk University-Seoul (04620) 30, Pildong-ro 1 \u0026ndash;gil, Jung-gu, Seoul, Republic of Korea \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Hyune June Lee, Sung Min Kim, Ji Yean Kwon\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Authors contributions\u003c/p\u003e\n\u003cp\u003eHJ: Conceive the project, search strategy, screening literature, data extraction, bias evaluation, data analysis, and drafting the manuscript and revising. SM: supervised the entire procedures and helped to draft the manuscript. JY: Study design, screening literature, bias evaluation, data analysis, drafting the manuscript, and revising the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eCorresponding author\u003c/p\u003e\n\u003cp\u003eCorrespondence to Ji Yean Kwon([email protected])\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;No funding was obtained for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interest\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary information\u003c/strong\u003e\u003c/p\u003e\n\u003col\u003e\n\u003cli\u003eAppendix 1 searching strategy.docx\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e: How to searching using terms or mesh\u003c/p\u003e\n\u003cp\u003e2.Appendix 2 excluded studies.docx\u003c/p\u003e\n\u003cp\u003e: Excluded literature and the reason\u003c/p\u003e\n\u003cp\u003e3.Appendix 3 risk of bias assessment.docx\u003c/p\u003e\n\u003cp\u003e: Risk assessment of selected literature\u003c/p\u003e\n\u003cp\u003e4.Appendix 4 PRISMA checklist.docx\u003c/p\u003e\n\u003cp\u003e: PRISMA checklist\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAssociation D-AP: \u003cstrong\u003eDiagnostic and statistical manual of mental disorders\u003c/strong\u003e. 2013.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eWorld Health Organization maternal and child mental health\u0026nbsp;\u003c/strong\u003e[https://www.who.int/mental_health/maternal-child/maternal_mental_health/en/] Accessed on 31/09/20\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"3\"\u003e\n\u003cli\u003eBauer A, Knapp M, 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The typical treatment options include antidepressants and electroconvulsive therapy. However, these treatments do not ensure the safety of the fetus. Recently, repetitive transcranial magnetic stimulation has emerged as a promising treatment for neuropathies as well as depression. Nevertheless, many studies excluded pregnant women. This systematic review was conducted to confirm whether repetitive transcranial magnetic stimulation was a suitable treatment option for peripartum depression. \u003c/p\u003e\u003cp\u003eMethods\u003c/p\u003e\u003cp\u003eWe performed a systematic review followed the PRISMA guidelines. We searched studies in the MEDLINE, PsycINFO, EMBASE, and Cochrane library databases published until the end of September 2020. Eleven studies were selected for the systematic review, and five studies were selected for quantitative synthesis. Data analysis was conducted using Comprehensive Meta-Analysis 3 software. The effect size was analyzed using the standardized mean difference and the 95% confidence interval (CI) was determined by the generic inverse variance estimation method.\u003c/p\u003e\u003cp\u003eResults\u003c/p\u003e\u003cp\u003eThe therapeutic effect size of repetitive transcranial magnetic stimulation for peripartum depression was 1.394 (95% CI: 0.920 – 1.843), and the sensitivity analysis effect size was 1.074 (95% CI: 0.777 – 1.233), indicating a significant effect. The side effect size of repetitive transcranial magnetic stimulation for peripartum depression was 0.346, (95% CI: 0.214 – 0.506), which was a meaningful result. There were no serious side effects to the mothers or fetuses.\u003c/p\u003e\u003cp\u003eConclusions\u003c/p\u003e\u003cp\u003eFrom a variety of perspectives, repetitive transcranial magnetic stimulation can be considered an alternative treatment to treat peripartum depression to avoid the exposure of fetuses to drugs and the severe side effects of electroconvulsive therapy. Further research is required to increase confidence in the results.\u003c/p\u003e","manuscriptTitle":"Repetitive Transcranial Magnetic Stimulation Treatment for Peripartum Depression: Systematic Review \u0026amp; Meta-Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-11-19 16:19:53","doi":"10.21203/rs.3.rs-108764/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2020-12-31T00:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-12-30T00:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nthis is a very original and interesting article and I congratulate the authors. the methodology and form of the article are very clear and fluent. I believe that minor revisions are necessary to make the work more understandable:\n- a revision of English by a native speaker is necessary (there are some errors in punctuation and verbal construction);\n- why did you include the work of Tarhan et al., 2012 [69], if you say that in the meta-analysis it was not considered because detailed results are missing? wouldn't it be better to exclude it among the \"no outcome\" exclusion criteria?;\n- in table 3: among the listed adverse effects it would be more interesting to know which percentage of patients had adverse effects in addition to the absolute number;\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please publish my name with my report.**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"editorInvitedReview","content":"","date":"2020-12-18T00:00:00+00:00","index":1,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nThis study performed a systematic review to determine the efficacy of repetitive transcranial magnetic stimulation for peripartum depression. The authors successfully showed that repetitive transcranial magnetic stimulation can be considered an alternative treatment to treat peripartum depression to avoid the exposure of fetuses to drugs and the severe side effects of electroconvulsive therapy. This study has been well investigated. The reviewer has some suggestions to improve the manuscript. The reviewer comments are listed below.\n\nAbstract\nPlease confirm that the values listed here are correct: 95% CI, 0.920-1.843 and 95% CI, 0.777-1.233.\n\nIntroduction\nPage 4, paragraph 1\nPlease add more exact values for each complication.\n\nPage 4, paragraph 2\n\"pregnant women taking antidepressants\"\nPlease clarify the type of antidepressants. How about SSRI?\n\nPage 5 paragraph 1\nPlease cite the previous report on PRISMA guidelines.\n\nMethods\nI suggest clarifying the keywords which the authors used in each search engine.\nIn a previous study (Arch Womens Ment Health. 2020 Aug;23(4):469-478.), 17 studies were included.\n\nPage 6, paragraph 2\nThe authors may add the initials of authors who independently reviewed the literature.\n\nFigure 1.\nThe authors may delete Figure 1 and describe the extraction items in the Materials and Methods.\n\nTable 1\nWhat does * indicate?\n\nPage 22 paragraph 1\nThe rate of preterm birth was relatively high. In general, it has been reported to be around 5-8%.\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **No**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **No**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"reviewerAgreed","content":"","date":"2020-11-30T00:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-11-29T00:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-11-19T00:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-11-09T00:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-11-08T23:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-11-08T23:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2020-11-04T00:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"502e0e5c-3047-4971-a11d-dcf0f0fe45e6","owner":[],"postedDate":"November 19th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":1137783,"name":"Maternal \u0026 Fetal Medicine"}],"tags":[],"updatedAt":"2021-02-14T15:00:45+00:00","versionOfRecord":{"articleIdentity":"rs-108764","link":"https://doi.org/10.1186/s12884-021-03600-3","journal":{"identity":"bmc-pregnancy-and-childbirth","isVorOnly":false,"title":"BMC Pregnancy and Childbirth"},"publishedOn":"2021-02-09 15:00:30","publishedOnDateReadable":"February 9th, 2021"},"versionCreatedAt":"2020-11-19 16:19:53","video":"","vorDoi":"10.1186/s12884-021-03600-3","vorDoiUrl":"https://doi.org/10.1186/s12884-021-03600-3","workflowStages":[]},"version":"v1","identity":"rs-108764","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-108764","identity":"rs-108764","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}