Maternal Mental Health and TMS-Part One: Transcranial Magnetic Stimulation in the Treatment Of Postpartum Depression (PPD)

Tue, 02/22/2022 - 17:24

By Debra J. Stultz M.D.

     May 4, 2022, is World Maternal Mental Health Day. Organizations worldwide are attempting to increase awareness of mental health issues associated with pregnancy by growing the social media presence and various international activities. To join this movement, we will be starting a series on Transcranial Magnetic Stimulation (TMS) in maternal mental health, including treatment during pregnancy, postpartum depression, and postpartum OCD. The first in the series will focus on postpartum depression.

          Symptoms of postpartum depression present when Mothers feel they “should” be happy and can occur around the time of delivery and may persist long afterward. These patients are often overwhelmed with emotions, increased responsibility, sleep deprivation, fear, and physical recovery from the physical effects of pregnancy and delivery. Increased mood swings may be related to depression alone or a bipolar type illness. It may be challenging to distinguish postpartum depression and postpartum bipolar depression, especially when mixed features are present.   Symptoms may include insomnia, anxiety, irritability, loneliness, poor attachment with the infant, a strained relationship with others, obsessive ideation, intrusive thoughts, suicidal ideation, excessive guilt, feeling overwhelmed, decreased sex drive, fatigue, concentration/memory problems, and anhedonia may also be present. These symptoms can especially be of issue for Mothers separated from their child due to COVID infections. 

     Wang et al. 20211 completed a meta-analysis of 565 studies from 80 different countries or regions involving 1,236,365 women and found a prevalence of postpartum depression in 17.22% of the world’s population. Their study indicated PPD was linked to income and geographic development. In their review, 66 of the studies were from the United States, involving 242,105 patients and demonstrated a prevalence of 18.56%. Of the countries with at least five relevant studies, South Africa had the highest and Spain the lowest prevalence. Increased prevalence was found in single/divorced/widowed, less than 12 years education, lack of support from friends/family/parents, lack of support from their partner, pre-/post- term deliveries, those who were not breastfeeding, in situations with infant death, unplanned pregnancy, unsatisfied relationships with partners, smokers, alcohol use, and unsatisfied living situations. Minimal differences were found with two or more children, unemployment, the sex of the infant, maternal age, religion, mode of delivery, ethnicity, location of delivery (home vs. health facility), or gender preference. 

     Van der Zee-van den Berg et al. 20212 studied data from 1406 mothers using the Edinburgh Postnatal Depression Scale3 (EPDS) and 6-item State-Trait Anxiety Inventory4 (STAI-6) and found an increased risk of postpartum depression was associated with a prior history of depression, low maternal self-efficacy, a foreign language being spoken at home, and poor current health of the mother. An increased risk of anxiety was found with preterm birth, a history of depression, higher educational level, negative experience at delivery or during the first week postpartum, excessive infant crying, low maternal self-efficacy, poor maternal health, and low partner support. 

     Bauman et al. 20205 reviewed data from the CDC 2018 collection of information in the Pregnancy Risk Assessment Monitoring System (PRAMS) at 31 different sites and reported 13% of surveyed women reported postpartum depression. One in eight stated they were not even asked about depression during their postpartum visit. In their review, the prevalence of postpartum depression exceeded 20% in those less than or equal to 19 years of age, those who were American Indian/Alaska Native, smoked during or after pregnancy, experienced domestic violence before or during pregnancy, had depression before or during pregnancy, and in those whose infant had died since birth. 

     Slomian et al. 20196 studied the consequences of maternal postpartum depression with respect to the maternal consequences, the infant consequences, and the mother-child interactions, including bonding, breastfeeding, and the maternal role. Their report was a systematic review of 61 studies on maternal consequences, 73 on infantile consequences, and 19 on both the infant and maternal consequences of PPD. The studies on maternal consequences of PPD reported limitations due to physical health; increased bodily pain and poor health perceptions; lower mood scores one year after childbirth; lower self-esteem; higher levels of anger; lower scores for anger control; lower levels of positive affect; elevated levels of state and trait anxiety; and increased depression at one year postpartum if depression was found in the first weeks after childbirth. Additionally, more significant perceived stress; more financial problems; lower levels of household functioning; a 1.5 times increased risk of homelessness; more relationship difficulties; lower levels of perceived social support; increased romantic break-ups; increased sexual dysfunction; increased smoking; and increased levels of suicidal ideation were also reported. 

     Infant consequences of PPD were sometimes mixed but included the possibility of poor weight gain, more overall physical health problems for the child, increased diarrheal episodes, more significant pain, and increased pain response to vaccinations. Decreased cognitive development; delayed language development; effects on emotional development; higher fear scores and anxiety; lower social engagement; negative infant behaviors; increased behavioral problems at two years of age; more difficult temperament; less mature regulatory behaviors; and hyperactivity with inattention and physical aggression in the form of opposition. Also, increased febrile disease, increased risk of infant mortality, increased infant night-time awakenings and sleep disturbances, impaired motor development at 6-8 months, and decreased fine-motor scores at 18 months were reported. 

     Mother-child concerns reported were those of the mothers having lower perceived competence; more interruptions and breaks in parental care; children with increased television exposure; mothers spending less time playing with, reading to, and talking to children; and negative effects on bonding. Less success with breastfeeding; less-healthy practices when it comes to car seats, sleeping position, or having a smoke alarms in the house; increased health care and ER visits for the child; increased injuries for the child; decreased rate of immunizations and well-child visits; and increased perceptions that the child is fussy or demanding were also reported. 

     While antidepressant therapy is frequently used to treat postpartum depression, they can take time to be effective and are not without concerns and side effects during pregnancy and while breastfeeding. Many patients are unwilling to take antidepressants due to fears of weight gain or sexual dysfunction. Of course, psychotherapy should also be a part of the treatment plan and may be easier for the Mothers to attend with the current telehealth options. ECT7 has been used in more extreme cases but has the risk of anesthesia, hospital cost, cognitive concerns, and other potential side effects to be considered. Zaulresso (brexanolone)8 has been FDA approved for postpartum depression for those 18-45 years of age and is an IV treatment given over 60 hours at a health care facility. This option is not only a significant burden of time and separation from the infant, but the costs of this treatment must also be considered. Transcranial Magnetic Stimulation (TMS) may be a very reasonable treatment alternative for those with postpartum depression.

     One of the first reports of rTMS in postpartum depression reported was Ogden et al. 19999 in a 40-year-old female with a previous episode of postpartum depression with psychotic features, which developed depression again after her 2nd child. She presented after attempting infanticide. She received 20 Hz TMS at 100% MT of 1200 pulses to the left prefrontal cortex for 13 treatments along with citalopram and risperidone. She had documented improvement on her Hamilton Depression Rating Scale-1710, the Beck Depression Inventory11, and a Visual Analogue Scale12. The study revealed her HDRS-17 improved from 29 to 3. Her Beck Depression Inventory improved from 48 to 13. And, the Visual Analogue Scale from 8.2 to 3.4. 

          Tan et al. 200810 reported on a 30-year-old patient with five prior episodes of major depression that found out she was pregnant while receiving TMS. She was given left dorsolateral prefrontal cortex TMS at 25 Hz, 110% MT, and 1000 pulses per treatment of 2 seconds on and 28 seconds off for 35 sessions in her 1st trimester, 15 sessions in the second trimester, and eight sessions in her third trimester.   When the baby was 20 days old, rTMS was restarted, and 19 more sessions were given in the next 7.5 months after the delivery. She had a total of 77 treatments. Based on the HAM-D-17 scale, she responded at the 50th session and reached remission after the 68th session. Her depression was still in remission 22 months after the delivery. No seizures or serious side effects were reported.

     Garcia et al. 200913 studied nine antidepressant-free females (except for one patient taking a total of seven 2-mg diazepam’s throughout the treatment for Meniere-related vertigo) using 20 rTMS treatments of 10 Hz and 120% MT to the left dorsolateral prefrontal cortex for 4 seconds of stimulation and 26 seconds off for a total of 3000 pulses. While studying the Hamilton Rating Scale for Depression-24, Edinburgh Postnatal Depression Scale14, Inventory of Depressive Symptomatology-Self-Report15 and Clinical Global Impressions-Severity16 scores at the end of treatment, 30 days post-treatment, three months post-treatment, and six months post-treatment. Their study demonstrated signs of improvement by the end of week 2.  Eight patients achieved remission, and of those, six remained in remission (one was lost to follow-up). They also reported improvement in maternal bonding using the Postpartum Bonding Questionnaire17

     Myczkowski et al. 201218 completed a randomized, placebo-controlled, double-blind pilot study with TMS in fourteen patients with a mean age of 28.15 years using sham or active 5 Hz left-sided dorsolateral prefrontal cortex stimulation at 120% MT of 25 trains lasting 10 seconds with 20-second intervals and  1250 pulses for 20 sessions. Three patients used clonazepam 1 mg/day for insomnia and/or physical symptoms. All of the 14 patients breastfed their babies until at least week 6. While using the Hamilton Depression Rating Scale-17, EPDS, Global Assessment Scale19, Clinical Global Impression Scale16, and the Medical Outcomes Study 36-item short-form health survey20 they also included a neurocognitive battery in their study of the Trail Making Test21, Wisconsin Card Sorting Test22, Controlled Oral Word Association Test23, Victoria Stroop Test24, Rey Auditory Verbal Learning Test25, and the WAIS-III26. They suggested that rTMS improved postpartum depression with marginal social and cognitive functioning gains. Although the overall Social Adjustment Scale Self-Report27 findings in the TMS treated population were not statistically significant, improvement was noted at weeks 4 and 6 on the “Work at Home” subscale.

     Ozmut et al. 201528 treated 15 patients with TMS during pregnancy and the postpartum period, eight of which had significant depression in the postpartum period. Their study used rTMS at 80% MT, 20 Hz, with a duration of 2 seconds delivered 20 times with 50-second intervals for 1000 pulses. Using the Hamilton Depression Rating Scale-17, Hamilton Anxiety Rating Scale-1429, and the Edinburgh Postnatal Depression Scale, they suggested maintenance rTMS may be effective in pregnant patients continuing treatment into the postpartum period. Four of their patients had decreased Hamilton Depression scores, eight had improvement on the Edinburgh Depression Scale, and six improved their Hamilton Anxiety scores. Other than mild headaches, no serious side effects were reported to the patients or the infants. 

     Brock et al. 201630 studied 19 medication-free outpatients with unipolar non-psychotic postpartum depression following the Edinburgh Postnatal Depression Scale. They reported the EPDS score decreased from a mean of 20.6 to 8.2, with fourteen patients achieving remission. They used 10 Hz rTMS at 120%MT for 4-second trains 26 ITI and 3000 pulses to the left prefrontal cortex for up to eight weeks with a three-week taper. The authors reported decreased EPDS scores of less than ten was demonstrated in 73.7% of patients.   No serious side effects were reported with this treatment.

     Most recently, Cox et al. 202031 treated six patients with postpartum depression using 20 sessions left dorsolateral prefrontal cortex of 10 Hz frequency,  120% MT, for four seconds of stimulation and 26 seconds rest for 3000 pulses while following the Beck Depression Inventory, the Edinburgh Postnatal Depression Scale and State-Trait Anxiety Inventory4 scores, all of which declined over the four weeks of treatment. Four of the six achieved remission, and two responded based on the EPDS. Using BDI scores, only one achieved remission. There was no disruption in lactation with TMS treatment. Cognitive performance was also monitored using the MMSE32, Trails B33, and Word List Generation34. There was no evidence of cognitive changes. Mean BDI and EPDS scores at 3 and 6 months follow-up remained below levels of treatment initiation.  

     Transcranial Magnetic Stimulation has also been used to treat bipolar disorder in the postpartum period, as reported by Cohen et al. 200835. The authors described a 36-year old female with a history of bipolar disorder who developed depression around month five during her pregnancy. She was given 1 Hz rTMS at 100% MT and 1600 pulses to the right dorsolateral prefrontal cortex. She remained stable throughout the rest of her pregnancy. Later she presented with manic/hypomanic symptoms on the 20th day postpartum. She was given one session of 20 Hz rTMS to the right dorsolateral prefrontal cortex at 100% MT with 1600 pulses, improving her mania, but her depression returned. Because of the rapid cycling nature of her illness, she was eventually switched to bilateral 20 Hz rTMS of 800 pulses each side at 100% MT weekly x 5, then twice a month x2, and once a month x2 for a total of 10 sessions. Six months later, she started Lithium and stopped breastfeeding. She was treated with TMS while avoiding medications during her pregnancy and six months postpartum, allowing her to breastfeed her child. 

TMS provides a reasonable alternative to traditional therapies. TMS has been approved for use in depression, OCD, smoking, and depression associated with anxiety and may be of great clinical benefit in the postpartum period. More information on postpartum depression may be found through the Postpartum Support International group at 1-800-944-4773, #maternalMHmatters on social media, PSI’s Facebook page, and wmmhday.postpartum.net. The Postpartum Support International group is active in the United States and 42 different countries, training professionals and providing direct peer support to patients and their families.

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