Transcranial Magnetic Therapy (TMS) for Treatment of Perinatal Depression

This is a prospective, open-label, single-arm clinical study designed to evaluate the feasibility, acceptability, safety, and preliminary clinical outcomes of transcranial magnetic stimulation (TMS) for the treatment of perinatal depression. The study will examine the use of TMS in women experiencing major depression during pregnancy or within the first year postpartum.

Depression during pregnancy and the postpartum period is associated with significant maternal health risks and adverse pregnancy and infant outcomes. Although effective treatments for depression are available, some women may prefer nonpharmacologic treatment options or may experience inadequate improvement with existing treatments. TMS is a noninvasive brain stimulation treatment cleared by the U.S. Food and Drug Administration (FDA) for major depressive disorder in adults. However, evidence regarding its use during pregnancy and the postpartum period remains limited. Additional research is needed to establish the feasibility, acceptability, safety, and potential clinical benefits of TMS in this population.

The primary objective is to determine whether a course of TMS treatment is feasible and acceptable for women with perinatal depression. Feasibility will be assessed through treatment retention and adherence, including the proportion of participants who complete at least 20 treatment sessions and the proportion who attend at least 80% of scheduled sessions. Acceptability will be evaluated using participant-reported treatment satisfaction. Safety will be assessed through systematic monitoring of adverse events, including maternal and fetal outcomes when applicable, and the completeness of clinical data will also be evaluated.

A secondary objective is to collect preliminary information about the clinical effects of TMS on depressive symptoms. Exploratory analyses will examine changes in depression severity, anxiety, rumination, sleep quality, trauma-related symptoms, daily functioning, and maternal attachment during treatment. The study will also evaluate rates of clinical response and remission and explore whether improvements in depressive symptoms are maintained approximately one month after treatment completion.

Participants will receive an individualized course of TMS using established clinical stimulation parameters targeting the left dorsolateral prefrontal cortex, a brain region involved in mood regulation. Treatment will continue for a minimum of 20 sessions, with additional sessions provided as needed based on clinical response, up to a maximum of 36 sessions. Participants who meet the study's remission criteria after completing at least 20 sessions may transition to follow-up.

Clinical assessments will be conducted before treatment, weekly during treatment, and approximately one month after the final treatment session. Standardized clinician-rated assessments and participant questionnaires will be used to evaluate changes in psychiatric symptoms, functioning, and treatment experience. Maternal safety will be monitored throughout treatment, with additional obstetric monitoring and coordination with prenatal care providers for pregnant participants.

For participants enrolled during pregnancy, maternal and infant medical records will be reviewed approximately six months after delivery. This review will examine maternal mental health, pregnancy and delivery complications, postpartum health, and infant outcomes, including birth characteristics, neonatal complications, and health status through six months of age.

Because this is a single-arm, open-label study without a comparison group, the findings will primarily provide information about the feasibility, acceptability, and safety of delivering TMS during the perinatal period, along with preliminary estimates of changes in depressive symptoms. The results will inform the design of future controlled clinical trials evaluating TMS as a treatment option for perinatal depression.

All participants will receive active transcranial magnetic stimulation (TMS) targeting the left dorsolateral prefrontal cortex (DLPFC) using the NeuroStar TMS system. Treatment will consist of standard repetitive TMS (10 Hz) or intermittent theta burst stimulation (iTBS), delivered at 120% of the individual's resting motor threshold. Participants will receive one treatment session per day, up to five days per week, for a total of 20-36 sessions over approximately 4-8 weeks. Participants who achieve remission after completing at least 20 sessions may end treatment, while those who have not achieved remission may continue treatment for up to 36 sessions. All participants will be monitored for safety and clinical response throughout treatment.

Device: Transcranial Magnetic Stimulation (TMS)

Participants will receive active transcranial magnetic stimulation (TMS) using the NeuroStar TMS system, targeting the left dorsolateral prefrontal cortex (DLPFC). Treatment will use FDA-cleared stimulation parameters for major depressive disorder, including standard repetitive TMS (rTMS) at 10 Hz (3,000 pulses per session) or intermittent theta burst stimulation (iTBS; 600 pulses per session). Stimulation intensity will be set at 80-120% of each participant's resting motor threshold. Participants will receive one session per day, up to five days per week, for a total of 20-36 sessions over 4-8 weeks.

Plazo: 8 weeks post baseline

Proportion of participants who complete at least 20 TMS treatment sessions.

Plazo: 8 weeks post baseline

Proportion of participants who complete at least 80% of their scheduled TMS treatment sessions.

Plazo: 8 weeks post baseline

Participant satisfaction with TMS treatment measured using the 8-item Client Satisfaction Questionnaire (CSQ-8). Total scores range from 8 to 32, with higher scores indicating greater satisfaction. A score of 24 or higher is the predefined acceptability threshold.

Plazo: Throughout treatment (up to 8 weeks), with maternal medical record review 6 months (+/- 15 days) after delivery for participants enrolled during pregnancy

Incidence, severity, and relatedness of adverse events (AEs) and serious adverse events (SAEs) associated with TMS treatment.

Plazo: Throughout treatment (up to 8 weeks post baseline) and up to delivery for participants enrolled during pregnancy

Incidence, severity, and relatedness of adverse events (AEs) and serious adverse events (SAEs) related to the fetus.

Plazo: birth through 6 months (+/- 15 days) postpartum

Incidence, severity, and relatedness of adverse events (AEs) and serious adverse events (SAEs) related to the infant from birth through 6 months postpartum for participants enrolled during pregnancy

Plazo: Baseline, after every 5 treatments (once/week for up to 8 weeks), and 1 month after treatment

Change in clinician-rated depressive symptoms measured using the Montgomery-Åsberg Depression Rating Scale (MADRS). Total scores range from 0 to 60, with higher scores indicating greater depression severity.

Plazo: Screening, baseline, after every 5 treatments (once/week for up to 8 weeks), and 1-month follow-up

Change in depressive symptoms measured using the 10-item Edinburgh Postnatal Depression Scale (EPDS). Scores range from 0 to 30, with higher scores indicating greater depressive symptom severity.

Plazo: Baseline, daily after each TMS treatment, and 1-month follow-up

Change in depressive symptoms measured using the Quick Inventory of Depressive Symptomatology (QIDS). Total scores for the 16-item version range from 0 to 27, with higher scores indicating more severe depression.

Plazo: Baseline, after every 5 treatments (once/week for up to 8 weeks), and 1-month follow-up

Change in anxiety severity measured using the 7-item Generalized Anxiety Disorder scale (GAD-7). Scores range from 0 to 21, with higher scores indicating more severe anxiety.

Plazo: Baseline, after every 5 treatments (once/week for up to 8 weeks), and 1-month follow-up

Change in repetitive negative thinking measured using the Ruminative Responses Scale (RRS). The 22-item scale assesses rumination related to depressive symptoms, self-reflection, and brooding. Higher scores indicate greater rumination.

Plazo: Baseline, after every 5 treatments (once/week for up to 8 weeks), and 1-month follow-up

Change in sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI). Global scores range from 0 to 21, with higher scores indicating poorer sleep quality.

Plazo: Baseline, after every 5 treatments (once/week for up to 8 weeks), and 1-month follow-up

Change in posttraumatic stress symptoms measured using the PTSD Checklist for DSM-5 (PCL-5). Scores range from 0 to 80, with higher scores indicating greater symptom severity.

Plazo: Baseline, end of treatment (up to week 8), and 1-month follow-up

Change in functional impairment measured using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Higher scores indicate greater disability or difficulty with daily functioning.

Plazo: Baseline, end of treatment (up to week 8), and 1-month follow-up

The MAAS and MPAS are 19-item self-report questionnaires assessing maternal emotional attachment to the fetus during pregnancy (MAAS) and to the infant following birth (MPAS). The MAAS evaluates the quality and intensity of maternal attachment, while the MPAS assesses attachment quality, pleasure in interaction, and absence of hostility. Both scales yield total scores ranging from 19 to 95, with higher scores indicating stronger, more positive maternal attachment. Lower scores suggest greater difficulties with maternal-fetal or maternal-infant bonding.

Plazo: After 20 TMS sessions (week 4), end of treatment (up to 8 weeks from baseline), and 1-month follow-up

Proportion of participants achieving at least a 50% reduction in depressive symptom severity relative to baseline, assessed using Montgomery-Åsberg Depression Rating Scale (MADRS).

Plazo: After 20 TMS sessions (week 4), end of treatment (up to 8 weeks from baseline), and 1-month follow-up

Proportion of participants meeting remission criteria, defined as MADRS score ≤10.

Plazo: End of treatment (up to 8 weeks from baseline) and 1-month follow-up

Maintenance of improvement in depressive symptoms, assessed by comparing depression severity at treatment completion with Montgomery-Åsberg Depression Rating Scale (MADRS) scores obtained one month after the final TMS session.

TRANSCRANIAL MAGNETIC THERAPY (TMS) FOR TREATMENT OF PERINATAL DEPRESSION