Accelerated TMS for Perinatal Depression (PAiNT)

Perinatal Accelerated iTBS Neuromodulation Therapy

We are studying a treatment for depression called accelerated Transcranial Magnetic Stimulation (TMS) among pregnant and postpartum individuals. TMS is a focal, non-invasive form of brain stimulation that is cleared by the Food and Drug Administration for depression. Typically, traditional TMS involves daily treatments for 6-8 weeks. In this study, we will offer an accelerated form of TMS that involves multiple daily treatments for 5 days.

Study Overview

• Status: Recruiting
• Conditions: Post Partum Depression; Major Depressive Disorder; Perinatal Depression
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation

Detailed Description

Perinatal depression is underdiagnosed, undertreated, and understudied. Approximately one in five individuals will experience perinatal depression, which spans from conception to one year after birth. Untreated perinatal depression increases the risk of stillbirth, preterm birth, substance abuse, parental suicide, and developmental delay. There are limited empirical data to guide treatment of perinatal depression. Psychotherapy can be effective for mild-to-moderate depression, but it is slow acting and difficult to access. Antidepressants show inconsistent benefits and safety; moreover, patients report feeling anxious or guilty about taking them.

Transcranial magnetic stimulation (TMS) is FDA cleared treatment for major depressive disorder, adolescent depression, late life depression, and anxious depression. It has also shown promise as a safe and effective biological intervention for perinatal depression for both the mother and fetus. One of the most exciting new developments in neurostimulation is accelerated intermittent theta burst stimulation (iTBS), a TMS protocol that involves multiple daily treatments rather than once daily treatment. A specific accelerated TMS protocol called Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) was FDA cleared in September 2022 because of its rapid and robust antidepressant effects. In an open-label study (n=21), SNT significantly reduced depression in one day and yielded 90.5% remission after five days. Importantly, there is no evidence that accelerated TMS protocols pose more risk than conventional TMS protocols that have a strong safety profile.

While SNT is a potential breakthrough treatment, it has not been tested in peripartum individuals. Accelerated iTBS may expedite depressive symptom improvement and reduce the need for pharmacotherapy for individuals struggling with perinatal depression. If tolerable and efficacious, this treatment modality may increase the viable treatment options available to peripartum women with depressive symptoms.

In this pilot trial, patients who are currently pregnant or postpartum with treatment-resistant depression (n=12) will receive a modified SNT with neuronavigation. Treatment site location will be guided by MRI when possible given the promising internal findings highlighted above. However, if neuroimaging is not chosen by the patient, unsafe for the patient for any reason, or not tolerable for the patient, we will offer treatment with scalp-based measurement (i.e., TMS targeting based on Beam F3 method). Overall, this study is critically important for informing the viability of future accelerated iTBS trials in a peripartum population and may shape the future of affective treatment options in this patient group.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Interventional Psychiatry Research Group; Phone Number: 617 525 3536; Email: mgbpaint@mgb.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Interventional Psychiatry Research Group; Phone Number: 617 525 3536; Email: mgbpaint@mgb.org
      • Principal Investigator: Joseph J Taylor, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-55
• All individuals must be 14-34 weeks gestational age or within one year of delivery at the time of treatment. The odds of delivery nears 10% after 36 weeks, which would limit participants from being able to complete the study and interfere with the primary study aim to understand safety and tolerability. Additionally, after 36 weeks, the standard of care is weekly obstetric check-in visits, which would be challenging for patients to complete given the time demands of the study protocol.
• Patients will not be scanned after 32 weeks gestational age due to the time needed to construct the individualized treatment target. Individuals seeking treatment beyond 32 weeks will be offered scalp-based target localization so as not to limit patient access to care.
• English proficiency sufficient for informed consent, questionnaires/tasks, and treatment
• Primary diagnosis of major depressive disorder per DSM-V criteria (MINI International Neuropsychiatric Interview/ Structured Clinical Interview for DSM-5): >20 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and moderate to severe level of treatment resistance (Maudsley Staging Method)
• Stable antidepressant medication regimen, or remain medication free, for 4 weeks prior to treatment and to remain on this regimen throughout the treatment course. We request that this regimen remain stable until the 1 month post-treatment if clinically appropriate.
• Primary clinician (e.g. psychiatrist, therapist, psychologist, APRN, PA, etc.) responsible for psychiatric care before, during, and after the trial in addition to an obstetric provider responsible for obstetric care.
• Agreement to lifestyle considerations: Continue usual intake patterns of caffeine- or xanthine-containing products (e.g. coffee, tea, soft drinks, chocolate) throughout treatment

Exclusion Criteria:

• Concurrent use of rapid acting antidepressant agent (ketamine/esketamine/ECT)
• Receiving or planning to receive other TMS treatments during course of participation
• Obstetric concerns: Preeclampsia and/or current frequent, painful contractions (more than one every 10 minutes)
• History of: Neurosurgical intervention for depression, autism spectrum disorder, intellectual disability, severe cognitive impairment, significant neurological illness (e.g., dementia, Parkinson's, Huntington's, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, brain lesion), untreated or insufficiently treated endocrine disorder, and/or treatment with investigational drug or intervention during the study period
• ≥ 30% change in MADRS score between screening and baseline
• Anyone presenting with: Mania or hypomania, psychosis, active suicidal ideation with plan and some intent to act or a suicide attempt (defined by C-SSRS) within the past 3 months, neurological lesion, contraindications to either TMS or MRI (e.g., metallic implants, severe insomnia > 4 hours per night with hypnotic, etc.), and/or current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal
• Existing tinnitus (ringing in the ears) that causes functional impairment
• History of retinal detachment or other retinal pathology
• Severe borderline personality disorder
• Any other condition deemed by the PI to interfere with the study or increase risk to the participant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Open-label aiTBS for pregnant/postpartum individuals; 10 iTBS treatment sessions per day (18,000 pulses/day) for 5 consecutive days (90,000 pulses total) to the dorsolateral prefrontal cortex (DLPFC). In the unlikely event that a participant is late for an hourly treatment, then the treatment will be delayed accordingly. The minimum gap between treatments will be 25 minutes. Each iTBS treatment will consist of 60 cycles of 10 bursts of three pulses at 50 Hz delivered in 2-second trains (5 Hz) with an 8-second intertrain interval. Stimulation will be delivered at 90% resting motor threshold (rMT), adjusted for depth of the identified functional connectivity target or based on traditional scalp measurements.

Device: Transcranial Magnetic Stimulation; Non-invasive form of brain stimulation.; Other Names: TMS; aiTBS; Accelerated intermittent theta burst stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability as measured by ratings of the Client Satisfaction Questionnaire (CSQ-8)	The CSQ-8 asks individuals about their overall experience with aTMS.Higher scores indicate a greater level of tolerability. We hypothesize that participants will report high levels of treatment satisfaction (>24) on the Client Satisfaction Questionnaire (CSQ-8). The primary outcome will be a composite defined as meeting 3 out of 4 metrics listed here.	1 month after treatment
Acceptability as measured by percentage of individuals who complete an entire treatment course	Higher percentage of individuals who completed an entire course (i.e., 50 treatments) indicates higher acceptability. We hypothesize that 9/12 participants will complete at least 75% of treatments. The primary outcome will be a composite defined as meeting 3 out of 4 metrics here.	1 month after treatment
Safety as measured by reports of adverse events	We will monitor and report the rate of serious adverse events, including maternal seizures in the sample. We hypothesize that there will be no serious adverse events.	1 month after treatment
Feasibility as measured by the number of individuals treated throughout the study	Report of the number of individuals who received treatment throughout the entire study (i.e., approximately 2 years). We hypothesize that we will be able to enroll and treat 12 participants in two years. The primary outcome will be a composite defined as meeting 3 out of 4 metrics here.	From the beginning to the end of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the effects of accelerated TMS on birth outcomes and lactation	We will monitor and report neonatal APGAR scores from infants delivered from mothers in the sample, birth weights, intradelivery maternal pain scores, birth modality (e.g. vaginal or C-section), and maternal blood loss. For individuals postpartum, we will ask participants to log their milk supply daily during treatment to determine any effects	Throughout the 5 days of treatment to 1 month post treatment
Montgomery-Åsberg Depression Rating Scale (MADRS)	A clinician rated tool used to assess the severity of depression in adults. The MADRS consists of 10 items, each scored on a 7 point scale 0-6 with higher scores indicating more severe depressive symptoms.	From baseline to 1 month post treatment.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beck Depression Inventory (BDI)	Depression severity rating scales (0-63, higher numbers indicate higher severity)	Before treatment, daily throughout treatment, 2 week post treatment, and 1 month post treatment
Beck Anxiety Inventory (BAI)	Anxiety severity rating scale (0-63, higher numbers indicate higher severity)	Before treatment, daily throughout treatment, 2 week post treatment, and 1 month post treatment
Young Mania Rating Scale (YMRS)	11 item scale evaluating mania. Scored 0-60. Higher score indicates worse outcome/higher mania	Before treatment, daily throughout treatment, 2 week post treatment, and 1 month post treatment
Edinburgh Postnatal Depression Scale	A scale created to help identify women who may be suffering from postpartum depression. Each question is scored 0-3, with a maximum score of 30. A score of more than 10 suggests minor or major depression may be present.	Before treatment, 2 weeks after treatment, and 1 month after treatment.
Hamilton Rating Scale for Depression	Designed to rate the severity of depression in individuals. Scores range from 0-52, a higher score indicating more severe depression.	Before treatment, 2 weeks after treatment, and 1 month after treatment.
Maternal Ante/Postnatal Attachment Scale	Developed to assess a new mother's emotional response to her infant. Each item is rated on a 5-point scale (typically ranging from 1 to 5). Lower scores indicate lower attachment.	Before treatment, 2 weeks after treatment, and 1 month after treatment.
PTSD Checklist with Criterion A for DSM-5	20 item PTSD scale, scored 0-80. Higher scores indicate worse symptoms.	Before treatment, 2 weeks after treatment, and 1 month after treatment.
Adult Temperament Questionnaire	77-item self-report questionnaire assessing individuals temperament and personality. Scores range from 0-539, with scores in subsections of the questionnaire indicating various affects and temperaments.	Before treatment, 2 weeks after treatment, and 1 month after treatment.
Perinatal Anxiety Screening Scale	31-item self-report instrument designed to screen for problematic anxiety in antenatal and postpartum women. Each item is rated on a 4-point Likert scale (0-4), with higher scores indicating greater anxiety.	Before treatment, 2 weeks after treatment, and 1 month after treatment.
Emotion Reactivity Scale	21-item self-report measure designed to assess an individual's emotional reactivity. Responses are scored on a 5-point Likert scale, with higher scores indicating greater emotional reactivity.	Before treatment, 2 weeks after treatment, and 1 month after treatment.
Standford Expectations of Treatment Scale	Measures patient outcome expectancy in clinical trials, specifically focusing on positive and negative treatment expectations. Scores range from 3-21, with higher scores indicating higher belief treatment will work, lower scores indicating more skepticism/anxiety about treatment being successful.	Baseline visit
Patient Global Impressions	A single question assessing a patient's perception of their health or condition. Scores range from 1-7, one being the participant believes they are not at all ill, seven being an extremely ill individual.	Baseline, 2 weeks after treatment, 1 month after treatment
World Health Organization Quality of Life - Brief Version	26-item questionnaire to assess quality of life. Uses a 5-point Likert scale, with higher scores indicating higher perceived quality of life.	Before treatment, 2 weeks after treatment, and 1 month after treatment.

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2025
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: May 2, 2025
• First Submitted That Met QC Criteria: May 5, 2025
• First Posted (Actual): May 13, 2025

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Postpartum Depression; Postpartum; Major Depressive Disorder; TMS; Perinatal Depression; Perinatal; Pregnant; Accelerated TMS
• Additional Relevant MeSH Terms: Urogenital Diseases; Mental Disorders; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Mood Disorders; Puerperal Disorders; Depressive Disorder; Depressive Disorder, Major; Depression, Postpartum; Therapeutics; Magnetic Field Therapy; Transcranial Magnetic Stimulation
• Other Study ID Numbers: 2025P001058; Women's Brain Initiative (Other Grant/Funding Number: Brigham and Women's Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No