rTMS for Peripartum Depression

An Open Label Trial of Repetitive Transcranial Magnetic Stimulation (rTMS) for Peri-partum Depression.

Repetitive Transcranial Magnetic Stimulation (rTMS) is a neuromodulatory technique that is effective in major depression. There is preliminary evidence suggesting that rTMS is effective in peripartum depression as well, however this comes from a number of very small studies.

The objective is to study the effectiveness of rTMS in peripartum depression. The investigators will do so using an open label design in which participants will receive rTMS for four weeks. The focus is on clinical improvement in depressive symptoms; however the investigators will also look at other aspects such as perinatal anxiety and maternal-infant bonding as measured by self-report questionnaires.

Study Overview

• Status: Withdrawn
• Conditions: Postpartum Depression; Antepartum Depression; Peripartum Depression
• Intervention / Treatment: Device: Transcranial Magnetic Stimulator

Detailed Description

Peripartum Depression (PPD) is common and severely disabling. Pharmacological intervention remains the first line of treatment, however many patients do not experience any benefits from them. Furthermore, many women are hesitant about pharmaceutical interventions due to the unknown effects on foetal health and lactation. Hence novel treatment approaches are required for such patients. Neuromodulation techniques involve selective targeting of brain areas which are promising avenues for such depressed patients.

Transcranial magnetic stimulation (rTMS) is an investigational and therapeutic modality that impacts neurons by delivering patterned energy safely and noninvasively. In response to this patterned energy, neurons fire, and adapt by changing their connection strengths. This change in connection strength is believed to be the underlying mechanism whereby rTMS has therapeutic benefit in conditions such as Major Depressive Disorder (MDD). There are preliminary evidences suggesting that it is effective in PPD as well, however this comes from a number of very small studies and is therefore unclear.

Given the promising preliminary evidence, the investigators propose to study the effectiveness of intermittent Theta-Burst Stimulation rTMS (iTBS) to the left dorsolateral prefrontal cortex (DLPFC) in treating PPD. Participants with PPD will receive iTBS rTMS for four weeks (20 sessions) in an open label manner. The primary measure will be clinical improvement in depressive symptoms as measured by change in the Montgomery-Asberg Depression Rating Scale (MADRS) with iTBS-rTMS. In addition, the investigators will look at other aspects such as peripartum anxiety and maternal attachment during treatment and 8 weeks postpartum.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alexander McGirr, MD, PhD; Phone Number: 403-210-6410; Email: alexander.mcgirr@ucalgary.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 1N4
      • University of Calgary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women currently experiencing peripartum depression as determined by the MINI-International Neuropsychiatric Interview
• Depressive episode of at least moderate severity, as indicated by a score of ≥15 (ante-partum) or ≥12 (post-partum) on the Edinburgh Post-Natal Depression Scale (EPNDS).
• Are currently pregnant or 1 month post-delivery
• Refuse antidepressant therapy, or have depression that has not improved with psychotropics and/or psychotherapy
• Be willing to remain on a stable medication regimen for 2 weeks prior the study and during the study
• Aged 18-40 years

Exclusion Criteria:

• Epilepsy, history of seizures or pre-eclampsia
• Previous Stroke
• Current Alcohol Use Disorder
• History of psychosis
• Bipolar Disorder
• Current suicidal ideation
• Intracranial metallic objects (dental hardware is not an exclusionary criteria)
• Unstable medical condition
• have failed a course of ECT in the current episode. Previous ECT treatment outside of the current episode does not influence inclusion.
• history of non-response to rTMS treatment .
• have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of epilepsy, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than or equal to 5 minutes
• have concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump
• have any significant obstetrical complications
• If participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study
• have a clinically significant laboratory abnormality, in the opinion of study physician
• are currently (or in the last 4 weeks) taking lorazepam greater than 2 mg daily (or equivalent) due to the potential to limit rTMS efficacy
• are currently (or in the last 4 weeks) taking lorazepam greater than or equal to 2 mg daily

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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 iTBS rTMS; Participants will receive repetitive transcranial magnetic stimulation (rTMS) as a treatment for depression	Device: Transcranial Magnetic Stimulator; Repetitive Transcranial magnetic stimulation (rTMS) will be delivered using a MagPro X100 device with B70 coil and the intermittent theta burst (iTBS) protocol to the left dorsolateral prefrontal cortex. Participants will receive daily treatments (Monday-Friday) over four weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montgomery-Asberg Depression Rating Scale (MADRS) scores	Change from baseline in severity of depressive symptoms at 2 weeks and 4 weeks as measured by the MADRS, a clinician-rated instrument. The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes. The overall score ranges from 0 - 60. Cutoff points are 0-6 = normal, 7-9 = mild depression, 20-34 = moderate depression, >34 = severe depression.	Administered at baseline, at the halfway point (week 2), and after rTMS treatment (week 4).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Clinical Remission of Depressive Symptoms	Number of participants with a score of </= 10 on the MADRS	Administered at baseline, at the halfway point (week 2), and after rTMS treatment (week 4)
Rate of Clinical Response in Depressive Symptoms	Number of participants with a >/= 50% reduction in MADRS scores	Administered at baseline, at the halfway point (week 2), and after rTMS treatment (week 4)
Perinatal Anxiety Symptoms	Perinatal Anxiety symptoms will be assessed using the Perinatal Anxiety Screening Scale (PASS). The PASS measures self-reported feelings of anxiety in the peripartum period. PASS scores range from 0-93, interpretations are as follows: 0-20 = asymptomatic, 21-41 = mild-moderate symptoms, and 42-93 = severe symptoms.	Administered at baseline, at the halfway point (week 2), and after rTMS treatment (week 4)
Anxiety Symptoms	The State-Trait Anxiety Inventory (STAI) measures self reported feelings of extrinsic "state" anxiety and intrinsic "trait" anxiety. The STAI scores range from 20-80, with higher scores correlating to greater anxiety.	Administered at baseline, at the halfway point (week 2), and after rTMS treatment (week 4)
Antenatal Maternal Attachment	The Maternal Antenatal Attachment Scale (MAAS) assesses self-reported feelings of the mother-child relationship before birth. Scores range from 19-95 on the MAAS, with lower scores representing lower levels of attachment.	If the participant is antenatal, the MAAS will be administered at baseline and after rTMS treatment (week 4).
Postnatal Maternal Attachment	The Maternal Postnatal Attachment Scale (MPAS) assesses self-reported feelings of the mother-child relationship after birth. Scores range from16-80 on the MPAS, with lower scores representing lower levels of attachment.	If the participant is postnatal, the scale will be administered at baseline and after rTMS treatment (week 4). All participants will complete the MPAS at 8 weeks postpartum.
Quick Inventory of Depressive Symptomatology- Self-report (QIDS-SR)	The QIDS -SR is a self-reported measure of depressive symptoms. Total scores range from 0 to 27, with higher scores representing greater severity of depression. Score interpretations are as follows: 0-7 = normal, 8-12 = mild, 13-16 = moderate, 17-20 = moderate to severe, 21-27 = severe.	Administered at baseline, halfway (week 2) and after rTMS treatment (week 4). All participants will complete the QIDS-SR at 8 weeks postpartum.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Adverse events will be tracked and recorded	Daily Monday-Friday throughout study (4 weeks)
Side Effects	Side effects will be tracked through a comfort rating questionnaire. The comfort rating questionnaire assesses the frequency and severity of side effects common to rTMS treatment. Severity of individual side effects are rated from 1 (none) to 10 (extreme).	Daily Monday-Friday throughout study (4 weeks)
Toronto Side Effects Scale (1 week) (TSES)	The Toronto Side Effects Scale measures frequency and severity of a variety of side effects over the past week. Frequency and severity of each symptom are rated on a scale of 1 - 5, with higher scores corresponding to more frequent/severe symptoms.	Administered at baseline, halfway (week 2) and after rTMS treatment (week 4).

Collaborators and Investigators

• Sponsor: University of Calgary
• Investigators: Principal Investigator: Alexander McGirr, MD PhD, University of Calgary

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2023
• Primary Completion (Actual): May 18, 2023
• Study Completion (Actual): May 18, 2023

Study Registration Dates

• First Submitted: May 6, 2019
• First Submitted That Met QC Criteria: May 10, 2019
• First Posted (Actual): May 14, 2019

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 8, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Pregnancy Complications; Puerperal Disorders; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Depression; Depressive Disorder; Depression, Postpartum
• Other Study ID Numbers: REB18-1175

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.: Yes