Preventing Depressive Relapse in Pregnant Women With Recurrent Depression

• ClinicalTrials.gov Identifier: NCT03623620
• Recruitment Status: Completed
• First Posted: August 9, 2018
• Last Update Posted: November 21, 2022
• Sponsor: Massachusetts General Hospital
• Collaborators: University of Colorado, Boulder; National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): Lee S. Cohen, MD, Massachusetts General Hospital

Study Description

Brief Summary:

The purpose of this investigation is to conduct a pragmatic effectiveness trial comparing digital mindfulness-based cognitive therapy (MBCT) plus usual care to usual care (UC) only among euthymic pregnant women with recurrent depression treated with antidepressants.

In the supplemental arms we will investigate the prevalence, severity, longitudinal course, correlates, and predictors of suicidal ideation and behavior among women during pregnancy and the postpartum period.

Condition or disease	Intervention/treatment	Phase
Depression; Pregnancy Related; Antenatal Depression	Behavioral: Digital Delivery of Mindfulness-Based Cognitive Therapy	Not Applicable

Detailed Description:

This study will address a significant gap in the evidence regarding effective approaches to prevent depressive relapse among women with recurrent depression who maintain euthymia using antidepressants and who wish to conceive or who are pregnant. Relapse rates of depression following antidepressant discontinuation among such women has been established, and the efficacy of MBCT in mitigating relapse risk in pregnant women with recurrent depression compared to UC also has been demonstrated. But the effectiveness of MBCT has not been tested in a definitive trial; the question of whether MBCT can mitigate risk for depressive relapse among pregnant women on antidepressants, including among those who discontinue antidepressants proximate to or during pregnancy, also has not been addressed.

Reproductive age women with recurrent depression and their healthcare providers need to know, first, if a scalable digital non-pharmacologic prevention approach is superior to UC in community settings, and second, whether MBCT can attenuate risk for depressive relapse among those who elect to discontinue maintenance antidepressant treatment proximate to or during pregnancy. Lastly, the capacity to identify which women are most likely to benefit from a non-pharmacologic or pharmacologic approach personalizes the risk benefit decision making process for reproductive age women on antidepressants planning to conceive or who are pregnant.

Investigators will test the relative risk for depressive relapse and reduction of symptom burden between women randomized to digital MBCT or UC, explore the specific benefit of MBCT relative to antidepressant discontinuation, and determine whether a treatment selection algorithm can predict whether MBCT or UC will work best for a specific participant.

The supplemental arms of this study will further investigate suicidal ideation and behavior in a perinatal population to better understand the prevalence, severity, longitudinal course, correlates and predictors of suicidal ideation and behavior among women during pregnancy and in the postpartum period.

Investigators will use a mixed methods approach of both cross-sectional and longitudinal study designs to characterize a real-world population of pregnant and postpartum women who have endorsed suicidality. Investigators will also use qualitative interviews, self-report instruments, and medical records to explore the extent to which community healthcare professionals providing care to perinatal women report the knowledge base and requisite skills to address suicidal ideation and behavior in this population.

MMB for Moms delivers digitally both the content and structure of in-person MBCT, and may be a promising intervention for pregnant women with suicidal ideation. Investigators will also explore the safety, feasibility, and acceptability of enrolling pregnant women with any reports of suicidal ideation or behavior in a proof of concept randomized controlled trial comparing MMB for Moms to enhanced usual care.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1011 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Preventing Depressive Relapse in Pregnant Women With Recurrent Depression
• Actual Study Start Date: March 12, 2019
• Actual Primary Completion Date: March 21, 2022
• Actual Study Completion Date: March 21, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Digital delivery of MBCT (Mindful Mood Balance for Moms); Subjects will receive digital delivery of mindfulness-based cognitive therapy (Mindful Mood Balance for Moms) for 12 weeks, along with the usual care they would receive from their provider.	Behavioral: Digital Delivery of Mindfulness-Based Cognitive Therapy; 12-week program that emphasizes mindfulness and cognitive behavioral skills
No Intervention: Usual Care; Subjects will receive only usual care, the care they would normally receive from their community provider, for 12 weeks.

Outcome Measures

Primary Outcome Measures :

1. Time to relapse [ Time Frame: Enrollment to 6 months postpartum ]
   Time to relapse will be determined through diagnosis of a major depressive episode using the mood module of the Mini-International Neuropsychiatric Interview (MINI).
2. Depressive symptom burden [ Time Frame: Enrollment to 6 months postpartum ]
   Depressive symptom burden will be determined through scores on the Patient Health Questionnaire (PHQ-9) administered as part of the monthly self-report questionnaires

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Females
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Pregnant women
• Ages 18 or older
• History of recurrent major depression prior to pregnancy (at least 2 prior episodes, one of which may be currently treated)
• Euthymic or with residual symptoms (PHQ-9 ≤ 9)
• No depressive relapse since last menstrual period
• Currently or recently received antidepressants (within the three months prior to last menstrual period)
• Presence of ongoing community provider

Exclusion Criteria:

• Diagnosis of bipolar or psychotic disorder
• Active mania, psychosis, or substance abuse (within the last 6 months)
• Immediate risk of self-harm
• Non-English speaking

Inclusion and exclusion criteria for the participants in the supplemental arms of the study differ from the main study and are as follows:

Arm 1 Aim 1a

Inclusion Criteria:

• Pregnant women (prior to 16 weeks gestation)
• Age 18 or older
• Presence of an ongoing community prescriber / provider
• Suicidal ideation as noted by item #9 of the PHQ-9
• History of recurrent depression, dysthymia or subsyndromal depression

Exclusion Criteria:

• Diagnosis of bipolar or psychotic disorder
• Mania, psychosis, or active substance abuse (within the last 6 months for substance abuse)
• Non-English speaking

Arm 1 Aim 1b

Inclusion Criteria:

• Age 18 or older
• Current prenatal healthcare provider of a participant enrolled in Arm 1 Aim 1a

Exclusion Criteria:

• Non-English speaking

Arm 1 Aim 1c

Inclusion Criteria:

• Pregnant women
• Age 18 or older
• Self-reported history of major depressive disorder
• Suicidal ideation as noted by item #9 of the PHQ-9

Exclusion Criteria:

• Non-English speaking

Arm 2

Inclusion Criteria:

• Pregnant women (prior to 16 weeks gestation)
• Age 18 or older
• History of recurrent major depression prior to pregnancy (at least two prior episodes, one of which may be currently treated)
• Euthymic or with residual symptoms (PHQ-9 </=9)
• Presence of an ongoing community prescriber / provider
• Current suicidal ideation as noted by item #9 of the PHQ-9 or past suicidal ideation as noted by item A3g on the MINI mood module

Exclusion Criteria:

• Diagnosis of bipolar or psychotic disorder
• Mania, psychosis, or active substance abuse (within the last 6 months for substance abuse)
• Non-English speaking

Contacts and Locations

Locations

United States, Colorado

University of Colorado Boulder

Boulder, Colorado, United States, 80309

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

University of Colorado, Boulder

National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Lee S Cohen, MD; Massachusetts General Hospital
• Principal Investigator: Sona Dimidjian, PhD; University of Colorado, Boulder

More Information

Publications:

Cohen LS, Altshuler LL, Harlow BL, Nonacs R, Newport DJ, Viguera AC, Suri R, Burt VK, Hendrick V, Reminick AM, Loughead A, Vitonis AF, Stowe ZN. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA. 2006 Feb 1;295(5):499-507. doi: 10.1001/jama.295.5.499. Erratum In: JAMA. 2006 Jul 12;296(2):170.

Dimidjian S, Goodman SH, Felder JN, Gallop R, Brown AP, Beck A. Staying well during pregnancy and the postpartum: A pilot randomized trial of mindfulness-based cognitive therapy for the prevention of depressive relapse/recurrence. J Consult Clin Psychol. 2016 Feb;84(2):134-45. doi: 10.1037/ccp0000068. Epub 2015 Dec 14.

• Responsible Party: Lee S. Cohen, MD, Director, Center for Women's Mental Health, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03623620
• Other Study ID Numbers: 2018P001472; R01MH117253 ( U.S. NIH Grant/Contract )
• First Posted: August 9, 2018
• Last Update Posted: November 21, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data will be shared via the National Database for Clinical Trials related to Mental Illness (NDCT) every 6 months after enrollment begins, and before publication. In addition, de-identified data and accompanying documentation describing and referencing all variables will be available for use by other investigators upon request.
• Supporting Materials: Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: Data will become available 6 months after study start-up and will continue to be available throughout the study.
• Access Criteria: Interested investigators will be asked to submit a proposal form, which will be reviewed by the principal investigator for scientific integrity and adherence to ethical guidelines.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Lee S. Cohen, MD, Massachusetts General Hospital:

Depression; Pregnancy; Antidepressants; Mindfulness; Medication use during pregnancy; Depression Relapse; Suicidal ideation

Additional relevant MeSH terms:

Recurrence; Depression; Depressive Disorder; Behavioral Symptoms; Mood Disorders; Mental Disorders; Disease Attributes; Pathologic Processes