Integrated Chronotherapy for Perinatal Depression

Perinatal depression is a common and serious mood disorder that increases morbidity and mortality in new mothers and results in poor infant/child outcomes. Current therapies often fail to produce recovery or are poorly tolerated and many pregnant women seek non-pharmacologic therapy or forgo treatment when non-pharmacologic options are not available. Expectant and new mothers who suffer from circadian rhythm disruption are at risk for perinatal depression. This R34 Pilot Effectiveness Studies and Services Research Grant seeks to test whether an Integrated Chronotherapy (IC) intervention can be implemented in an outpatient psychiatry setting to improve treatment outcomes for patients with perinatal depression. IC is a multicomponent treatment consisting of bright light therapy, sleep phase advance, and sleep stabilization/restriction that targets the Research Domain Criteria (RDoC) constructs of circadian rhythms, sleep-wake behavior, social rhythms, and arousal. We will assess the feasibility, safety, and acceptability of an IC intervention for perinatal depressin by testing the treatment in expectant mothers diagnosed with major depressive disorder during 3rd trimester of pregnancy. We will randomize patients to either: (a) usual care (UC, n = 20) or (b) IC+UC (n = 20). IC+UC will have pregnancy and postpartum components and will be administered via an individualized case formulation approach tailored to each patient. After a baseline assessment, IC will be prescribed during 5 dedicated clinical visits: three during 3rd trimester of pregnancy and 2 in the postpartum period. UC will consist of medication administered by a perinatal psychiatrist and/or psychotherapy. UC will be quantified in both groups to evaluate differences between the IC+UC and UC groups. Mood will be measured in both groups by blinded clinician interview and patient self-report. We will assess the safety profile of the IC intervention with evaluation of side effects/adverse events. Importantly, the study will also examine the putative mechanisms by which IC is hypothesized to work and the "dose" of IC received by patients in the IC+UC group. All participants will wear wrist actigraphy/light monitors continuously during weeks 28-40 of pregnancy and postpartum weeks 2-6 to assess light exposure and sleep duration and timing. Circadian phase (measured with salivary dim light melatonin onset) will be measured at baseline during pregnancy (~30 weeks gestation), at 36 weeks gestation, and at postpartum week 6. This pilot will allow us to refine the IC intervention for future integration into various clinical settings and establish an infrastructue for a larger (R01-scale) trial, including measuring acceptability of IC among UC clinicians and implementing web-based data collection to facilitate data sharing in the planned R01. Perinatal IC could have major public health impact due to the high prevalence of perinatal depression and its negative effects on mothers and their children. This project represents a first step toward achieving this goal, as it will provide the pilot data necessary to prepare for a larger scale intervention study focused on providing non-pharmacologic therapies and improving outcomes for women with perinatal depression.

Study Overview

• Status: Completed
• Conditions: Depression; Postpartum Depression; Major Depressive Disorder
• Intervention / Treatment: Other: Usual Care; Behavioral: Triple Chronotherapy

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

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02904
      • Miriam Hospital Women's Medicine Collaborative

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• pregnant women with a diagnosis of major depressive disorder at 24-28 weeks gestation

Exclusion Criteria:

• active psychosis or suicidality contraindicating outpatient treatment
• bipolar disorder
• seizure disorder
• self report of frequent migraines/headaches precipitated by bright light or sleep deprivation
• preexisting eye/skin disorders contraindicating light therapy
• use of photosensitizing medications
• primary Axis I diagnosis other than MDD (comorbid phobia, generalized or social anxiety disorder allowed)
• high risk pregnancy (e.g., conditions requiring mandatory bed rest or complex medical regimens that will interfere with study participation or conditions where poor infant outcomes are anticipated)
• starting antidepressants within 4 weeks of enrollment
• current employment as shift worker
• current alcohol or drug use disorders
• women whose infants will not be living in the home or who will have a nighttime caregiver
• Pittsburgh Sleep Quality Inventory (PSQI) < 5 (i.e., those who report no sleep complaints during 3rd trimester of pregnancy and for whom an intervention targeting sleep might not be indicated).
• women who do not speak and read English (because the complexity of translating the research instruments is beyond the scope of this project)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual Care; Usual Care will consist of medication administered by a perinatal psychiatrist and/or psychotherapy	Other: Usual Care; UC will consist of medication administered by a perinatal psychiatrist and/or psychotherapy
Experimental: Triple Chronotherapy + Usual Care; triple chronotherapy (TC) will consist of bright light therapy, sleep phase advance, and sleep deprivation/restriction	Other: Usual Care; UC will consist of medication administered by a perinatal psychiatrist and/or psychotherapy; Behavioral: Triple Chronotherapy; triple chronotherapy (TC will consist of bright light therapy, sleep phase advance, and sleep deprivation/restriction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Depression Score	17-item Hamilton Depression score	Change in depression score from 28 weeks of pregnancy to 6 weeks postpartum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep/Circadian Behavior	sleep will be measured with wrist actigraphy and circadian phase will be measured with melatonin onset	Change in Sleep/Circadian Rhythms from 28 weeks pregnancy to 6 weeks postpartum

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side Effects	Systematic Assessment for Treatment Emergent Effects	Pregnancy weeks 33, 36; postpartum weeks 2, 6, 26

Collaborators and Investigators

• Sponsor: Rhode Island Hospital
• Collaborators: National Institute of Mental Health (NIMH); The Depressive and Bipolar Disorder Alternative Treatment Foundation
• Investigators: Principal Investigator: Katherine M Sharkey, MD, PhD, Rhode Island Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): January 15, 2019
• Study Completion (Actual): February 28, 2019

Study Registration Dates

• First Submitted: January 30, 2014
• First Submitted That Met QC Criteria: January 31, 2014
• First Posted (Estimate): February 4, 2014

Study Record Updates

• Last Update Posted (Actual): May 29, 2019
• Last Update Submitted That Met QC Criteria: May 24, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: sleep; depression; major depressive disorder; circadian; postpartum depression; antenatal depression; bright light
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Pregnancy Complications; Puerperal Disorders; Depression; Depressive Disorder; Depression, Postpartum; Depressive Disorder, Major
• Other Study ID Numbers: 540053-2; 1R34MH104377-01A1 (U.S. NIH Grant/Contract)

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: No