Major Depressive Disorder, Sleep-disordered Breathing
Conditions
Brief summary
The goal of this study is to understand the contribution of sleep-disordered breathing (SDB) to one of the most common and debilitating adverse pregnancy outcomes, perinatal depression. The study is a randomized trial to test the efficacy of positive airway pressure (PAP) on sleep and depression symptoms in perinatal women. Participants will be pregnant women with depression and sleep-disordered breathing. Participants will be randomly assigned to receive either PAP therapy (PAP group) or treatment as usual within obstetrics (TAU group). Mood and sleep assessments will be completed at baseline, after 1 week of enrollment, and monthly thereafter through 12 weeks postpartum. Cortisol will be measured using saliva collection at baseline and again 8 weeks later.
Interventions
Positive airway pressure therapy entails use of a machine that blows pressurized room air through the airway (via a mask or nasal pillows, worn on the face) at a sufficient pressure to keep the upper airway open. The pressurized air acts as a splint. Participants randomized to PAP treatment will be offered PAP therapy using an auto-titrating device.
Sponsors
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* 20-32 weeks gestation with a single, live fetus * meet criteria for major depressive disorder per the Structured Clinical Interview for DSM-V (SCID) * respiratory distress index (RDI; includes apneas, hypopneas, and respiratory effort-related arousals)≥5 per ambulatory assessment plus apnea symptoms (snoring, witnessed apnea, daytime sleepiness, sleep disturbance, snort arousals) * stable dose (for ≥8 weeks) of a selective serotonin reuptake inhibitor (SSRI) OR free of all antidepressant medications past 4 weeks * obstetrics care is at the University of Michigan, and the woman plans on delivering her baby at the University of Michigan
Exclusion criteria
* Diagnosis of bipolar disorder, posttraumatic stress disorder, schizophrenia or psychosis, dissociative disorders, eating disorder, obsessive-compulsive disorder, somatic symptom and related disorders, substance use disorder, panic disorder, agoraphobia per DSM-V * diagnosis of, or suspicion for, narcolepsy or REM behavior disorder * current SDB treatment; medical conditions for which PAP is contraindicated (e.g., pneumothorax, pneumocephalus, recent trauma, recent surgery) * evidence of risk for drowsy driving (excessive daytime sleepiness plus history of motor vehicle accident or near miss due to sleepiness, fatigue, or inattention in past 12 months).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hamilton Rating Scale for Depression (HRSD) Score, Minus the Sleep Item | Baseline to 8 weeks after baseline, and at 12 weeks postpartum | Change in clinician-rated depression severity and symptoms, excluding the items which measure sleep. Total score range: 0-46. Higher scores represent more severe depression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Edinburgh Postnatal Depression Scale Score | Baseline to 8 weeks after baseline, and at 12 weeks postpartum | Change in a self-report measure of depression symptoms and severity. Total scores range from 0 to 27; higher scores indicate more severe depression. |
| Change in Pittsburgh Sleep Quality Index Score | Baseline to 8 weeks after baseline, and at 12 weeks postpartum | Change in a measure of sleep quality. Total scores range from 0 to 21. Higher scores indicate worse sleep quality. |
| Change in Epworth Sleepiness Scale (ESS) Score | Baseline to 8 weeks after baseline, and at 12 weeks postpartum | Change in a measure of excessive daytime sleepiness. Scores range from 0 to 25. Higher scores indicate more daytime sleepiness. |
| Change in Salivary Cortisol | Baseline to 8 weeks after baseline | Salivary cortisol is a hormone produced by the adrenal gland. Values are in nmol/L; detectable assay range is 0.33 - 82.77 nmol/L. Higher values indicate higher levels of cortisol. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PAP Group Positive airway pressure (PAP) delivered through an auto-titrating machine, to be used nightly
Positive Airway Pressure (PAP): Positive airway pressure therapy entails use of a machine that blows pressurized room air through the airway (via a mask or nasal pillows, worn on the face) at a sufficient pressure to keep the upper airway open. The pressurized air acts as a splint. Participants randomized to PAP treatment will be offered PAP therapy using an auto-titrating device. | 16 |
| TAU Group Treatment as usual through obstetrics | 13 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | TAU Group | PAP Group | Total |
|---|---|---|---|
| Age, Continuous | 27.31 years STANDARD_DEVIATION 6.32 | 31.44 years STANDARD_DEVIATION 5.39 | 29.18 years STANDARD_DEVIATION 5.95 |
| Edinburgh Postnatal Depression Scale (EPDS) Score, Minus the Sleep Item | 14.15 units on a scale STANDARD_DEVIATION 3.76 | 11.88 units on a scale STANDARD_DEVIATION 3.79 | 12.9 units on a scale STANDARD_DEVIATION 3.89 |
| Epworth Sleepiness Scale (ESS) Score | 8.54 units on a scale STANDARD_DEVIATION 4.16 | 12.44 units on a scale STANDARD_DEVIATION 4.03 | 10.69 units on a scale STANDARD_DEVIATION 4.47 |
| Hamilton Rating Scale for Depression (HRSD) Score, Excluding the Sleep Items | 14.69 units on a scale STANDARD_DEVIATION 3.68 | 15.06 units on a scale STANDARD_DEVIATION 3.87 | 14.9 units on a scale STANDARD_DEVIATION 3.73 |
| Pittsburgh Sleep Quality Index (PSQI) Score | 10.92 units on a scale STANDARD_DEVIATION 3.12 | 9.63 units on a scale STANDARD_DEVIATION 2.99 | 10.21 units on a scale STANDARD_DEVIATION 3.06 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 11 Participants | 18 Participants |
| Salivary cortisol | 33.02 nmol/L STANDARD_DEVIATION 10.82 | 33.07 nmol/L STANDARD_DEVIATION 6.89 | 33.05 nmol/L STANDARD_DEVIATION 8.69 |
| Sex: Female, Male Female | 13 Participants | 16 Participants | 29 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 13 |
| other Total, other adverse events | 10 / 16 | 6 / 13 |
| serious Total, serious adverse events | 3 / 16 | 0 / 13 |
Outcome results
Primary
Change in Hamilton Rating Scale for Depression (HRSD) Score, Minus the Sleep Item
Change in clinician-rated depression severity and symptoms, excluding the items which measure sleep. Total score range: 0-46. Higher scores represent more severe depression.
Time frame: Baseline to 8 weeks after baseline, and at 12 weeks postpartum
Population: Data are not available for 3 participants of the 16 participants started in the PAP group at baseline to 8 weeks. Data are not available for 3 participants of the 16 participants started in the PAP group at baseline to 12 weeks and 2 participants of the 13 participants started in the TAU group at baseline to 12 weeks postpartum.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP Group | Change in Hamilton Rating Scale for Depression (HRSD) Score, Minus the Sleep Item | Baseline to 8 weeks after baseline | -7.62 change in score | Standard Deviation 5.65 |
| PAP Group | Change in Hamilton Rating Scale for Depression (HRSD) Score, Minus the Sleep Item | Baseline to 12 weeks postpartum | -8.21 change in score | Standard Deviation 7.39 |
| TAU Group | Change in Hamilton Rating Scale for Depression (HRSD) Score, Minus the Sleep Item | Baseline to 8 weeks after baseline | -5.92 change in score | Standard Deviation 3.47 |
| TAU Group | Change in Hamilton Rating Scale for Depression (HRSD) Score, Minus the Sleep Item | Baseline to 12 weeks postpartum | -6.18 change in score | Standard Deviation 6.51 |
Comparison: Baseline to 8 weeks after baselinep-value: 0.367t-test, 2 sided
Comparison: Baseline to 12 weeks postpartump-value: 0.48t-test, 2 sided
Secondary
Change in Edinburgh Postnatal Depression Scale Score
Change in a self-report measure of depression symptoms and severity. Total scores range from 0 to 27; higher scores indicate more severe depression.
Time frame: Baseline to 8 weeks after baseline, and at 12 weeks postpartum
Population: Data for the baseline to 12 weeks postpartum analysis are not available for 3 participants of the 13 participants started in the TAU group and for 2 participants of the 16 participants started in the PAP group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP Group | Change in Edinburgh Postnatal Depression Scale Score | Baseline to 8 weeks after baseline | -4.13 score on a scale | Standard Deviation 3.11 |
| PAP Group | Change in Edinburgh Postnatal Depression Scale Score | Baseline to 12 weeks postpartum | -3.00 score on a scale | Standard Deviation 3.88 |
| TAU Group | Change in Edinburgh Postnatal Depression Scale Score | Baseline to 8 weeks after baseline | -2.23 score on a scale | Standard Deviation 3.51 |
| TAU Group | Change in Edinburgh Postnatal Depression Scale Score | Baseline to 12 weeks postpartum | -5.00 score on a scale | Standard Deviation 5.85 |
Comparison: Baseline to 8 weeks after baselinep-value: 0.136t-test, 2 sided
Comparison: Baseline to 12 weeks postpartump-value: 0.324t-test, 2 sided
Secondary
Change in Epworth Sleepiness Scale (ESS) Score
Change in a measure of excessive daytime sleepiness. Scores range from 0 to 25. Higher scores indicate more daytime sleepiness.
Time frame: Baseline to 8 weeks after baseline, and at 12 weeks postpartum
Population: Data are not available for 2 participants of the 16 participants started in the PAP group at baseline to 8 weeks and 3 participants of the 13 participants started in the TAU group at baseline to 8 weeks. Data are not available for 2 participants of the 16 participants started in the PAP group at baseline to 12 weeks and 3 participants of the 13 participants started in the TAU group at baseline to 12 weeks postpartum.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP Group | Change in Epworth Sleepiness Scale (ESS) Score | Baseline to 8 weeks after baseline | -2.14 change in score | Standard Deviation 4.14 |
| PAP Group | Change in Epworth Sleepiness Scale (ESS) Score | Baseline to 12 weeks postpartum | -2.14 change in score | Standard Deviation 4.15 |
| TAU Group | Change in Epworth Sleepiness Scale (ESS) Score | Baseline to 8 weeks after baseline | -1.00 change in score | Standard Deviation 5.54 |
| TAU Group | Change in Epworth Sleepiness Scale (ESS) Score | Baseline to 12 weeks postpartum | -1 change in score | Standard Deviation 5.54 |
Comparison: Baseline to 8 weeks after baselinep-value: 0.568t-test, 2 sided
Comparison: Baseline to 12 weeks postpartump-value: 0.568t-test, 2 sided
Secondary
Change in Pittsburgh Sleep Quality Index Score
Change in a measure of sleep quality. Total scores range from 0 to 21. Higher scores indicate worse sleep quality.
Time frame: Baseline to 8 weeks after baseline, and at 12 weeks postpartum
Population: Data for 2 participants of the 16 participants started in the PAP group are not available in the baseline to 8 weeks after baseline analysis and data for 3 participants from the 13 participants started in the TAU group are not available in the baseline to 8 weeks after baseline analysis. Data from 3 participants from the 13 participants started in the TAU group and 2 participants of the 16 participants started in the PAP group are not available in the baseline to 12 weeks analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP Group | Change in Pittsburgh Sleep Quality Index Score | Baseline to 8 weeks after baseline | -1.64 score on a scale | Standard Deviation 3.1 |
| PAP Group | Change in Pittsburgh Sleep Quality Index Score | Baseline to 12 weeks postpartum | -1.29 score on a scale | Standard Deviation 3.67 |
| TAU Group | Change in Pittsburgh Sleep Quality Index Score | Baseline to 12 weeks postpartum | -1.8 score on a scale | Standard Deviation 4.16 |
| TAU Group | Change in Pittsburgh Sleep Quality Index Score | Baseline to 8 weeks after baseline | -1.80 score on a scale | Standard Deviation 4.16 |
Comparison: Baseline to 8 weeks after baselinep-value: 0.916t-test, 2 sided
Comparison: Baseline to 12 weeks postpartump-value: 0.752t-test, 2 sided
Secondary
Change in Salivary Cortisol
Salivary cortisol is a hormone produced by the adrenal gland. Values are in nmol/L; detectable assay range is 0.33 - 82.77 nmol/L. Higher values indicate higher levels of cortisol.
Time frame: Baseline to 8 weeks after baseline
Population: Data are not available for 4 participants of the 16 participants started in the PAP group and 3 participants of the 13 participants started in the TAU group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PAP Group | Change in Salivary Cortisol | -1.23 nmol/L | Standard Deviation 7.23 |
| TAU Group | Change in Salivary Cortisol | 1.38 nmol/L | Standard Deviation 9.98 |
p-value: 0.486t-test, 2 sided