Chronotherapy for Perinatal Depression

Recruiting at 3 trial locations

Overseen By Samantha Meltzer-Brody, MD,MPH

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Rhode Island Hospital

Must not be taking: Photosensitizing medications

Disqualifiers: Psychosis, Bipolar, Seizure, Migraines, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

Duration: 28 weeks

158 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if adding light exposure and a set sleep routine to regular care can reduce depression and anxiety in pregnant women. It targets women aged 18-40 in late pregnancy who have depression. The treatment aims to adjust the body's natural rhythms and stabilize sleep patterns to improve mood. Light exposure is a promising treatment for depression during pregnancy, being easily accessible, effective, affordable, and safe for both mother and child.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that usual care, which may include medication, will be part of the study. It's best to discuss your specific situation with the trial coordinators.

What data supports the effectiveness of the treatment Personalized Integrated Chronotherapy for perinatal depression?

Research shows that disruptions in sleep and daily activity rhythms are linked to worsening depressive symptoms in the perinatal period. Treatments that stabilize these rhythms, like wake therapy, have been found to improve mood in perinatal depression by adjusting sleep timing and melatonin levels. ^{1 2 3 4 5}

Is chronotherapy for perinatal depression safe for humans?

Melatonin, a component often used in chronotherapy, has been studied for sleep problems in children with neurodevelopmental disorders and appears to be safe, with no significant side effects or development of tolerance observed in these studies. However, long-term safety data, especially concerning its use during pregnancy and interactions with other medications, are limited. ^{6 7 8 9 10}

How is Personalized Integrated Chronotherapy different from other treatments for perinatal depression?

Personalized Integrated Chronotherapy is unique because it uses the body's natural biological rhythms to treat depression, involving techniques like sleep deprivation and light therapy to reset the body's internal clock, unlike traditional treatments that primarily rely on medication. ^{11 12 13 14 15}

Research Team

Kristina M Deligiannidis, MD

Principal Investigator

Northwell Health

Samantha Meltzer-Brody, MD, MPH

Principal Investigator

University of North Carolina, Chapel Hill

Eligibility Criteria

This trial is for pregnant women aged 18-45 with major depressive disorder, as diagnosed by a specific clinical interview and having a certain depression score. It's not for those with seizure disorders, night shift workers, substance abuse issues, high-risk pregnancies or other primary mental health diagnoses. Participants must speak and read English.

Inclusion Criteria

I am a pregnant woman aged 18-45 with major depression.

Exclusion Criteria

I started taking antidepressants within the last 4 weeks.

Bipolar disorder (because sleep restriction can increase risk of conversion to mania)

Current employment as night shift worker

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either usual care or Personalized Integrated Chronotherapy (PIC) during the 3rd trimester of pregnancy and postpartum

28 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 weeks postpartum

Treatment Details

Interventions

• Personalized Integrated Chronotherapy

Trial Overview The study tests Personalized Integrated Chronotherapy (PIC) plus usual care against usual care alone in treating perinatal depression. PIC includes bright light therapy, sleep phase advance, and sleep stabilization/restriction tailored to each patient's circadian rhythm.

Participant Groups

Group I: Personalize Integrated Chronotherapy Experimental Treatment 1 Intervention

Women in the integrated chronotherapy group receive usual care (medications and/or talk therapy, as above) and also receive a bright light box to sit with every morning for up to 60 minutes as prescribed by the study doctor.

Group II: Usual Care Active Control 1 Intervention

Women in the usual care group receive medications and/or talk therapy. Sleep and light levels are monitored at home with wrist actigraphy during 3rd trimester of pregnancy (weeks 28-40) and weeks 2-6 and18 after the baby is born (postpartum weeks 2-6 and 18).

Who Is Running the Clinical Trial?

Rhode Island Hospital

Lead Sponsor

Trials

275

Recruited

71,400+

University of North Carolina, Chapel Hill

Collaborator

Trials

1,588

Recruited

4,364,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

University of Virginia

Collaborator

Trials

802

Recruited

1,342,000+

Northwell Health

Collaborator

Trials

481

Recruited

470,000+

Findings from Research

In a 12-week trial involving 146 children with neurodevelopmental disorders, melatonin significantly reduced the time it took for children to fall asleep by an average of 37.5 minutes, while also increasing total sleep time by about 22.4 minutes according to parent-reported diaries.

While melatonin improved sleep onset, it resulted in earlier waking times and did not lead to significant improvements in child behavior or family functioning, indicating that while it is safe and tolerable, its overall impact on sleep quality may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial. Gringras, P., Gamble, C., Jones, AP., et al.[2022]

In a 26-week study involving 99 children aged 6 to 15 with neurodevelopmental disorders, melatonin significantly reduced sleep onset latency by an average of 36.7 minutes, showing sustained effects even after treatment ended.

Melatonin treatment also led to improvements in temper upon waking and reduced sleepiness after awakening, with no significant adverse events reported after 16 weeks, indicating it is a safe long-term option for managing sleep problems in these children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term melatonin treatment for the sleep problems and aberrant behaviors of children with neurodevelopmental disorders. Yuge, K., Nagamitsu, S., Ishikawa, Y., et al.[2022]

A follow-up study of 44 children with neurodevelopmental disabilities showed that long-term melatonin therapy was well-tolerated, with no adverse reactions or development of tolerance reported over a period of up to 3.8 years.

Caregivers noted significant improvements in sleep quality, which correlated with better health, behavior, and learning outcomes, suggesting that melatonin can be an effective treatment for children with treatment-resistant circadian rhythm sleep disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness outcome of melatonin therapy in children with treatment-resistant circadian rhythm sleep disorders. Carr, R., Wasdell, MB., Hamilton, D., et al.[2013]

Chronotherapeutics, which involves manipulating sleep-wake cycles and light exposure, has shown promising antidepressant effects, particularly in challenging cases like bipolar depression, where traditional antidepressants often fail.

Recent research has clarified the mechanisms behind chronotherapeutics, linking its efficacy to changes in neurotransmitter systems and the biological clock, suggesting it can be effectively integrated into standard psychiatric treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidepressant chronotherapeutics for bipolar depression. Benedetti, F.[2023]

In a study of 194 bipolar depressed patients, over 60% responded positively to a treatment combining total sleep deprivation and light therapy (TSD + LT), indicating its potential efficacy for depression.

The study found that chronotype, or whether a person is a 'morning' or 'evening' type, significantly influenced treatment response, with evening-type patients showing higher rates of improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronotype influences response to antidepressant chronotherapeutics in bipolar patients. Dallaspezia, S., Suzuki, M., Clara, L., et al.[2019]

Chronotherapy, which includes strategies like light therapy and sleep deprivation, has been shown to effectively reduce depressive symptoms and improve recovery in patients with depression and bipolar disorder.

Recent research indicates that combining chronotherapeutic interventions with pharmacological treatments can enhance efficacy, leading to shorter hospital stays and fewer changes in medication prescriptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of chronotherapy on depressive symptoms. Evidence-based practice. Khalifeh, AH.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Sleep, daily activity rhythms and postpartum mood: A longitudinal study across the perinatal period. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Early versus late wake therapy improves mood more in antepartum versus postpartum depression by differentially altering melatonin-sleep timing disturbances. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Multiple dimensions of sleep are consistently associated with chronically elevated depressive symptoms from late pregnancy to 3 years postnatal in Indigenous and non-Indigenous New Zealand women. [2021]

4. England pubmed.ncbi.nlm.nih.gov

High- versus low-intensity interventions for perinatal depression delivered by non-specialist primary maternal care providers in Nigeria: cluster randomised controlled trial (the EXPONATE trial). [2020]

5. Austria pubmed.ncbi.nlm.nih.gov

Do changes in subjective sleep and biological rhythms predict worsening in postpartum depressive symptoms? A prospective study across the perinatal period. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Long-term melatonin treatment for the sleep problems and aberrant behaviors of children with neurodevelopmental disorders. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Long-term effectiveness outcome of melatonin therapy in children with treatment-resistant circadian rhythm sleep disorders. [2013]

9. England pubmed.ncbi.nlm.nih.gov

Use of melatonin in the treatment of paediatric sleep disorders. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Safety of melatonin in long-term use (?) [2017]

11. England pubmed.ncbi.nlm.nih.gov

Antidepressant chronotherapeutics for bipolar depression. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Prediction of sleep deprivation outcome by diurnal variation of mood. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Chronotype influences response to antidepressant chronotherapeutics in bipolar patients. [2019]

14. England pubmed.ncbi.nlm.nih.gov

Time to put a spotlight on out-patient chronotherapy for depression. [2022]

15. Saudi Arabia pubmed.ncbi.nlm.nih.gov

The effect of chronotherapy on depressive symptoms. Evidence-based practice. [2018]