Sleep Deprivation for Depression

Overseen By Christine DeLorenzo, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stony Brook University

Must not be taking: Stimulants, Antidepressants, Beta-blockers, others

Disqualifiers: Suicide risk, Psychosis, Physical illness, others

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

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how changes in sleep patterns might affect depression. Participants will stay awake for one night (a process known as Sleep Deprivation) to determine if this temporarily improves depression symptoms. Researchers will use brain scans to study brain chemistry during this process. Individuals with depression who frequently experience low moods and trouble sleeping may be a good fit for this trial. Afterward, participants with depression will receive free antidepressant medication. As an unphased trial, this study provides a unique opportunity to contribute to understanding the link between sleep and depression.

Will I have to stop taking my current medications?

Yes, you will need to stop taking medications that affect glutamate levels or circadian rhythms, such as stimulants, anti-epileptics, antidepressants, beta-blockers, hypnotics, melatonin, or medications with glutamateric or GABAergic actions, at least 4 weeks before the study and throughout its duration.

What prior data suggests that this technique is safe for individuals with depression?

Research shows that insufficient sleep can lead to health problems. Studies have found that lack of sleep increases the risk of depression, irritability, and anxiety. It can also cause forgetfulness and unclear thinking. Although these effects might sound concerning, this study involves a controlled and short-term period of sleep deprivation. The risks from missing just one night of sleep are generally low compared to long-term sleep loss. This means the treatment is usually manageable for short periods, as in this study. However, participants should be aware of these possible short-term effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Sleep deprivation is unique because it offers a rapid-acting alternative to traditional depression treatments, which often include medications like SSRIs and therapy that can take weeks to show effects. Unlike these standard treatments, sleep deprivation can produce noticeable improvements in mood within just one day. Researchers are excited about this approach because it bypasses the slow onset of action typical of most antidepressants, offering a potential quick relief for patients who need immediate support.

What evidence suggests that sleep deprivation might be an effective treatment for depression?

Research has shown that staying awake for an entire night, a method tested in this trial, can temporarily improve depression symptoms in 40–60% of people with depression. This mood boost typically lasts less than a day. Studies have found that sleep deprivation affects mood more than it impacts thinking or physical abilities, suggesting a strong connection between sleep and mood. Although staying awake might seem like an unusual treatment, it underscores the close link between sleep and depression. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This study is for adults over 18 with Major Depressive Disorder (MDD) currently experiencing a major depressive episode. Participants must be able to consent, sign a form, and score at least 29 on the MADRS. They can't join if they consume too much caffeine or alcohol, have irregular sleep/wake cycles, are pregnant/lactating/planning pregnancy, have MRI/PET scan contraindications, use certain medications/substances including nicotine or are at risk of suicide.

Inclusion Criteria

Consent form signed

Score of at least twenty-nine on the MADRS (depressed participants only)

I have been diagnosed with major depressive disorder and am currently experiencing a major depressive episode.

Exclusion Criteria

Any PET contraindications, including if study imaging will result in the participant receiving greater exposure than the research limit, or if participant is currently breastfeeding

Participant considered at significant risk for suicide

Any MRI contraindications, including metal implants, pacemaker, metal prostheses, orthodontic appliances, or presence of shrapnel that are contraindicated for MRI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Assessment

Participants undergo initial assessment of circadian phase and brain chemistry using PET scans and melatonin measurements

8 weeks

4 overnight stays (in-person)

Sleep Deprivation Therapy

Participants undergo sleep deprivation therapy followed by melatonin and depression severity assessments

1 week

2 overnight stays (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sleep Deprivation

Trial Overview

The trial investigates how disrupting the sleep/wake cycle affects depression by keeping participants awake for one night. It aims to understand circadian rhythm's role in depression and uses brain scans to study brain chemistry changes. Afterward, depressed participants receive free antidepressant medication.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Stony Brook University

Lead Sponsor

Trials

225

Recruited

41,700+

Published Research Related to This Trial

Sleep deprivation (SD) shows a mean response rate of 47.6% in treating bipolar depression (BPD) based on a systematic review of 15 studies involving 384 patients, indicating it can be an effective intervention.

The efficacy of SD is significantly enhanced when used alongside adjunctive pharmacotherapy, with response rates of 59.4% for those on medication compared to 27.4% for those not, suggesting that combining these treatments may improve outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of sleep deprivation in the acute treatment of bipolar depression. Gottlieb, JF., Goel, N., Chen, S., et al.[2022]

A study involving 93 depressed patients demonstrated that sleep deprivation (SD) can provide therapeutic benefits for endogenous depression, particularly in those with severe symptoms, with effects observable after at least 36 hours.

Partial sleep deprivation, which involves waking patients during the second half of the night, offers similar benefits to total sleep deprivation while being easier for patients to tolerate and implement in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Total and partial sleep deprivation in the treatment of depression: preliminary communication]. Schilgen, B., Bischofs, W., Blaszkiewicz, F., et al.[2006]

Therapeutic sleep deprivation (SD) is recommended by 61.3% of psychiatric hospitals in Austria, Germany, and Switzerland for treating conditions like major depressive disorder, but nearly two-thirds of these hospitals have not used it in the past year, indicating a gap between recommendation and practice.

While SD is considered effective and is often used alongside other therapies, there are concerns about side effects such as hypomania and manic episodes, and the lack of large controlled studies limits its broader acceptance and use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usage of Therapeutic Sleep Deprivation: A Survey in Psychiatric Hospitals in Austria, Germany, and Switzerland. Winkler, D., Spies, M., Al-Resheg, Y., et al.[2020]

In a study of 12 patients with major depression, short phases of sleep (microsleep) during partial sleep deprivation were found to increase, particularly in the early morning, and were often unrecognized by patients and staff.

Patients who experienced less microsleep during partial sleep deprivation showed significant improvements in mood, cognitive performance, and sleep patterns, suggesting that managing microsleep could enhance the benefits of sleep deprivation in treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microsleep during partial sleep deprivation in depression. Hemmeter, U., Bischof, R., Hatzinger, M., et al.[2019]

Sleep deprivation can be an effective treatment for depressive disorders, particularly in cases where other treatments have failed, but it is typically used alongside other therapies to prevent relapse.

Total sleep deprivation is more effective than partial sleep deprivation, and factors like the timing and duration of sleep deprivation, as well as individual patient characteristics, can influence its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep deprivation therapy. Svestka, J.[2013]

In a 25-day trial involving 18 patients with treatment-resistant depression, periodic sleep deprivation combined with ongoing medication showed better results than medication alone, suggesting a potential enhancement in treatment efficacy.

Some patients experienced rapid recovery after just one or a few sessions of sleep deprivation, indicating that this approach may accelerate remission from depressive episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Periodic sleep deprivation in drug-refractory depression. Dessauer, M., Goetze, U., Tölle, R.[2018]

Acute sleep deprivation (SD) can improve mood in about 60% of depressed patients the following day, making it one of the fastest-acting treatments for depression, even quicker than electroconvulsive therapy.

Despite its mood-enhancing effects, the underlying mechanisms of how sleep deprivation improves mood in depression are still not fully understood, and insomnia remains a significant risk factor for developing depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep deprivation and antidepressant treatment. Voderholzer, U.[2021]

In a study of 23 unmedicated patients with major depression, one night of partial sleep deprivation (PSD) led to a significant mood improvement in 40-60% of participants, indicating that sleep deprivation can temporarily alleviate depressive symptoms.

Different response criteria (30%, 35%, 40%, and 50% reductions in depression scores) were effective in distinguishing between responders and nonresponders to PSD, but no single cutoff was superior, suggesting the need for further research to identify the best measure for assessing antidepressant response to sleep deprivation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polysomnography and criteria for the antidepressant response to sleep deprivation. Clark, CP., Golshan, S.[2018]

Therapeutic sleep deprivation has been shown to have antidepressant effects, supported by numerous studies since its introduction in 1971, making it a potential treatment option for depressive disorders.

Partial sleep deprivation late at night is as effective as total sleep deprivation, offering a simpler and more practical method for inducing wakefulness in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep deprivation therapy. Kuhs, H., Tölle, R.[2019]

Over half of depressed patients show an antidepressant response to sleep deprivation, based on a review of 61 studies involving more than 1,700 subjects.

However, 83% of unmedicated patients who initially responded to sleep deprivation relapse after just one night of sleep, suggesting a potential link between sleep and depression relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The biological basis of an antidepressant response to sleep deprivation and relapse: review and hypothesis. Wu, JC., Bunney, WE.[2005]

A systematic review of 8 controlled studies involving 368 patients found that sleep deprivation (SD) combined with standard treatment did not significantly reduce depressive symptoms compared to standard treatment alone, with a standardized mean difference of -0.29.

Post hoc analysis suggested that excluding elderly patients revealed a significant short-term effect of SD on depressive symptoms, but this effect diminished after two weeks, indicating that while SD may have transient benefits, its overall efficacy compared to other treatments remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep deprivation as treatment for depression: Systematic review and meta-analysis. Ioannou, M., Wartenberg, C., Greenbrook, JTV., et al.[2021]

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Extent and Health Consequences of Chronic Sleep Loss and ...

A meta-analysis of 19 original articles found that partial sleep deprivation alters mood to an even greater extent that it does cognitive or motor functions ( ...

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cdc.gov

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Effect of Inadequate Sleep on Frequent Mental Distress

Inadequate sleep was associated with significantly increased odds of frequent mental distress. Our findings suggest that further research is necessary.

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Bidirectional relationship between sleep and depression

For example, acute sleep deprivation can paradoxically improve depressive symptoms. Thus, it is difficult to conclude whether sleep has beneficial or harmful ...

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Brain EffectsSleep Deprivation Leads to Greater Risk For: Depression; Irritability; Anxiety; Forgetfulness; Fuzzy Thinking. thinking graphic.

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Sleep Deprivation: What It Is, Symptoms, Treatment & Stages

People with chronic sleep deprivation are more likely to develop high blood pressure (hypertension) and high cholesterol (hyperlipidemia).