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

52 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial involves keeping participants with depression awake to see if it temporarily improves their mood. Brain scans will be used to study changes in brain chemistry. The goal is to understand how sleep patterns affect depression and find better treatments. Sleep deprivation has been investigated as a treatment for depression for a long time and is known to produce next-day antidepressant effects.

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 data supports the effectiveness of the treatment Sleep Deprivation for Depression?

Research shows that sleep deprivation can improve mood in about 60% of people with depression, often providing faster results than other treatments. However, the positive effects are usually temporary, and mood may worsen after a recovery night. ^{1 2 3 4 5}

Is sleep deprivation therapy safe for humans?

Sleep deprivation therapy has been studied primarily for depression, and while it can have an antidepressant effect, it may lead to relapses after sleep is resumed. There is no clear evidence of serious safety concerns, but the mechanism of action is not fully understood, and it should be used with caution. ^{1 3 6 7 8}

How does sleep deprivation treatment differ from other treatments for depression?

Sleep deprivation treatment for depression is unique because it involves keeping patients awake for a period of time, either partially or totally, to improve mood, unlike typical treatments that often involve medication. It is particularly useful for patients who do not respond to drugs, and its effects can be seen quickly, although it often requires additional therapy to maintain the benefits. ^{6 7 9 10 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Intervention Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Stony Brook University

Lead Sponsor

Trials

225

Recruited

41,700+

Findings from Research

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]

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 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]

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]

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]

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]

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 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]

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]

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]

References

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

Sleep deprivation as treatment for depression: Systematic review and meta-analysis. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Sleep deprivation and antidepressant treatment. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Periodic sleep deprivation in drug-refractory depression. [2018]

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

Microsleep during partial sleep deprivation in depression. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Polysomnography and criteria for the antidepressant response to sleep deprivation. [2018]

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

Sleep deprivation therapy. [2019]

7. Sweden pubmed.ncbi.nlm.nih.gov

Sleep deprivation therapy. [2013]

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

The biological basis of an antidepressant response to sleep deprivation and relapse: review and hypothesis. [2005]

9. Germany pubmed.ncbi.nlm.nih.gov

[Total and partial sleep deprivation in the treatment of depression: preliminary communication]. [2006]

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

Meta-analysis of sleep deprivation in the acute treatment of bipolar depression. [2022]

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

Usage of Therapeutic Sleep Deprivation: A Survey in Psychiatric Hospitals in Austria, Germany, and Switzerland. [2020]