Propofol-Induced Sleep for Depression

Overseen By Elliott Kraenzle

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must be taking: Antidepressants

Must not be taking: Benzodiazepines, Trazodone, Gabapentin

Disqualifiers: Coronary artery disease, Heart failure, Dementia, others

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

Compensation: Varies

Number of Visits: 3

Duration: 1-2 weeks

15 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you do not use benzodiazepines over 2 mg/day, trazodone over 50 mg/day, or gabapentin over 600 mg/day. If you are taking these medications above these amounts, you may need to adjust your dosage.

What data supports the effectiveness of the drug Propofol for treating depression?

Research on sleep deprivation shows that it can improve depressive symptoms in many patients, although the effects are often temporary. Since Propofol is used to induce sleep, it might have similar effects by altering sleep patterns, which could potentially help with depression. ^{1 2 3 4 5}

Is propofol generally safe for use in humans?

Propofol is generally considered safe for use in humans, but it can cause some serious side effects like low blood pressure, breathing problems, and a rare condition called propofol infusion syndrome. It is widely used for anesthesia and sedation, and its safety profile is well established, though caution is advised, especially in high-risk patients. ^{6 7 8 9 10}

How does the drug Propofol differ from other treatments for depression?

Propofol is unique in treating depression because it enhances slow wave sleep (deep sleep), which is often deficient in older adults with depression. Unlike traditional antidepressants that target neurotransmitters, Propofol induces sleep patterns similar to natural non-rapid eye movement sleep, potentially improving both sleep quality and depression symptoms. ^{11 12 13 14 15}

What is the purpose of this trial?

Our hypothesis is that targeted propofol infusion in treatment-resistant depressed patients will induce slow wave activity during sedation and augment subsequent sleep slow wave activity. We will recruit 15 participants for this open label single arm Phase I trial. All participants will undergo two propofol infusions 2-6 days apart, with each infusion maximizing expression of EEG slow waves. To minimize bias, there will be no specific gender or ethnic background consideration for enrollment. This will be a single site investigation at Washington University Medical Center.

Research Team

Ben Palanca, MD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for English-speaking individuals aged 60 or older with a history of treatment-resistant major depressive disorder, which means depression that hasn't improved after trying at least two different oral antidepressants. Participants must be cognitively sharp (MOCA score ≥ 23) and not have severe heart issues, propofol allergies, high suicide risk, extreme obesity (BMI ≤ 35), or current treatments like ECT/TMS or active vagal nerve implants.

Inclusion Criteria

I am 60 years old or older.

I have major depression that didn't improve with at least two different antidepressants.

Exclusion Criteria

Your body mass index (BMI) is higher than 35.

I have symptoms of heart disease.

You have a score of 4 or higher on a test called Columbia-Suicide Severity Rating Scale (C-SSRS).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two propofol infusions 2-6 days apart, with EEG monitoring to maximize slow wave activity

1-2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for changes in sleep architecture and cognitive function using at-home EEG recordings and cognitive assessments

3 weeks

Multiple at-home recordings, 1-2 visits (in-person)

Long-term Follow-up

Participants are assessed for changes in depression, anhedonia, and suicidality up to 10 weeks after the second infusion

10 weeks

Treatment Details

Interventions

• Propofol

Trial Overview The SWIPED trial is testing whether propofol can help treat depression by inducing slow wave activity in the brain during sedation. This Phase I study involves giving participants two doses of propofol a few days apart to see if it improves their EEG slow waves and subsequent sleep quality. It's an open-label trial without placebo control conducted at Washington University Medical Center.

Participant Groups

Group I: Propofol infusion Experimental Treatment 3 Interventions

Serial propofol infusions to maximally and safely induce unconsciousness and EEG slow waves while minimizing burst suppression.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

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]

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]

Propofol is a safe and effective anesthetic agent, with induction doses of 2-2.5 mg/kg and maintenance doses of about 9 mg/kg per hour, leading to rapid and predictable emergence from anesthesia.

The use of propofol alone can significantly reduce post-induction hypotension and minimize apnea when pre-induction hyperventilation is avoided, making it a reliable choice for anesthesia without major complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propofol as an intravenous agent in general anesthesia and conscious sedation. McNeir, DA., Mainous, EG., Trieger, N.[2018]

A study analyzing 1651 adverse event reports related to propofol from the US FDA database identified 363 significant adverse reaction signals, with anaphylactic shock, hypotension, and propofol infusion syndrome being the most common.

The findings highlight that propofol can cause a wide range of adverse reactions affecting various body systems, indicating that clinicians should exercise caution when using this anesthetic, as many reactions are not listed in the drug's official insert.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propofol-associated serious adverse events: an analysis of the FAERS database. Xuan, G., Zhang, Y., Cui, J., et al.[2023]

Propofol is a short-acting intravenous anesthetic that is widely used for sedation in mechanically ventilated patients in the ICU due to its rapid onset and termination of action.

While propofol has a well-established safety profile, clinicians should be aware of potential adverse reactions associated with its use, emphasizing the importance of monitoring patients during administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propofol for sedation in the intensive care unit: essentials for the clinician. Marinella, MA.[2019]

References

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

Therapeutic use of sleep deprivation in depression. [2022]

2. Denmark pubmed.ncbi.nlm.nih.gov

[Wake therapy for major depression]. [2017]

3. Germany pubmed.ncbi.nlm.nih.gov

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

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

Microsleep during partial sleep deprivation in depression. [2019]

5. Ireland pubmed.ncbi.nlm.nih.gov

Sleep deprivation effects in older endogenous depressed patients. [2019]

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Propofol as an intravenous agent in general anesthesia and conscious sedation. [2018]

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Safety of propofol for conscious sedation during endoscopic procedures in high-risk patients-a prospective, controlled study. [2022]

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Propofol-associated serious adverse events: an analysis of the FAERS database. [2023]

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Propofol for sedation in the intensive care unit: essentials for the clinician. [2019]

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[Drugs for intravenous induction of anesthesia: propofol]. [2022]

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Effect of flumazenil-augmentation on microsleep and mood in depressed patients during partial sleep deprivation. [2022]