Propofol + Therapy for Depression

(SWIPED II Trial)

Recruiting at 1 trial location

Overseen By Sarah E Knarr

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must be taking: Antidepressants

Must not be taking: Benzodiazepines, Trazodone, Gabapentin

Disqualifiers: Coronary artery disease, Heart failure, Schizophrenia, Bipolar, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 1-2 weeks

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining brief therapy with propofol (a medication often used for anesthesia) can improve sleep and mental health in older adults with depression. Researchers aim to determine if different doses of propofol, administered a few days apart, affect sleep patterns and mood. Participants will also attend therapy sessions designed to improve insomnia. This trial may suit individuals aged 60 or older who have not found relief from depression with standard antidepressant pills. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop taking my current medications for the trial?

You may need to stop or adjust some medications to participate in the trial. Specifically, you cannot use benzodiazepines over 2 mg/day, trazodone over 50 mg/day, or gabapentin over 600 mg/day. If you are taking these medications, you should discuss with the trial team about any necessary changes.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that propofol, a common anesthesia drug, is generally safe for treating depression. A recent study tested deep propofol anesthesia on adults with depression unresponsive to other treatments. The results indicated it was feasible and well-tolerated by these physically healthy individuals. This suggests that propofol can be safely managed under medical supervision for people with depression.

When compared to other treatments like esketamine, propofol had a slightly lower success rate in improving depression symptoms. However, this difference pertains to effectiveness, not safety. The main point is that studies have used propofol safely in depressed patients, with no major safety issues reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using propofol to treat depression because it works in a completely different way than traditional antidepressants. Most antidepressants target neurotransmitter levels like serotonin, but propofol is an anesthetic that induces brain states similar to deep sleep or unconsciousness, potentially resetting brain activity patterns associated with depression. Additionally, while standard antidepressants can take weeks to show effects, propofol could offer rapid relief after just a few infusions. This approach could be a game-changer for patients who haven’t responded well to conventional treatments.

What evidence suggests that this trial's treatments could be effective for depression?

Research has shown that propofol, a common anesthetic, might quickly and effectively reduce depression symptoms. Studies have found that propofol can help people with depression who haven't improved with other treatments. In one study, about 60% of participants experienced significant relief from their depression symptoms after receiving propofol. Researchers believe that propofol helps by improving deep sleep, which is important for mood balance. In this trial, participants will receive either a moderate dose or a low dose of propofol. Both dosing strategies proved effective in previous studies, and the treatment is generally well tolerated. These findings suggest that propofol could be a promising option for improving mood in people with depression. ^{1 6 7 8 9}

Who Is on the Research Team?

Ben Palanca, MD PhD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for older adults with depression. Participants must be able to undergo propofol infusions and brief behavioral therapy for insomnia. There are no gender or ethnic restrictions, but other specific inclusion and exclusion criteria have not been provided.

Inclusion Criteria

I am 60 years old or older.

Provision of signed and dated informed consent form

Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria

Prior reaction to propofol

Resting heart rate < 50 bpm

C-SSRS of 4 or greater (active suicidal ideation with some intent and with/without a specific plan)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Behavioral Therapy

Two sessions of Brief Behavioral Therapy for Insomnia (BBTI) are administered before the propofol infusions

1-2 weeks

2 visits (in-person or virtual)

Treatment

Participants receive two propofol infusions, 2-6 days apart, with concurrent EEG monitoring

1-2 weeks

2 visits (in-person)

Post-Treatment Behavioral Therapy

Two additional sessions of BBTI are administered within 6 weeks after the second infusion

6 weeks

2 visits (in-person or virtual)

Follow-up

Participants are monitored for changes in sleep structure, cognition, anhedonia, and depression up to 10 weeks after the second infusion

10 weeks

Overnight sleep recordings and cognitive assessments

What Are the Treatments Tested in This Trial?

Interventions

• Propofol

Trial Overview The SWIPED Stage II trial tests if low or moderate doses of propofol can improve sleep and mental health in depressed elderly patients when combined with sleep-focused therapy. It's a double-blind study where participants won't know which dose they receive.

How Is the Trial Designed?

Group I: Propofol infusion -moderate dose Experimental Treatment 3 Interventions

Serial propofol infusions to maximally and safely induce unconsciousness and EEG slow waves while minimizing burst suppression. Target brain effect-site concentrations \>2.5 mcg/ml. This will be paired with BBTI.

Group II: Propofol infusion - low dose Active Control 3 Interventions

Serial propofol infusions to safely induce unconsciousness while minimizing EEG slow waves and burst suppression.Target brain effect-site concentration of 1-2 mcg/ml. This will be paired with BBTI.

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6276046/

Propofol for Treatment-Resistant Depression: A Pilot Study This study provides the first evidence suggesting that propofol, a widely available anesthetic agent, has rapid and long-lasting antidepressant effects. Future ...

2. medrxiv.org medrxiv.org/content/10.1101/2023.09.12.23294678v1.full-text

Propofol for treatment resistant depression: A randomized ... Both low- and high-dose infusions were well tolerated, and the protocols used were effective in maintaining the blind. Depression, anxiety ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04680910

Slow Wave Induction by Propofol to Eliminate Depression ... Our hypothesis is that targeted propofol infusion in treatment-resistant depressed patients will induce slow wave activity during sedation and augment ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39417860/

Immediate effects of propofol on mood: a randomized ... Cumulative changes in mood states observed with repeated infusions suggest that propofol engages adaptive mechanisms in mood circuitry.

5. bmjopen.bmj.com bmjopen.bmj.com/content/14/5/e087516

Propofol enhancement of slow wave sleep to target the ... We hypothesise that propofol infusions will enhance SWS and improve depression in older adults with LL-TRD. This hypothesis has been supported by a recent ...

6. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT04680910?term=propofol,++EEG&cond=treatment+resistant+depression&draw=2&rank=1

Slow Wave Induction by Propofol to Eliminate Depression ... Our hypothesis is that targeted propofol infusion in treatment-resistant depressed patients will induce slow wave activity during sedation and augment ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032724015301

Efficacy and safety of esketamine versus propofol in ... Compared to propofol-ECT, esketamine-ECT also had higher depression response (80 % vs. 70 %; p = .06) and remission (65 % vs. 55 %; p = .11) ...

8. medrxiv.org medrxiv.org/content/10.1101/2023.09.12.23294678v1.full.pdf

Propofol for treatment resistant depression The primary and secondary depression outcome measures were the 24-item Hamilton Depression Rating Scale (HDRS-24) and the Patient Health.

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40978474/

Safety and efficacy of esketamine combined with propofol ... The present study hypothesizes that 1) adjunctive esketamine during ECT will produce greater improvement in depressive symptoms compared to placebo; 2) the ...