Open-label Placebo for Depression

(OLP Trial)

Overseen By Tony T Yang, MD, PhD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must not be taking: Psychotropic drugs

Disqualifiers: Psychiatric comorbidities, MRI contraindications, others

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

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a non-deceptive placebo (a treatment without active medication) might help adolescents with mild to moderate depression. The researchers aim to determine if informing teens they are taking a placebo can still foster positive expectations that improve their mood. Participants will be divided into groups: one receiving an open-label placebo with an explanation, one without, and a control group receiving no placebo. Teens aged 13-18 who experience mild to moderate depression and are not currently on medication might be suitable for this study. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could enhance mental health treatments for adolescents.

Will I have to stop taking my current medications?

The trial requires participants to be unmedicated, so you would need to stop taking your current medications to join.

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

Research has shown that open-label placebos (OLPs) are generally safe and well-tolerated for people with major depressive disorder (MDD). One study found that people with MDD who took placebos often felt much better, indicating few serious side effects.

Evidence from multiple studies suggests that OLPs work better when participants receive a supportive explanation about the placebo's purpose. This explanation can enhance the placebo's effectiveness.

Research on placebo treatments in clinical trials for teenagers with moderate to severe depression has demonstrated that these treatments are generally safe, even over extended periods. Therefore, prospective participants can feel more confident about the safety of OLPs. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments because they explore the potential of placebos in a unique way. Unlike standard depression treatments that often involve medications like SSRIs or therapy, this trial investigates open-label placebos, which are placebos given with or without an explanation of their purpose. The novelty lies in testing whether simply knowing you are taking a placebo can still improve symptoms of depression. This approach could lead to safer, cost-effective alternatives with fewer side effects than traditional medications.

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

Research has shown that open-label placebos (OLPs), which are placebos given openly without deception, can help with depression. In this trial, participants may receive an OLP with a clear explanation or without any explanation. Studies indicate that OLPs work better when accompanied by a clear explanation. Reviews of multiple studies have found a small to medium improvement in self-reported depression symptoms with OLPs. Even without a detailed explanation, OLPs can still provide some benefits, though they might not be as strong. Overall, placebos, including OLPs, can help reduce depression symptoms by creating positive expectations, which may influence brain areas related to mood and stress. ^{1 2 6 7 8}

Who Is on the Research Team?

Tony T Yang, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for English-speaking adolescents aged 13-18 with mild to moderate depression who are not currently on medication. They must be under the care of a mental health professional or doctor and willing to give informed consent, along with their guardian if necessary.

Inclusion Criteria

You are a teenager between 13-18 years old, not taking any medication, and experiencing mild to moderate depression. A mental health professional or primary care doctor is aware of your condition.

Fluency in English

Exclusion Criteria

Potential subjects with an inability or unwillingness to give written informed assent whose legal guardian/representative are unable or unwilling to give written informed consent will be excluded and not allowed to enroll in the study.

You have mental health conditions other than anxiety disorder, or have severe thoughts about hurting yourself.

MRI contraindications (ferromagnetic objects on or inside the body, e.g. braces) and pregnancy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

MRI scanning and clinical assessments are performed at baseline

1 week

1 visit (in-person)

Treatment

Participants receive open-label placebo (OLP) treatment for 2 weeks

2 weeks

1 visit (in-person) for MRI and OLP administration

Follow-up

Participants are monitored for changes in depression symptoms and neural connectivity

2 weeks

1 visit (in-person) for follow-up MRI and assessments

What Are the Treatments Tested in This Trial?

Interventions

• Open Label Placebo without Rationale
• Open Label Placebo with Rationale

Trial Overview The study tests the effectiveness of open-label placebos (a 'fake' treatment that participants know doesn't contain active medication) in treating adolescent depression. It explores how positive expectations can activate certain brain networks related to emotion and stress regulation.

How Is the Trial Designed?

Group I: Open Label Placebo Group with Rationale Experimental Treatment 1 Intervention

Group II: Control Active Control 1 Intervention

In the control group, the participants will not be taking any placebos or undergoing any other study-related treatments.

Group III: Open Label Placebo Group without Rationale Active Control 1 Intervention

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials

886

Recruited

677,000+

Published Research Related to This Trial

In a study of 1017 patients with major depressive disorder treated with placebo, key predictors for remission included younger age, less severe depressive symptoms, lower anxiety levels, and shorter duration of the current depressive episode.

The predictive models developed showed modest accuracy (ROC curve areas of 0.6-0.65), suggesting they may help adjust for placebo effects in clinical trials, but are not reliable for predicting remission in individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of remission with placebo using an integrated study database from patients with major depressive disorder. Nelson, JC., Zhang, Q., Deberdt, W., et al.[2015]

A meta-analysis of 101 studies found that using a placebo run-in period before randomization does not reduce the placebo response rate or increase the difference in response between drug and placebo treatments for antidepressants.

The findings suggest that including a placebo run-in period in acute phase efficacy trials for antidepressants offers no significant advantages, as it does not improve drug response rates for either inpatients or outpatients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does a placebo run-in or a placebo treatment cell affect the efficacy of antidepressant medications? Trivedi, MH., Rush, H.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3813004/

Open-Label Placebo for Major Depressive Disorder: A Pilot ... In randomized controlled trials (RCTs), major depressive disorder (MDD) patients treated with double-blind placebos often show substantial improvement.

2. nature.com nature.com/articles/s41598-025-14895-z

Effects of open-label placebos across populations and ... Initial meta-analytic evidence suggests that OLPs delivered with such a suggestive rationale tend to be more effective than those without it.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9228278/

Open-label placebos as adjunctive therapy for patients with ... The present study assessed the efficacy of an open-label placebo (OLP), which was administered concurrently with cognitive-behavioral therapy (CBT).

4. nature.com nature.com/articles/s41598-023-30362-z

Open-label placebos—a systematic review and meta ... The results of the meta-analyses revealed a small to medium OLP effect for self-reported outcomes and no OLP effect for objective outcomes.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04201106

A Neuroimaging Study of Open-label Placebo in ... A recent meta-analysis detected a positive and significant effect of non-deceptive placebos (open-label placebo, OLP) for a series of clinical conditions, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4225200/

A Meta-Analysis Comparing Open-Label versus Placebo ... The present study is to provide whether open-label studies (OLS) may properly foresee the efficacy of randomized, placebo-controlled trials (RCTs)

7. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.2008.08040487

Assessment of Safety and Long-Term Outcomes of Initial ... Our purpose in this study was to evaluate the safety of using placebo as a control in clinical trials involving adolescents with moderate to severe depression.

8. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2019.00407/full

Placebo Effect in the Treatment of Depression and Anxiety The aim of this review is to evaluate the placebo effect in the treatment of anxiety and depression. Antidepressants are supposed to work by ...