A Neuroimaging Study of Open-label Placebo in Depressed Adolescents

Summary

Major depressive disorder (MDD) is the current leading cause of disability worldwide and adolescence is an especially vulnerable period for the onset of depression. Non-pharmacologic approaches are particularly attractive as treatment of adolescent depression due to the elevated risks of side effects related to the use of psychotropic drugs during development. A recent meta-analysis detected a positive and significant effect of non-deceptive placebos (open-label placebo, OLP) for a series of clinical conditions, including adult depression. To the investigators' knowledge, no studies of OLP have been conducted in depressed adolescents to date, although placebo response rates in adolescent depression are especially high, accounting for over 80% of the actual response to antidepressant treatment. The study's main objective is to estimate the effectiveness and understand the mechanism of OLP in depressed adolescents. The central hypothesis is that the mechanism by which OLP exerts its action in adolescent depression is by forming a positive expectation, which activates endogenous mu-opioid receptor (MOR)-mediated neurotransmission in a network of regions implicated in emotion, stress regulation, and the pathophysiology of MDD, namely, the anterior cingulate cortex (ACC) - striato - amygdalo - thalamic network. The hypothesis has been formulated on the basis of published research and preliminary data. The investigators will test the hypothesis by performing structural and functional neuroimaging in 60 untreated 13-18 year-old adolescents with mild to moderate depression. The proposed research is significant, because it is expected to elucidate the mechanism of action of OLP and advance the understanding of the neural underpinnings of positive expectations in adolescent depression.

Conditions

• Depression

Interventions

BEHAVIORAL

Open Label Placebo with Rationale

In the OLP + rationale group, the participants will be prescribed to take placebos for 2 weeks with the standard 4-point accompanying rationale: (1) the placebo effect is powerful, e.g. in clinical trials placebos are roughly 80% as effective as antidepressants; (2) classical conditioning is a possible mechanism for automatic self-healing - meaning that the body can automatically respond to taking placebo pills like Pavlov's dogs who salivated when they heard a bell; (3) placebo-treated patients who are more compliant have better outcomes, therefore the placebos should be taken faithfully; and (4) positive expectations increase placebo effects, but it is OK to have doubts.

BEHAVIORAL

Open Label Placebo without Rationale

In the OLP without rationale group, the adolescents will be asked to take placebos for 2 weeks but they will be told that the pills contain inert substance and do not have any pharmacological effect.

Sponsors & Collaborators

• National Center for Complementary and Integrative Health (NCCIH)

  collaborator NIH

• University of California, San Francisco

  lead OTHER

Principal Investigators

• Tony T Yang, MD, PhD · University of California, San Francisco

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

13 Years

Max Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-05-14

Primary Completion

2032-12-30

Completion

2032-12-30

Countries

• United States

Study Locations