Testing a Non-Deceptive Placebo Intervention for Subclinical Depressive Symptoms

Non-deceptive (open-label) placebos have been shown to reduce negative emotion, stress, anxiety, and depressive symptoms across a range of nonclinical samples. Because the intervention requires explicitly telling participants that the pills contain no active ingredients, participants cannot be blinded to the intervention. This creates an unresolved methodological problem: there is no consensus on the appropriate comparison condition. Some trials use unblinded assessment-only controls, which prioritize transparency but may introduce negative expectancy or demoralization and inflate apparent intervention effects. Others use blinded controls, which may better isolate expectancy mechanisms but raise concerns about incomplete disclosure. Few studies have compared the two within a single randomized design.

This trial is a remote, parallel-group randomized controlled trial in young adults with subclinical depressive symptoms. Eligible participants are randomized in blocks of 30 to one of three arms, with allocation distributed evenly across conditions. Randomization occurs after eligibility confirmation and before the first live session, because arm assignment determines which enrollment consent form is presented and because the placebo arm requires materials to be mailed in advance.

The study is conducted entirely remotely using Qualtrics for survey administration and Webex for live sessions, across four phases spanning approximately 16-18 days:

Day 0 (Screening): Online screening consent followed by an eligibility survey covering demographics, PHQ-8, and feasibility items.

Day 1 (Enrollment, ~60 min, Webex Session 1): Eligibility is confirmed, participants complete arm-specific enrollment consent, and a battery of individual difference measures assessing worry, trait anxiety, dispositional optimism, personality, emotion regulation, and implicit theories of anxiety, depression, and trauma.

Days 3-5 (Baseline/Time 1, ~60 min, Webex Session 2): All participants complete baseline outcome measures, then receive a standardized presentation on the prevalence of stress, anxiety, and depressive symptoms. Participants in the non-deceptive placebo arm then receive the intervention: two brief psychoeducational videos on placebos and non-deceptive placebo effects with comprehension and expectancy items, followed by instructions for twice-daily pill intake over the following two weeks and for completing a brief daily pill-tracking survey. Participants in the unblinded control arm are informed of their control status. Participants in the two control arms receive no placebo psychoeducation and no pills.

Days 16-18 (Endpoint/Time 2, ~60 min, Webex Session 3): All participants complete endpoint outcome measures and open-ended feedback items and receive a full debriefing describing the study conditions and their own assignment. Participants in the blinded control arm are explicitly informed that the study involved incomplete disclosure and given the rationale, and may request withdrawal of their data.

The primary analysis will use a mixed model for repeated measures with planned orthogonal contrasts: the non-deceptive placebo arm versus the average of the two control arms (Aim 1), and the blinded versus unblinded control arms (Aim 2).