Neurobiological Underpinnings of Placebo Response in Depression

Phase 4

Completed

• Conditions: Depression
• Interventions: Drug: Welbutrin XL; Drug: Placebo

• Registration Number: NCT02562430
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

In summary, the proposed research is novel with respect to design, technology, and its multi-level integration probing psychological and neurobiological constructs assumed to be crucially implicated in placebo response and has significant clinical and research implications for the future. Specifically, the future implications include: 1) identification of biomarkers and biosignatures of placebo responders, 2) new possibilities to understanding and manipulating the system, 3) possibly decreasing or eliminating a major confounder in clinical trials and drug development, and 4) refining treatments with novel drugs that decrease (in clinical trial) or increase (in clinical practice) the placebo response.

Detailed Description

The objective of this pilot study is to investigate possible dopaminergic mechanisms underlying the placebo response in MDD.

We expect that mesolimbic DA mechanisms implicated in reward anticipation, reinforcement learning, and expectation play a critical role in mediating placebo responses in MDD. A better understanding of the neurobiological basis of placebo has enormous potential on different levels. On a clinical level, the understanding of placebo mechanisms could lead to a number of applications for therapeutic purposes, such as developing drugs that could enhance the effects of a therapeutic relationship or accelerate the onset of action of an antidepressant by manipulating the placebo-related mechanisms, even if the patient is hopeless or severely anhedonic. On a level of clinical trial innovation, if we confirm the role of dopamine in placebo response and we comprehend how the placebo response mechanistically takes place, this could lead to developing new drugs that could block the placebo effects in clinical trial participants and greatly decrease if not eliminate the placebo effect nested even in those subject who are drug responders, therefore increasing the effect size and decreasing the sample size of studies. Moreover if we can identify biosignatures of placebo effect and use them to predict response, we could potentially enrich samples with subjects who are less likely to be placebo responders and again this would result in increased signal detection in a clinical trial. Finally, with this initial study we plan to lay the foundation for other studies to investigate how this dopaminergic circuitry is affected by other treatments, such as psychotherapy, and what are the changes that are similar or different between antidepressants, placebo and specific forms of psychotherapy, transcranial magnetic stimulation, electroconvulsive therapy or deep brain stimulation.

Study Timeline

• Study First Submitted: 2015-09-25
• Study First Submitted QC: 2015-09-25
• Study First Posted: 2015-09-29
• Study Start: 2016-08
• Primary Completion: 2022-08
• Study Completion: 2022-08
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-06
• Last Update Posted: 2022-09-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 73

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active Treatment	Welbutrin XL	12.5 % will be randomized to Welbutrin XL in phase 1 of the study.
Placebo Group	Placebo	87.5% will be randomized to receive placebo in phase 1 of the study.

Primary Outcome Measures

Name	Time	Method
HAM-D 32	8 weeks

Secondary Outcome Measures

Name	Time	Method
Clinical Global Impressions	8 weeks

Trial Locations

Locations (1)

Depression Clinical and Research Program at Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States