Neurobiological Bases of Placebo Response in Major Depressive Disorder

We are doing this research study to find out if people who get better while taking a specific kind of antidepressant medication (a selective serotonin reuptake inhibitor, or SSRI) and people who get better while taking placebo (an inactive substance) have similar chemicals in their brains. Some participants may complete a procedure called Acute Tryptophan Depletion (ATD), which is a way to study the role of serotonin in depression. Some participants may also undergo a magnetic resonance-positron emission tomography (MR-PET) scan.

Study Overview

• Status: Terminated
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Escitalopram 10mg

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Depression Clinical and Research Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Meets diagnostic criteria for Major Depressive Disorder
• Written informed consent
• Men or women aged 18-60 years old
• A score of 18 or greater on the HAMD-28
• Patient must continue to meet criteria for current MDD at baseline. Patients must have Clinical Global Impression Improvement (CGI) scores ≥ 3 (i.e. minimally improved or less) from the screen to the baseline visit
• Agreeing to, and eligible for all procedures (only patients 18-45 will be eligible for MR-PET study)

Exclusion Criteria:

• Pregnant women or women of child bearing potential not using a medically accepted means of contraception
• Patients who are a serious suicide or homicide risk
• Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease, uncontrolled seizure disorder
• The following DSM-IV diagnoses: a) organic mental disorders b) substance use disorders, including alcohol, active within the last year; c) schizophrenia; d) delusional disorder; e) psychotic disorders not elsewhere classified; f) bipolar disorder; g) acute bereavement; h) borderline or antisocial personality disorder i) current primary diagnoses of panic disorder, social phobia, GAD, or OCD (disorders that present as chief complaint and/or have their onset preceding the onset of MDD), l) Patients with mood congruent or mood incongruent psychotic features
• Currently taking any of the following exclusionary medications: antipsychotics, anticonvulsants, mood stabilizers, stimulants, antidepressants, potential antidepressant augmenting agents (e.g., T3, SAMe, St. John's Wort, lithium, buspirone, Omega 3 fatty acids). If it is determined that it is safe to discontinue a medication, the patient will be required to wait a period equivalent to at least 5 half lives of the drug before the screening
• Patients who have taken an investigational psychotropic drug within the last year
• Patients who have not responded to one or more antidepressant trials of adequate doses (e.g., fluoxetine 40 mg/day or higher) and duration (e.g., for six weeks or more) over the past five years, as defined by the MGH-ATRQ
• History of inadequate response or poor tolerability to citalopram or escitalopram
• Any concomitant form of psychotherapy (depression-focused)
• Receiving or have received during the index episode Vagal nerve stimulation, ECT or rTMS, or other somatic antidepressant treatments
• Any reason not listed, determined by the site PI or study clinician, constituting good clinical practice and making participation in the study hazardous
• Contraindications to fMRI scanning and MR-PET scanning (including presence of a cardiac pacemaker or pacemaker wires, metallic particles in the body, vascular clips in the head or previous neurosurgery, prosthetic heart valves, claustrophobia)
• MR-PET-specific exclusion criteria: Patients who are younger than 18 or older than 45 years of age

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; After a screening visit, the patient will undergo a baseline assessment and will be randomized to escitalopram 10mg or placebo.	Drug: Placebo
Experimental: Escitalopram 10mg; After a screening visit, the patient will undergo a baseline assessment and will be randomized to escitalopram 10mg or placebo.	Drug: Escitalopram 10mg; Other Names: Lexapro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility	We will measure the percentage of screened eligible patients who agree to be randomized. Participants were assessed for this Outcome Measure before randomization.This would occur at the first study visit (screening).	This would occur at the first study visit (screening).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of Acute Tryptophan Depletion on Mood	We will examine differences in scores on the the HAMD-28 before and after acute tryptophan depletion. Changes in these parameters will be compared between placebo responders and drug responders using unpaired two-tailed t-tests. The HAMD-28 measures depression severity, and has a minimum value of 0 and a maximum value of 81 units on a scale, where higher scores indicate more severe depression. A negative change value refers to a decrease in HAM D score.	Baseline, Visit 10 (after 9 weeks in study)
Effects of Acute Tryptophan Depletion on Mood	We will examine differences in scores on the the HAMD-28 before and after acute tryptophan depletion. Changes in these parameters will be compared between placebo responders and drug responders using unpaired two-tailed t-tests. The HAMD-28 measures depression severity, and has a minimum value of 0 and a maximum value of 81 units on a scale, where higher scores indicate more severe depression. A negative change value refers to a decrease in HAM D score.	Baseline, Visit 5 (4 weeks into study)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of Acute Tryptophan Depletion on Serotonin Binding	We will examine percentage changes in serotonin binding potential before and after acute tryptophan depletion within each region of interest. We will examine differences in serotonin binding potential between placebo responders and drug responders using a paired two-tailed t-test. Data were not collected	Visit 5 (after 4 weeks in study) or Visit 10 (after 9 weeks in study)

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Cristina Cusin, M.D., Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2012
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: January 16, 2013
• First Submitted That Met QC Criteria: February 6, 2013
• First Posted (Estimate): February 8, 2013

Study Record Updates

• Last Update Posted (Actual): May 16, 2017
• Last Update Submitted That Met QC Criteria: April 18, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Citalopram
• Other Study ID Numbers: 2012P001241

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO