Major Depressive Disorder
Conditions
Brief summary
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.
Interventions
DRUGPlacebo
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility | This would occur at the first study visit (screening). | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effects of Acute Tryptophan Depletion on Mood | Baseline, Visit 10 (after 9 weeks in study) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Effects of Acute Tryptophan Depletion on Serotonin Binding | Visit 5 (after 4 weeks in study) or Visit 10 (after 9 weeks in study) | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo After a screening visit, the patient will undergo a baseline assessment and will be randomized to escitalopram 10mg or placebo.
Placebo | 15 |
| Escitalopram 10mg After a screening visit, the patient will undergo a baseline assessment and will be randomized to escitalopram 10mg or placebo.
Escitalopram 10mg | 5 |
| Total | 20 |
Baseline characteristics
| Characteristic | Placebo | Escitalopram 10mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 5 Participants | 20 Participants |
| Age, Continuous | 32.6 Years STANDARD_DEVIATION 14.1 | 33 Years STANDARD_DEVIATION 11.64 | 32.7 Years STANDARD_DEVIATION 13.23 |
| Region of Enrollment United States | 15 participants | 5 participants | 20 participants |
| Sex: Female, Male Female | 7 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Male | 8 Participants | 2 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 5 |
| other Total, other adverse events | 12 / 15 | 1 / 5 |
| serious Total, serious adverse events | 4 / 15 | 2 / 5 |
Outcome results
Primary
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).
Time frame: This would occur at the first study visit (screening).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eligible Patients | Feasibility | 95.2 percent of eligible patients |
Secondary
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.
Time frame: Baseline, Visit 10 (after 9 weeks in study)
Population: Participants assigned to take either active drug or placebo who did not respond by the end of phase 1 (Week 5 of study treatment) continued onto phase 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eligible Patients | Effects of Acute Tryptophan Depletion on Mood | -6.0 units on a scale | Standard Deviation 6.4 |
| Phase 2 Active | Effects of Acute Tryptophan Depletion on Mood | -13.0 units on a scale | Standard Deviation 12.1 |
Secondary
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.
Time frame: Baseline, Visit 5 (4 weeks into study)
Population: Patients who were randomized to take placebo or active drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eligible Patients | Effects of Acute Tryptophan Depletion on Mood | -6.4 units on a scale | Standard Deviation 8.5 |
| Phase 2 Active | Effects of Acute Tryptophan Depletion on Mood | -8.8 units on a scale | Standard Deviation 6.3 |
Other Pre-specified
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
Time frame: Visit 5 (after 4 weeks in study) or Visit 10 (after 9 weeks in study)
Population: Data were not collected