Structural and Functional Connectivity of Brainstem Monoamine Pathways in Treatment Resistant Depression (MAOI)

Study TRD subjects' resistance to at least 2 different antidepressants, we hypothesize that because of their significant depression and treatment resistant status they are most likely to exhibit BSMN pathway abnormalities.

Study Overview

• Status: Completed
• Conditions: Treatment Resistant Depression
• Intervention / Treatment: Drug: Monoamine Oxidase Inhibitor (MAOI)

Detailed Description

Potential subjects will be identified during clinical visits. If a patient qualifies to participate in the study they will have to stop any antidepressants that they are taking to prepare for the use of MAOIs. After a two week washout period, subjects will have an fMRI and will be started on a MAOI. They will then be followed up for 8 weeks, which is routine and considered standard care.

• Study Type: Observational
• Enrollment (Actual): 11

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Treatment Resistant Depression and Healthy Controls

Description

Inclusion Criteria - TRD:

1. age: 18 - 65 yrs.;
2. satisfy criteria for DSM-IV major depressive disorder (MDD);
3. 17-item Hamilton Depression Rating Scale (17-item HDRS) score > 18;
4. treatment resistance depression as defined as report of inadequate response (patient report of minimal improvement or nonresponse) despite past treatment with at least 2 different classes of antidepressants acting on the 5-HT and/or DA monoamine systems(except MAOIs) (as determined with the Antidepressant Treatment History Form (ATHF)20 with score of >3 on each of the items and verified by medical records if available);
5. able to give informed consent;
6. no use of alcohol in the past 1 week and negative urine toxicology screen;
7. MAOI treatment indicated as assessed by an independent psychiatrist not affiliated with the study;
8. voluntary consent to treatment with an MAOI after reviewing all other options and agree to follow safeguards and precautions during treatment.

Inclusion criteria for healthy subjects

1. ages 18-65 years and ability to give voluntary informed consent;
2. no history of psychiatric illness or substance abuse or dependence;
3. no significant family history of psychiatric or neurological illness;
4. not currently taking any prescription or centrally acting medications; no use of alcohol in the past 1 week;
5. and no serious medical or neurological illness.

Exclusion Criteria - TRD:

1. schizophrenia, schizoaffective or primary anxiety disorder;
2. serious medical or neurological illness;
3. history of significant head injury;
4. on fluoxetine treatment;
5. on lithium or have received ECT or rTMS in the last 3 months to avoid long-term effects of such medications;
6. substance or alcohol dependence in the past 6 months or substance abuse in the past 3 months;
7. unable to give informed consent.

Exclusion criteria for both groups:

1. pregnant or breast-feeding;
2. metallic implants or other contraindication to MRI.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Treatment Resistant Depression; Screened for eligibility using several psychiatric assessments. If qualifies to participate in the study, will have to stop any antidepressants that they are taking to prepare for the use of Monoamine Oxidase Inhibitor(MAOI). After a two week washout period, subjects will have an fMRI and will be started on a MAOI. Then be followed for 8 weeks, part of routine care.	Drug: Monoamine Oxidase Inhibitor (MAOI); Monoamine Oxidase Inhibitor; Other Names: Monoamine Oxidase Inhibitor
Healthy Control; Screen for eligibility, then MRI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brainstem Structural Connectivity (Sc)	Localize BSMN and measure pathway Sc using diffusion imaging to differentiate between TRD and HC. BSMN can be localized using diffusion imaging, and pathways projecting from BSMN to known targets can be identified. Methods have been developed to localize these nuclei via a combination of diffusion imaging and anatomic imaging. We will identify these nuclei and track their projections to known targets, giving rise to the VTA-NAcc, VTA-AMYG, RN-AM and RN-sgACC pathways. Probabilistic fiber tracking between these nodes will be used to determine a measure of pathway strength.	2 years
Brainstem Functional Connectivity (Fc)	Measure BSMN pathway Fc to differentiate between TRD and HC. BSMN associated with different neuromodulators, e.g. the VTA and RN, will be associated with distinct functional networks which will be abnormal in TRD compared to HCs.	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
17-item Hamilton Depression Rating Scale	Compare baseline and end of study Hamilton depression Rating scale and imaging correlations.	2 years

Collaborators and Investigators

• Sponsor: Kathryn O'Connor

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): November 1, 2020
• Study Completion (Actual): May 1, 2021

Study Registration Dates

• First Submitted: March 1, 2017
• First Submitted That Met QC Criteria: April 10, 2017
• First Posted (Actual): April 12, 2017

Study Record Updates

• Last Update Posted (Actual): June 18, 2021
• Last Update Submitted That Met QC Criteria: June 15, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Treatment Resistant Depression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Monoamine Oxidase Inhibitors
• Other Study ID Numbers: 15-1372

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No