Pre-Treatment Positron Emission Topography Scanning for Increasing Success in Antidepressant Treatment

March 11, 2019 updated by: Jeffrey Miller, New York State Psychiatric Institute

Biological Predictors of Response to Antidepressants

This study will use pre-treatment positron emission topography and functional magnetic resonance imaging scans of the brain to predict the most effective antidepressant treatment for people with major depressive disorder.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Major depressive disorder (MDD) is characterized by a combination of symptoms that can interfere with a person's ability to work, study, sleep, eat, and enjoy activities that were once pleasurable. Studies have shown that as little as 50% to 60% of individuals with MDD may respond to the first antidepressant medication prescribed. Currently psychiatrists lack tools that allow them to select the treatment plan that is most likely to benefit a particular individual. Some of the chemical abnormalities in the brains of people with MDD are detectable on positron emission topography (PET) scans. There are distinct differences in the PET scans of people with MDD who respond to treatment with a selective serotonin reuptake inhibitor (SSRI), people with MDD who do not respond to SSRI treatment, and people who do not have MDD. This study will use pretreatment PET and functional magnetic resonance imaging (fMRI) scans of the brain to predict which antidepressants will be most effective in people with MDD. This may help to reduce the trial and error currently associated with antidepressant treatment.

We will perform pretreatment PET scans to quantify serotonin transporter (5-HTT) and serotonin 1A (5-HT1A) receptor in patients with major depressive disorder (MDD). All patients will then receive a standardized treatment protocol with a selective serotonin reuptake inhibitor (SSRI), escitalopram. If the patient does not remit, he or she will receive a selective norepinephrine reuptake inhibitor (NRI), desipramine. We hypothesize those patients with high pre and postsynaptic 5-HT1A BP and low 5-HTT BP in specific brain regions will not remit to a SSRI and will remit to a selective NRI. Finally, we will generate a predictive model of remission based on brain imaging outcome measures. Our overall goal is to reduce the trial and error associated with antidepressant treatment by using data from pre-treatment quantification of 5-HT1A receptors and 5-HTT to guide antidepressant treatment selection.

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • Columbia University/New York State Psychiatric Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of current major depressive disorder
  • Currently depressed
  • Subjects must be generally healthy with no significant medical problems, anemia/blood loss, or cardiac abnormalities
  • Likely to tolerate medication washout
  • Capacity to provide informed consent
  • Off of anti-coagulant/anti-platelet treatment for 10 days
  • Willing to travel to Brookhaven for PET scanning

Exclusion Criteria:

  • Current abuse of or dependence on alcohol or another substance (>6 months remission okay)
  • History of other major psychiatric disorders such as bipolar, schizophrenia, schizoaffective; anorexia or bulimia in past year
  • First degree family history of schizophrenia if subject is under 33
  • Unable/unwilling to discontinue all psychotropic medication that affects the serotonin system
  • Pregnant, breastfeeding, or planning to become pregnant during the study
  • A medical contraindication to antidepressants
  • Dementia
  • Prior head trauma with evidence of cognitive impairment
  • Well-documented failure of two or more SSRI AND tricyclic antidepressant (TCA) trials of adequate dose and duration
  • Metal implants, pacemaker, metal protheses or orthodontic appliance, the presence of shrapnel
  • Current past, present, or anticipated exposure to radiation
  • Actively suicidal
  • Lifetime history of glaucoma
  • Lack of response to >2 trials of antidepressant monotherapy of adequate dose and duration
  • Claustrophobia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1 - SSRI
Participants will receive standardized pharmacotherapy with the SSRI escitalopram over 8 weeks. Non-remitters after 8 weeks will be offered standardized pharmacotherapy with desipramine
Drug: Escitalopram
Escitalopram will be administered at a dose of 10 mg daily for 4 weeks. If participants have not achieved response (greater than 50 % improvement in Hamilton Depression Rating Scale) by 4 weeks, the dose will be increased to 20 mg. Remission status is determined after an 8-week trial.
Other Names:
  • Lexapro
Drug: Desipramine
Subsequent to escitalopram trial, non-remitters will be offered pharmacotherapy with desipramine. Desipramine will be initiated at a dose of 50 mg and titrated according to a treatment manual, with monitoring of therapeutic blood levels. Remission status is determined after an 8-week trial.
Other Names:
  • Norpramin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Remission of Depressive Symptoms
Time Frame: Measured at Week 8
Remission in this study is defined as both a ≥50% decrease in the 24-item Hamilton Depression Rating Scale (HDRS) Score and a final 24-item HDRS score <10. Remission of depressive symptoms was calculated for the 28 completers of the SSRI phase.
Measured at Week 8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Remission of Depressive Symptoms - Tricyclic Phase
Time Frame: Measured over 8 weeks
Participants who did not achieve remission during the SSRI phase advanced to the tricyclic phase of the study. Participants were treated with either desipramine or nortriptyline. Seven participants started the tricyclic phase. Four completed the tricyclic phase. The completers (n=4) were analyzed for remission status.
Measured over 8 weeks
Improvement in Scores on the Hamilton Depression Rating Scale - SSRI Phase
Time Frame: Measured at Week 8
Mean % improvement from baseline to end of treatment trial using the 24-item Hamilton Depression Rating Scale. Percent improvement of depressive symptoms was calculated for the 28 completers of the SSRI phase. The higher the score on the 24-item HDRS, the greater the depression severity. Minimum score on the scale is 0, and maximum score is 74. Subscales are not used for this analysis.
Measured at Week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New York State Psychiatric Institute

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Jeffrey M Miller, MD, New York State Psychiatric Institute
  • Principal Investigator: Ramin V. Parsey, MD, PhD, Columbia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (Actual)

May 1, 2012

Study Completion (Actual)

May 1, 2012

Study Registration Dates

First Submitted

April 2, 2007

First Submitted That Met QC Criteria

April 2, 2007

First Posted (Estimate)

April 4, 2007

Study Record Updates

Last Update Posted (Actual)

March 19, 2019

Last Update Submitted That Met QC Criteria

March 11, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • #6351R (formerly 5206)
  • DATR A3-NSS (Indiana University)
  • R01MH074813 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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