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Antidepressant Discontinuation in Treatment Resistant Depression

Primary Purpose

Treatment Resistant Depression

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Discontinuation of serotonergic antidepressants
Continuation of serotonergic medications
Sponsored by
University of Louisville
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Treatment Resistant Depression focused on measuring treatment resistant depression, serotonergic antidepressants, short form of serotonin transporter

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects must be a man or woman 18 to 70 years of age, inclusive.
  • Subject must meet criteria for a major depressive disorder as confirmed by the Mini International Neuropsychiatric Interview [MINI].
  • Subjects must have a current Treatment-Resistant Depression as defined below.
  • Subjects must have been taking serotonergic antidepressants (serotonin reuptake inhibitor or monoamine oxidase inhibitor) for at least 2 years but not more than 4 years, and have failed 2 previous medication trial for the current episode. Current Montgomery-Åsberg Depression Rating Scale [MADRS] score must be equal to or more than 25.
  • Subject must be medically stable.
  • Female subjects must have a negative urine pregnancy test at screening, and agree to avoid pregnancy during the study.
  • Each subject must sign an informed consent form indicating that he/she understands the purpose of the study and the procedures required and are willing to participate in the study.
  • Subject must be able to participate in symptom measurement.

Exclusion Criteria:

  • Subject has a current Diagnostic and Statistical Manual of Mental Disorders-5 [DSM-5] diagnosis of bipolar disorder or has a positive screening for bipolar disorder by Mini International Neuropsychiatric Interview [MINI] or Mood Disorder Questionnaire [MDQ].
  • Subject has a current DSM-5 diagnosis of schizophrenia, schizoaffective disorder, autistic disorder, or intellectual disability.
  • Subject has a substance use disorder (except for nicotine or cannabis) within 3 months prior to screening or has a positive drug screen test for any recreational drugs at the time of screening with the exception of Cannabis.
  • Subject has evidence of any clinically significant, unstable medical problems that may create a safety risk for a subject, interfere with study participation, or make results difficult to interpret.
  • Subject is at imminent risk of suicide according to the investigator's clinical judgment and/or a Columbia-Suicide Severity Rating Scale (C-SSRS) 3 or more at any time in the study.
  • Subject is a woman who is pregnant, breast-feeding or planning to become pregnant while enrolled in the study.
  • Subject has any condition (according to the investigator) for which participation will not be the best interest for the subject or it can prevent, limit or confound the protocol-specified assessments.

Sites / Locations

  • University of Louisville, Department of Psychiatry and Behavioral SciencesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Discontinuation arm

Continuation arm

Arm Description

This group will be discontinued from serotonergic antidepressants and shifting them to other categories of antidepressants, i.e., medications that work through dopamine or nor-epinephrine, or by reducing the serotonin signal rather than increasing synaptic serotonin, as might be accomplished with low dose, sub-anti-psychotic doses of some second-generation anti-psychotics.

This group will continue taking serotonergic antidepressants which is the standard care of treatment.

Outcomes

Primary Outcome Measures

Comparing the difference of response as measured by the Montgomery-Åsberg Depression Rating Scale [MADRS] between both arms.
The MADRS is a psychiatric scale to assess the depressive symptoms from the patient's prospective. The final score ranges from 0 to 60 with 0 indicating no depression and higher scores indicating greater depression. The final scores will be evaluated with a non-paired, two-tailed t-test.
Comparing the difference of response as measured by the Montgomery-Åsberg Depression Rating Scale [MADRS] between subjects with low expressing alleles and high expressing alleles of the serotonin gene transporter.
Genetic testing for the serotonin transporter gene will be done for every patient in the study. All subjects with homozygous and heterozygous low expression alleles will be combined as one group, and all high expression subjects will be the other group. One-way ANOVAs will be conducted for each genotype group, with genotype group as the independent variable (IV) and MADRS scores as the dependent variables (DV).

Secondary Outcome Measures

Evaluating changes in levels of anxiety as measured by the Hamilton Anxiety Rating Scale [HAM-A] between both arms.
The HAM-A will be collected to assess changes in anxiety levels from the patient's prospective. It ranges from 0 to 56 with greater scores indicating more anxiety. The final scores will be evaluated with a non-paired, two-tailed t-test.
Evaluating the difference of response as measured by the Columbia Suicide Severity Rating Scale [C-SSRS] between both arms.
The C-SSRS is a psychiatric scale to assess suicidality. It ranges from 0 to 5 with 0 indicating no suicidal ideas and higher scores indicating greater suicidal ideas. The final scores will be evaluated with a non-paired, two-tailed t-test.

Full Information

First Posted
December 18, 2018
Last Updated
August 16, 2023
Sponsor
University of Louisville
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1. Study Identification

Unique Protocol Identification Number
NCT03786614
Brief Title
Antidepressant Discontinuation in Treatment Resistant Depression
Official Title
Antidepressant Discontinuation in Treatment Resistant Depression
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 20, 2019 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Louisville

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The purpose of this study is to compare the effects on depressive symptoms of subjects who discontinue serotonergic antidepressants (a certain type of antidepressant, such as Prozac, that works on serotonin receptors in the brain) with the effects on depressive symptoms of subjects who continue to take serotonergic antidepressants. During this study, subjects will also be presented with the opportunity to undergo genetic testing for the serotonin gene transporter which has a short or long form. This is being done because it has been demonstrated that genetic testing improves outcome while treating treatment-resistant depression.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Treatment Resistant Depression
Keywords
treatment resistant depression, serotonergic antidepressants, short form of serotonin transporter

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Masking Description
The person performing the data collection (rater) will be blind to the randomization of the patient for the entire duration of the study
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Discontinuation arm
Arm Type
Active Comparator
Arm Description
This group will be discontinued from serotonergic antidepressants and shifting them to other categories of antidepressants, i.e., medications that work through dopamine or nor-epinephrine, or by reducing the serotonin signal rather than increasing synaptic serotonin, as might be accomplished with low dose, sub-anti-psychotic doses of some second-generation anti-psychotics.
Arm Title
Continuation arm
Arm Type
Active Comparator
Arm Description
This group will continue taking serotonergic antidepressants which is the standard care of treatment.
Intervention Type
Other
Intervention Name(s)
Discontinuation of serotonergic antidepressants
Intervention Description
Discontinuation of serotonergic antidepressants and possibly shift to other antidepressant categories that were proven to be effective in treating depression such as pramipexole, bupropion, quetiapine, lurasidone, brexpipazole. Additionally, subjects will have access to other treatment measures of treating treatment resistant depression.
Intervention Type
Other
Intervention Name(s)
Continuation of serotonergic medications
Intervention Description
Continuation of serotonergic medications which is the standard care of treatment. Additionally, subjects will have access to other treatment measures of treating treatment resistant depression.
Primary Outcome Measure Information:
Title
Comparing the difference of response as measured by the Montgomery-Åsberg Depression Rating Scale [MADRS] between both arms.
Description
The MADRS is a psychiatric scale to assess the depressive symptoms from the patient's prospective. The final score ranges from 0 to 60 with 0 indicating no depression and higher scores indicating greater depression. The final scores will be evaluated with a non-paired, two-tailed t-test.
Time Frame
From baseline and every visit [every 4 weeks] to the end of the study. [6 months]
Title
Comparing the difference of response as measured by the Montgomery-Åsberg Depression Rating Scale [MADRS] between subjects with low expressing alleles and high expressing alleles of the serotonin gene transporter.
Description
Genetic testing for the serotonin transporter gene will be done for every patient in the study. All subjects with homozygous and heterozygous low expression alleles will be combined as one group, and all high expression subjects will be the other group. One-way ANOVAs will be conducted for each genotype group, with genotype group as the independent variable (IV) and MADRS scores as the dependent variables (DV).
Time Frame
End of study [6 months].
Secondary Outcome Measure Information:
Title
Evaluating changes in levels of anxiety as measured by the Hamilton Anxiety Rating Scale [HAM-A] between both arms.
Description
The HAM-A will be collected to assess changes in anxiety levels from the patient's prospective. It ranges from 0 to 56 with greater scores indicating more anxiety. The final scores will be evaluated with a non-paired, two-tailed t-test.
Time Frame
From baseline and every visit [every 4 weeks] to the end of the study. [6 months]
Title
Evaluating the difference of response as measured by the Columbia Suicide Severity Rating Scale [C-SSRS] between both arms.
Description
The C-SSRS is a psychiatric scale to assess suicidality. It ranges from 0 to 5 with 0 indicating no suicidal ideas and higher scores indicating greater suicidal ideas. The final scores will be evaluated with a non-paired, two-tailed t-test.
Time Frame
From baseline and every visit [every 4 weeks] to the end of the study. [6 months]

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must be a man or woman 18 to 70 years of age, inclusive. Subject must meet criteria for a major depressive disorder as confirmed by the Mini International Neuropsychiatric Interview [MINI]. Subjects must have a current Treatment-Resistant Depression as defined below. Subjects must have been taking serotonergic antidepressants (serotonin reuptake inhibitor or monoamine oxidase inhibitor) for at least 2 years but not more than 4 years, and have failed 2 previous medication trial for the current episode. Current Montgomery-Åsberg Depression Rating Scale [MADRS] score must be equal to or more than 25. Subject must be medically stable. Female subjects must have a negative urine pregnancy test at screening, and agree to avoid pregnancy during the study. Each subject must sign an informed consent form indicating that he/she understands the purpose of the study and the procedures required and are willing to participate in the study. Subject must be able to participate in symptom measurement. Exclusion Criteria: Subject has a current Diagnostic and Statistical Manual of Mental Disorders-5 [DSM-5] diagnosis of bipolar disorder or has a positive screening for bipolar disorder by Mini International Neuropsychiatric Interview [MINI] or Mood Disorder Questionnaire [MDQ]. Subject has a current DSM-5 diagnosis of schizophrenia, schizoaffective disorder, autistic disorder, or intellectual disability. Subject has a substance use disorder (except for nicotine or cannabis) within 3 months prior to screening or has a positive drug screen test for any recreational drugs at the time of screening with the exception of Cannabis. Subject has evidence of any clinically significant, unstable medical problems that may create a safety risk for a subject, interfere with study participation, or make results difficult to interpret. Subject is at imminent risk of suicide according to the investigator's clinical judgment and/or a Columbia-Suicide Severity Rating Scale (C-SSRS) 3 or more at any time in the study. Subject is a woman who is pregnant, breast-feeding or planning to become pregnant while enrolled in the study. Subject has any condition (according to the investigator) for which participation will not be the best interest for the subject or it can prevent, limit or confound the protocol-specified assessments.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lucas Miozza
Phone
502-588-0678
Email
lgmioz01@louisville.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rifaat S. El-Mallakh, MD
Organizational Affiliation
University of Louisville, Department of Psychiatry and Behavioral Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Louisville, Department of Psychiatry and Behavioral Sciences
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lucas Miozza
Phone
502-588-0678
Email
lgmioz01@louisville.edu
First Name & Middle Initial & Last Name & Degree
Rif S. El-Mallakh, MD
First Name & Middle Initial & Last Name & Degree
Ziad A. Ali, MD

12. IPD Sharing Statement

Learn more about this trial

Antidepressant Discontinuation in Treatment Resistant Depression

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