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Antidepressant Discontinuation in Treatment Resistant Depression

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ClinicalTrials.gov Identifier: NCT03786614
Recruitment Status : Not yet recruiting
First Posted : December 25, 2018
Last Update Posted : December 25, 2018
Sponsor:
Information provided by (Responsible Party):
Rifaat S. El-Mallakh, University of Louisville

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.

Condition or disease Intervention/treatment Phase
Treatment Resistant Depression Other: Discontinuation of serotonergic antidepressants Other: Continuation of serotonergic medications Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (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
Primary Purpose: Treatment
Official Title: Antidepressant Discontinuation in Treatment Resistant Depression
Estimated Study Start Date : February 2019
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antidepressants

Arm Intervention/treatment
Active Comparator: Discontinuation arm
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.
Other: Discontinuation of serotonergic antidepressants
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.

Active Comparator: Continuation arm
This group will continue taking serotonergic antidepressants which is the standard care of treatment.
Other: Continuation of serotonergic medications
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 Measures :
  1. Comparing the difference of response as measured by the Montgomery-Åsberg Depression Rating Scale [MADRS] between both arms. [ Time Frame: From baseline and every visit [every 4 weeks] to the end of the study. [6 months] ]
    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.

  2. 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. [ Time Frame: End of study [6 months]. ]
    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 :
  1. Evaluating changes in levels of anxiety as measured by the Hamilton Anxiety Rating Scale [HAM-A] between both arms. [ Time Frame: From baseline and every visit [every 4 weeks] to the end of the study. [6 months] ]
    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.

  2. Evaluating the difference of response as measured by the Columbia Suicide Severity Rating Scale [C-SSRS] between both arms. [ Time Frame: From baseline and every visit [every 4 weeks] to the end of the study. [6 months] ]
    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.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03786614


Contacts
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Contact: Sharon Nuss 502-588-0678 sharon.nuss@louisville.edu

Locations
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United States, Kentucky
University of Louisville, Department of Psychiatry and Behavioral Sciences Not yet recruiting
Louisville, Kentucky, United States, 40202
Contact: Sharon Nuss    502-588-0678    sharon.nuss@louisville.edu   
Principal Investigator: Rif S. El-Mallakh, MD         
Sub-Investigator: Ziad A. Ali, MD         
Sponsors and Collaborators
University of Louisville
Investigators
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Principal Investigator: Rifaat S. El-Mallakh, MD University of Louisville, Department of Psychiatry and Behavioral Sciences

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Responsible Party: Rifaat S. El-Mallakh, Professor, University of Louisville
ClinicalTrials.gov Identifier: NCT03786614     History of Changes
Other Study ID Numbers: TRD2018
First Posted: December 25, 2018    Key Record Dates
Last Update Posted: December 25, 2018
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rifaat S. El-Mallakh, University of Louisville:
treatment resistant depression
serotonergic antidepressants
short form of serotonin transporter
Additional relevant MeSH terms:
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Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders
Antidepressive Agents
Serotonin
Psychotropic Drugs
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs