Antidepressant Discontinuation in Treatment Resistant Depression

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.

Study Overview

• Status: Recruiting
• Conditions: Treatment Resistant Depression
• Intervention / Treatment: Other: Discontinuation of serotonergic antidepressants; Other: Continuation of serotonergic medications

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lucas Miozza; Phone Number: 502-588-0678; Email: lgmioz01@louisville.edu

Study Locations

• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • University of Louisville, Department of Psychiatry and Behavioral Sciences
      • Principal Investigator: Rif S. El-Mallakh, MD
      • Sub-Investigator: Ziad A. Ali, MD
      • Contact: Lucas Miozza; Phone Number: 502-588-0678; Email: lgmioz01@louisville.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From baseline and every visit [every 4 weeks] to the end of the study. [6 months]
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).	End of study [6 months].

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From baseline and every visit [every 4 weeks] to the end of the study. [6 months]
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.	From baseline and every visit [every 4 weeks] to the end of the study. [6 months]

Collaborators and Investigators

• Sponsor: University of Louisville
• Investigators: Principal Investigator: Rifaat S. El-Mallakh, MD, University of Louisville, Department of Psychiatry and Behavioral Sciences

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2019
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: December 18, 2018
• First Submitted That Met QC Criteria: December 23, 2018
• First Posted (Actual): December 26, 2018

Study Record Updates

• Last Update Posted (Actual): August 18, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: treatment resistant depression; serotonergic antidepressants; short form of serotonin transporter
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Psychotropic Drugs; Antidepressive Agents
• Other Study ID Numbers: 18.1351

Drug and device information, study documents

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