Antidepressant Discontinuation in Treatment Resistant Depression

NCT03786614 | Unknown

• 1 other identifier: 18.1351
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Treatment Resistant Depression

Keywords

treatment resistant depression; serotonergic antidepressants; short form of serotonin transporter

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Evaluating changes in levels of anxiety as measured by the Hamilton Anxiety Rating Scale [HAM-A] between both arms.

  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.

  From baseline and every visit [every 4 weeks] to the end of the study. [6 months]

Study Arms (2)

Discontinuation arm

ACTIVE COMPARATOR

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

Continuation arm

ACTIVE COMPARATOR

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

Other: Continuation of serotonergic medications

Interventions

Discontinuation of serotonergic antidepressants OTHER

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.

Discontinuation arm

Continuation of serotonergic medications OTHER

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.

Continuation arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Louisville: lead

Study Sites (1)

University of Louisville, Department of Psychiatry and Behavioral Sciences

Louisville, Kentucky, 40202, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Rifaat S. El-Mallakh, MD

  University of Louisville, Department of Psychiatry and Behavioral Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lucas Miozza

CONTACT

502-588-0678; lgmioz01@louisville.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The person performing the data collection (rater) will be blind to the randomization of the patient for the entire duration of the study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 18, 2018
• First Posted: December 26, 2018
• Study Start: June 20, 2019
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: August 18, 2023

Record last verified: 2023-08

Locations

US (1)