Treatment Resistant DepressionNCT03786614
Antidepressant Discontinuation in Treatment Resistant Depression
A study testing Discontinuation of serotonergic antidepressants and Continuation of serotonergic medications in people with Treatment Resistant Depression, run by University of Louisville at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Discontinuation of serotonergic antidepressants and Continuation of serotonergic medications
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jun 2019to Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
University of Louisville, Department of Psychiatry and Behavioral Sciences
Louisville, Kentucky, 40202
Lucas Miozza, 502-588-0678, lgmioz01@louisville.edu
Rif S. El-Mallakh, MD
About this study
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
- Being tested
- Discontinuation of serotonergic antidepressants, Continuation of serotonergic medications
- Keywords
- treatment resistant depression, serotonergic antidepressants, short form of serotonin transporter
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Discontinuation of serotonergic antidepressantsOther
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.
Continuation of serotonergic medicationsOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Discontinuation of serotonergic antidepressants |
| Continuation arm | Active comparator | This group will continue taking serotonergic antidepressants which is the standard care of treatment. Receives: Other: Continuation of serotonergic medications |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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.
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.
Measured: 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.
Measured: From baseline and every visit [every 4 weeks] to the end of the study. [6 months]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2018
- Study start20 Jun 2019
- Primary completionDec 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- More trials run by University of LouisvilleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Louisville
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rifaat S. El-Mallakh, University of Louisville
- Investigators
- Rifaat S. El-Mallakh, MD, Principal investigator, University of Louisville, Department of Psychiatry and Behavioral Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03786614
- Sponsor's protocol ID
- 18.1351
- Status last verified
- Aug 2023
- First submitted
- 18 Dec 2018
- Last updated
- 18 Aug 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antidepressant Discontinuation in Treatment Resistant Depression
- ClinicalTrials.gov ID
- NCT03786614
- Acronym / sponsor ID
- 18.1351
- Conditions
- Treatment Resistant Depression
- Keywords
- treatment resistant depression, serotonergic antidepressants, short form of serotonin transporter
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of LouisvilleUniversity, hospital or other
- Study start
- 20 Jun 2019 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 26 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Discontinuation arm | Active comparator | Other: Discontinuation of serotonergic antidepressantsThis 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. |
| Continuation arm | Active comparator | Other: Continuation of serotonergic medicationsThis group will continue taking serotonergic antidepressants which is the standard care of treatment. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Discontinuation of serotonergic antidepressantsDiscontinuation 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. | Other | Discontinuation arm |
| Continuation of serotonergic medicationsContinuation of serotonergic medications which is the standard care of treatment. Additionally, subjects will have access to other treatment measures of treating treatment resistant depression. | Other | Continuation arm |
Primary outcome
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.
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).
2 secondary outcomes
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]
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]
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rifaat S. El-Mallakh, MD principal investigator
University of Louisville, Department of Psychiatry and Behavioral Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Discontinuation of serotonergic antidepressants and Continuation of serotonergic medications in people with Treatment Resistant Depression, run by University of Louisville at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lucas Miozza (502-588-0678, lgmioz01@louisville.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2023; AzTrials last refreshed its copy on 6 Nov 2026.