DepressionNCT00456014
Pre-Treatment Positron Emission Topography Scanning for Increasing Success in Antidepressant Treatment
A study testing Escitalopram and Desipramine in people with Depression, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
This study will use pre-treatment positron emission topography and functional magnetic resonance imaging scans of the brain to predict the most effective antidepressant treatment for people with major depressive disorder. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Depression
- What is being tested?
- Escitalopram and Desipramine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2006to May 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of current major depressive disorder
- Currently depressed
- Subjects must be generally healthy with no significant medical problems, anemia/blood loss, or cardiac abnormalities
- Likely to tolerate medication washout
- Capacity to provide informed consent
- Off of anti-coagulant/anti-platelet treatment for 10 days
- Willing to travel to Brookhaven for PET scanning
Who cannot join
- Current abuse of or dependence on alcohol or another substance (>6 months remission okay)
- History of other major psychiatric disorders such as bipolar, schizophrenia, schizoaffective; anorexia or bulimia in past year
- First degree family history of schizophrenia if subject is under 33
- Unable/unwilling to discontinue all psychotropic medication that affects the serotonin system
- Pregnant, breastfeeding, or planning to become pregnant during the study
- A medical contraindication to antidepressants
Show all 15Show fewer
- Dementia
- Prior head trauma with evidence of cognitive impairment
- Well-documented failure of two or more SSRI AND tricyclic antidepressant (TCA) trials of adequate dose and duration
- Metal implants, pacemaker, metal protheses or orthodontic appliance, the presence of shrapnel
- Current past, present, or anticipated exposure to radiation
- Actively suicidal
- Lifetime history of glaucoma
- Lack of response to >2 trials of antidepressant monotherapy of adequate dose and duration
- Claustrophobia
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University/New York State Psychiatric Institute
New York, New York, 10032
About this study
Official title: Biological Predictors of Response to Antidepressants
This study will use pre-treatment positron emission topography and functional magnetic resonance imaging scans of the brain to predict the most effective antidepressant treatment for people with major depressive disorder.
Read the detailed description
Major depressive disorder (MDD) is characterized by a combination of symptoms that can interfere with a person's ability to work, study, sleep, eat, and enjoy activities that were once pleasurable. Studies have shown that as little as 50% to 60% of individuals with MDD may respond to the first antidepressant medication prescribed. Currently psychiatrists lack tools that allow them to select the treatment plan that is most likely to benefit a particular individual. Some of the chemical abnormalities in the brains of people with MDD are detectable on positron emission topography (PET) scans. There are distinct differences in the PET scans of people with MDD who respond to treatment with a selective serotonin reuptake inhibitor (SSRI), people with MDD who do not respond to SSRI treatment, and people who do not have MDD. This study will use pretreatment PET and functional magnetic resonance imaging (fMRI) scans of the brain to predict which antidepressants will be most effective in people with MDD. This may help to reduce the trial and error currently associated with antidepressant treatment.
We will perform pretreatment PET scans to quantify serotonin transporter (5-HTT) and serotonin 1A (5-HT1A) receptor in patients with major depressive disorder (MDD). All patients will then receive a standardized treatment protocol with a selective serotonin reuptake inhibitor (SSRI), escitalopram. If the patient does not remit, he or she will receive a selective norepinephrine reuptake inhibitor (NRI), desipramine. We hypothesize those patients with high pre and postsynaptic 5-HT1A BP and low 5-HTT BP in specific brain regions will not remit to a SSRI and will remit to a selective NRI. Finally, we will generate a predictive model of remission based on brain imaging outcome measures. Our overall goal is to reduce the trial and error associated with antidepressant treatment by using data from pre-treatment quantification of 5-HT1A receptors and 5-HTT to guide antidepressant treatment selection.
- Conditions
- Depression
- Being tested
- Escitalopram, Desipramine
- Keywords
- Major Depression, Antidepressants
- Medical subject headings
- Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EscitalopramDrug
Also called Lexapro
Escitalopram will be administered at a dose of 10 mg daily for 4 weeks. If participants have not achieved response (greater than 50 % improvement in Hamilton Depression Rating Scale) by 4 weeks, the dose will be increased to 20 mg. Remission status is determined after an 8-week trial.
DesipramineDrug
Also called Norpramin
Subsequent to escitalopram trial, non-remitters will be offered pharmacotherapy with desipramine. Desipramine will be initiated at a dose of 50 mg and titrated according to a treatment manual, with monitoring of therapeutic blood levels. Remission status is determined after an 8-week trial.
| Study group | Role | What they receive |
|---|---|---|
| 1 - SSRI | Experimental | Participants will receive standardized pharmacotherapy with the SSRI escitalopram over 8 weeks. Non-remitters after 8 weeks will be offered standardized pharmacotherapy with desipramine Receives: Drug: Escitalopram; Drug: Desipramine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Remission of Depressive Symptoms
Remission in this study is defined as both a ≥50% decrease in the 24-item Hamilton Depression Rating Scale (HDRS) Score and a final 24-item HDRS score <10. Remission of depressive symptoms was calculated for the 28 completers of the SSRI phase.
Measured: Measured at Week 8
Secondary outcomes (2)
Remission of Depressive Symptoms - Tricyclic Phase
Participants who did not achieve remission during the SSRI phase advanced to the tricyclic phase of the study. Participants were treated with either desipramine or nortriptyline. Seven participants started the tricyclic phase. Four completed the tricyclic phase. The completers (n=4) were analyzed for remission status.
Measured: Measured over 8 weeks
Improvement in Scores on the Hamilton Depression Rating Scale - SSRI Phase
Mean % improvement from baseline to end of treatment trial using the 24-item Hamilton Depression Rating Scale. Percent improvement of depressive symptoms was calculated for the 28 completers of the SSRI phase. The higher the score on the 24-item HDRS, the greater the depression severity. Minimum score on the scale is 0, and maximum score is 74. Subscales are not used for this analysis.
Measured: Measured at Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2007 (estimated)
- Study startSep 2006
- Primary completionMay 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Jeffrey Miller, New York State Psychiatric Institute
- Investigators
- Ramin V. Parsey, MD, PhD, Principal investigator, Columbia UniversityJeffrey M Miller, MD, Principal investigator, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00456014
- Sponsor's protocol ID
- #6351R (formerly 5206)
- Other IDs
- R01MH074813, DATR A3-NSS
- Status last verified
- Mar 2019
- First submitted
- 2 Apr 2007
- Last updated
- 19 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Miller JM, Hesselgrave N, Ogden RT, Zanderigo F, Oquendo MA, Mann JJ, Parsey RV. Brain serotonin 1A receptor binding as a predictor of treatment outcome in major depressive disorder. Biol Psychiatry. 2013 Nov 15;74(10):760-7. doi: 10.1016/j.biopsych.2013.03.021. Epub 2013 May 9.
PubMed 23664414
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biological Predictors of Response to Antidepressants
- ClinicalTrials.gov ID
- NCT00456014
- Acronym / sponsor ID
- #6351R (formerly 5206)
- Conditions
- Depression
- Keywords
- Major Depression, Antidepressants
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Sep 2006
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 4 Apr 2007 (estimated)
- Results
- Posted 14 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will use pre-treatment positron emission topography and functional magnetic resonance imaging scans of the brain to predict the most effective antidepressant treatment for people with major depressive disorder.
Detailed description
Major depressive disorder (MDD) is characterized by a combination of symptoms that can interfere with a person's ability to work, study, sleep, eat, and enjoy activities that were once pleasurable. Studies have shown that as little as 50% to 60% of individuals with MDD may respond to the first antidepressant medication prescribed. Currently psychiatrists lack tools that allow them to select the treatment plan that is most likely to benefit a particular individual. Some of the chemical abnormalities in the brains of people with MDD are detectable on positron emission topography (PET) scans. There are distinct differences in the PET scans of people with MDD who respond to treatment with a selective serotonin reuptake inhibitor (SSRI), people with MDD who do not respond to SSRI treatment, and people who do not have MDD. This study will use pretreatment PET and functional magnetic resonance imaging (fMRI) scans of the brain to predict which antidepressants will be most effective in people with MDD. This may help to reduce the trial and error currently associated with antidepressant treatment.
We will perform pretreatment PET scans to quantify serotonin transporter (5-HTT) and serotonin 1A (5-HT1A) receptor in patients with major depressive disorder (MDD). All patients will then receive a standardized treatment protocol with a selective serotonin reuptake inhibitor (SSRI), escitalopram. If the patient does not remit, he or she will receive a selective norepinephrine reuptake inhibitor (NRI), desipramine. We hypothesize those patients with high pre and postsynaptic 5-HT1A BP and low 5-HTT BP in specific brain regions will not remit to a SSRI and will remit to a selective NRI. Finally, we will generate a predictive model of remission based on brain imaging outcome measures. Our overall goal is to reduce the trial and error associated with antidepressant treatment by using data from pre-treatment quantification of 5-HT1A receptors and 5-HTT to guide antidepressant treatment selection.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 - SSRI | Experimental | Drug: Escitalopram, Drug: DesipramineParticipants will receive standardized pharmacotherapy with the SSRI escitalopram over 8 weeks. Non-remitters after 8 weeks will be offered standardized pharmacotherapy with desipramine |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Diagnosis of current major depressive disorder
- Currently depressed
- Subjects must be generally healthy with no significant medical problems, anemia/blood loss, or cardiac abnormalities
- Likely to tolerate medication washout
- Capacity to provide informed consent
Key exclusion criteria (15 listed)
- Current abuse of or dependence on alcohol or another substance (>6 months remission okay)
- History of other major psychiatric disorders such as bipolar, schizophrenia, schizoaffective; anorexia or bulimia in past year
- First degree family history of schizophrenia if subject is under 33
- Unable/unwilling to discontinue all psychotropic medication that affects the serotonin system
- Pregnant, breastfeeding, or planning to become pregnant during 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 |
|---|---|---|
| EscitalopramAlso: LexaproEscitalopram will be administered at a dose of 10 mg daily for 4 weeks. If participants have not achieved response (greater than 50 % improvement in Hamilton Depression Rating Scale) by 4 weeks, the dose will be increased to 20 mg. Remission status is determined after an 8-week trial. | Drug | 1 - SSRI |
| DesipramineAlso: NorpraminSubsequent to escitalopram trial, non-remitters will be offered pharmacotherapy with desipramine. Desipramine will be initiated at a dose of 50 mg and titrated according to a treatment manual, with monitoring of therapeutic blood levels. Remission status is determined after an 8-week trial. | Drug | 1 - SSRI |
Primary outcome
Remission of Depressive Symptoms
Time frame: Measured at Week 8
Remission in this study is defined as both a ≥50% decrease in the 24-item Hamilton Depression Rating Scale (HDRS) Score and a final 24-item HDRS score <10. Remission of depressive symptoms was calculated for the 28 completers of the SSRI phase.
2 secondary outcomes
Remission of Depressive Symptoms - Tricyclic Phase
Time frame: Measured over 8 weeks
Improvement in Scores on the Hamilton Depression Rating Scale - SSRI Phase
Time frame: Measured at Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23664414Miller JM, Hesselgrave N, Ogden RT, Zanderigo F, Oquendo MA, Mann JJ, Parsey RV. Brain serotonin 1A receptor binding as a predictor of treatment outcome in major depressive disorder. Biol Psychiatry. 2013 Nov 15;74(10):760-7. doi: 10.1016/j.biopsych.2013.03.021. Epub 2013 May 9.
- Individual participant dataSharing planned: No
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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.
Ramin V. Parsey, MD, PhD principal investigator
Columbia University
Jeffrey M Miller, MD principal investigator
New York State Psychiatric Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Escitalopram and Desipramine in people with Depression, run by New York State Psychiatric Institute 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 7 inclusion and 15 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: finished, as of the sponsor's last update on 19 Mar 2019. 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?
Yes. Results are posted in the registry (first posted 14 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Remission of Depressive Symptoms (time frame: Measured at Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00456014, which also lists 1 linked publication.
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 19 Mar 2019.