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| ID | Type | Description | Link |
|---|---|---|---|
| R01MH074813 | U.S. NIH Grant/Contract | View source | |
| DATR A3-NSS |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Escitalopram | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 at Week 8 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 over 8 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ramin V. Parsey, MD, PhD | Columbia University | Principal Investigator |
| Jeffrey M Miller, MD | New York State Psychiatric Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Columbia University/New York State Psychiatric Institute | New York | New York | 10032 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23664414 | Derived | 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. |
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MDD subjects who were currently on ineffective medication trial only enrolled if they were able to tolerate a medication washout.
From September 2006 to May 2012, participants were recruited through online or print advertisements, and through referrals from neighboring outpatient clinics.
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| ID | Title | Description |
|---|---|---|
| FG000 | Open Standardized Treatment | Participants will take escitalopram through standardized dosing over an 8 week trial. Non-remitters will be offered entry into a second open treatment phase with standardized treatment with desipramine. In phase 1, participants will receive escitalopram beginning at 10mg daily for 4 weeks, increasing to 20mg if non-response at week 4 or 6. If participants experience intolerable side-effects, they will be switched to an alternative SSRI, sertraline. Non-remitters after 8 weeks may enter a second phase of standardized treatment, switching from escitalopram to desipramine, dosed by blood level according to a treatment protocol. Those with intolerable side-effects to desipramine will be switched to an alternative tricyclic antidepressant, nortriptyline. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SSRI Phase |
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| Tricyclic Phase |
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6 subjects who started on a TCA were also enrolled in the SSRI group (switched groups due to non-remission or side effects). We analyzed data from subjects completing either 6 or 8 weeks of SSRI treatment. Reasons remaining subjects were dropped from analysis included early withdrawal, insufficient PET data and later determination of ineligibility.
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| ID | Title | Description |
|---|---|---|
| BG000 | SSRI | The single arm of this study involves patients with current MDD who will all receive open standardized treatment with escitalopram. There are not multiple arms nor multiple patient groups. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 28 of 38 participants completed the SSRI phase. Only those 28 participants were assessed for remission status. 1 participant who is counted as a non-remitter had a spontaneous remission following his MRI. | Posted | Number | participants | Measured at Week 8 |
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Systematic assessment included structured assessment using clinical global impression (CGI) therapeutic effects item at each treatment visit as well as questions regarding tolerability and side-effects of treatment intervention at each treatment visit.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 1 - SSRI | Participants will take escitalopram. |
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small sample size, homogeneity of sample size
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ramin V. Parsey, MD, PhD | Stony Brook University School of Medicine | 631-444-3084 | Ramin.Parsey@stonybrookmedicine.edu |
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| ID | Term |
|---|---|
| D003863 | Depression |
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
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| ID | Term |
|---|---|
| D000089983 | Escitalopram |
| D003891 | Desipramine |
| ID | Term |
|---|---|
| D011437 | Propylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009570 | Nitriles |
| D001572 |
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| Desipramine | Drug | 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. |
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| 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 at Week 8 |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Participants |
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| Secondary | 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. | Depressed participants who did not remit during the SSRI phase advanced to the tricyclic phase of the study. Five participants started treatment with desipramine, one of which also had a trial with nortriptyline. Two participants started tricyclic treatment with nortriptyline. | Posted | Number | participants | Measured over 8 weeks |
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| Secondary | 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. | Percent improvement of depressive symptoms was calculated for the 28 completers of the SSRI phase. 25 of the 28 SSRI participants completed a trial of escitalopram. 3 of 28 SSRI participants had intolerable side-effects to escitalopram, and were therefore switched to sertraline, and completed a trial of sertraline instead. | Posted | Mean | Standard Deviation | % improvement in depression symptoms | Measured at Week 8 |
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| 0 |
| 37 |
| 0 |
| 37 |
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| D001523 |
| Mental Disorders |
| Benzofurans |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D003984 | Dibenzazepines |
| D006575 | Heterocyclic Compounds, 3-Ring |
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