Depression
Conditions
Keywords
Major Depression, Antidepressants
Brief 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.
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.
Interventions
DRUGEscitalopram
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.
DRUGDesipramine
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.
Sponsors
National Institute of Mental Health (NIMH)
New York State Psychiatric Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Remission of Depressive Symptoms | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Remission of Depressive Symptoms - Tricyclic Phase | Measured over 8 weeks | 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. |
| Improvement in Scores on the Hamilton Depression Rating Scale - SSRI Phase | Measured at Week 8 | 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. |
Countries
United States
Participant flow
Recruitment details
From September 2006 to May 2012, participants were recruited through online or print advertisements, and through referrals from neighboring outpatient clinics.
Pre-assignment details
MDD subjects who were currently on ineffective medication trial only enrolled if they were able to tolerate a medication washout.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 37 |
| Total | 37 |
Baseline characteristics
| Characteristic | SSRI |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants |
| Age, Continuous | 37.35 years STANDARD_DEVIATION 13.61 |
| Region of Enrollment United States | 37 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 37 |
| serious Total, serious adverse events | 0 / 37 |
Outcome results
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.
Time frame: Measured at Week 8
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1 - SSRI | Remission of Depressive Symptoms | Participants achieving remission | 14 participants |
| 1 - SSRI | Remission of Depressive Symptoms | Participants failing to achieve remission | 14 participants |
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.
Time frame: Measured at Week 8
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1 - SSRI | Improvement in Scores on the Hamilton Depression Rating Scale - SSRI Phase | Escitalopram Improvement | 45.46 % improvement in depression symptoms | Standard Deviation 55.95 |
| 1 - SSRI | Improvement in Scores on the Hamilton Depression Rating Scale - SSRI Phase | Sertraline Improvement | 30.01 % improvement in depression symptoms | Standard Deviation 21.87 |
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.
Time frame: Measured over 8 weeks
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1 - SSRI | Remission of Depressive Symptoms - Tricyclic Phase | Number Achieving Remission | 1 participants |
| 1 - SSRI | Remission of Depressive Symptoms - Tricyclic Phase | Numbering Failing to Remit | 3 participants |