Major Depressive Disorder
Conditions
Keywords
cognitive function, psychosocial function, augmentation, treatment refractory depression
Brief summary
Our target population will have been adequately treated with one of three selective serotonin reuptake inhibitors (SSRIs; escitalopram, citalopram, or sertraline) for at least 8-12 weeks and continue to experience symptoms of depression that have prompted them to seek additional treatment. Escitalopram, citalopram, and sertraline were selected for use in this study because they are among the most commonly selected SSRIs and they are associated with a reduced likelihood of drug-drug interactions with aripiprazole. After completion of the screening process, eligible participants will be augmented with aripiprazole (5, 10, or 15 mg) for 6 weeks. Participants will continue SSRI treatment with their prescribing physician, in conjunction with study participation. Symptom severity will be assessed on a weekly basis, and cognitive and psychosocial function will be assessed at pre- and post-augmentation. We hypothesize that aripiprazole augmentation will be associated with reductions in symptom severity, and with improved performance on measures of psychosocial and cognitive function.
Interventions
DRUGAripiprazole
varied dose (5, 10, 15 mg qd) for 6 wks
Sponsors
Bristol-Myers Squibb
University of Texas Southwestern Medical Center
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
* Age 18-65 * Primary diagnosis of Major Depressive Disorder (MDD) * Completion of at least 8-12 weeks (and no longer than 6 months) of treatment with escitalopram, citalopram, or sertraline, with at least 6 weeks at an adequate dose (i.e., 20 mg escitalopram; 40 mg citalopram; 150 mg sertraline) * Hamilton Rating Scale for Depression, 17-item (HRSD17) score less than or equal to 14 and/or Clinical Global Impression - Severity (CGI-S) score less than or equal to 3 * Self-reported difficulties with cognition and/or concentration, and an Inventory for Depressive Symptomatology Clinician-Rated, 30-item (IDS-C30) item #16 (Concentration and Decision Making) score less than or equal to 2 * Ability to read and write in English (required because instructions for cognitive testing and several questionnaires are available only in English)
Exclusion criteria
* Presence of untreated or unstable comorbid medical condition based on physician information or evidence at examination, such as hypertension, diabetes, hypothyroidism. * Presence of known cardiovascular disease or seizure disorder. * Presence of other primary psychiatric disorders or conditions (including depression due to medical conditions, currently suicidal or high suicide risk, current or past psychotic disorders of any type, bipolar disorder (I, II, or Not Otherwise Specified \[NOS\]), schizophrenia, schizoaffective disorder, anorexia, bulimia, obsessive compulsive disorder, alcohol or substance abuse or dependence within the last 6 months) * Presence of organic brain injury or dementia, based on a cutoff score of \< 20 on the Mini Mental Status Examination (MMSE). * Concomitant pharmacological or psychotherapeutic treatment (in addition to one SSRI as described in Inclusion Criteria) including but not limited to anxiolytics, neuroleptics, mood stabilizers * Hospitalization for mental illness within the past year. * For women, currently pregnant or planning to become pregnant in the next year.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stockings of Cambridge (SOC) Mean Initial Thinking Time for 3-move Problems | baseline and 6 weeks | The SOC is part of the CAmbridge Neuropsychological Test Automated Battery (CANTAB) and is an executive function task based on the Tower of London test that assesses spatial planning for problems with 2, 3, 4, or 5 moves. The Mean Initial Thinking Time for 3-move problems is the time (in milliseconds)taken to plan a problem solution for trials requiring 3 moves. Higher numbers indicate poorer performance. Time reported is the difference between baseline and 6 weeks post-treatment. |
| Stockings of Cambridge (SOC) Mean Initial Thinking Time for 5-move Problems | baseline and 6 weeks | The SOC is part of the CAmbridge Neuropsychological Test Automated Battery (CANTAB) and is an executive function task based on the Tower of London test that assesses spatial planning for problems with 2, 3, 4, or 5 moves. The Mean Initial Thinking Time for 5-move problems is the time (in milliseconds) taken to plan a problem solution for trials requiring 5 moves. Higher numbers indicate poorer performance. Time reported is the difference between baseline and 6 weeks post-treatment. |
| Spatial Working Memory (SWM) Between Errors for 6-move Problems | baseline and 6 weeks | The SWM task is part of the CANTAB neruopsychological test battery and is an executive function task assessing retention and manipulation of items in working memory, with the ability for assessment of perseverative (redundant) errors. Between errors are times the subject revisits a box in which a token was previously found; errors are calculated for 4-, 6-, and 8-box trials. Higher numbers indicate poorer performance. Errors reported are the difference between baseline and 6 weeks post-treatment. |
| Spatial Working Memory (SWM) Strategy Score | baseline and 6 weeks | The SWM task is part of the CANTAB neruopsychological test battery and is an executive function task assessing retention and manipulation of items in working memory, with the ability for assessment of perseverative (redundant) errors. The Strategy score represents the number of times a participant begins a search with the same box for 6- and 8-box problems. Minimum score is 8 and maximum score is 56. Higher numbers indicate poorer performance. Score reported is the difference between baseline and 6 weeks post-treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life Enjoyment and Satisfaction Questionnaire | 6 weeks | The Q-LES-Q general activities is designed to measure subjective satisfaction and enjoyment, as opposed to function, in various domains including physical health, feelings, work, household duties, school/course work, leisure time activities, social relations, and general activities. The raw score is converted into a percent of the maximum possible score and range from 0 to 100. Higher scores indicate greater enjoyment and satisfaction. |
| Change in Hamilton Rating Scale for Depression (HRSD - 17-item) | 6 weeks | The HRSD 17-item scale is a clinician-administered rating scale designed to assess the severity of symptoms in patients diagnosed with depression. Scores range from 0 to 52, with higher scores indicating higher levels of depression severity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open-label Aripiprazole Augmentation Aripiprazole augmentation of existing escitalopram, citalopram, or sertraline treatment was provided to study participants at a flexible dose between 5-15 mg (based on clinical symptoms and side effects) for 6 weeks | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
Baseline characteristics
| Characteristic | Open-label Aripiprazole Augmentation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age Continuous | 48.18 years STANDARD_DEVIATION 7.95 |
| Region of Enrollment United States | 17 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 17 |
| serious Total, serious adverse events | 0 / 17 |
Outcome results
Primary
Spatial Working Memory (SWM) Between Errors for 6-move Problems
The SWM task is part of the CANTAB neruopsychological test battery and is an executive function task assessing retention and manipulation of items in working memory, with the ability for assessment of perseverative (redundant) errors. Between errors are times the subject revisits a box in which a token was previously found; errors are calculated for 4-, 6-, and 8-box trials. Higher numbers indicate poorer performance. Errors reported are the difference between baseline and 6 weeks post-treatment.
Time frame: baseline and 6 weeks
Population: Completers because data were collected pre- and post-treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open Label Aripiprazole Augmentation | Spatial Working Memory (SWM) Between Errors for 6-move Problems | -4.00 number of errors | Standard Deviation 4.67 |
Primary
Spatial Working Memory (SWM) Strategy Score
The SWM task is part of the CANTAB neruopsychological test battery and is an executive function task assessing retention and manipulation of items in working memory, with the ability for assessment of perseverative (redundant) errors. The Strategy score represents the number of times a participant begins a search with the same box for 6- and 8-box problems. Minimum score is 8 and maximum score is 56. Higher numbers indicate poorer performance. Score reported is the difference between baseline and 6 weeks post-treatment.
Time frame: baseline and 6 weeks
Population: Completers; due to fact that testing occurred at pre- and post-intervention; mean represents difference between pre- and post-intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open Label Aripiprazole Augmentation | Spatial Working Memory (SWM) Strategy Score | -3.15 units on a scale | Standard Deviation 4.52 |
Primary
Stockings of Cambridge (SOC) Mean Initial Thinking Time for 3-move Problems
The SOC is part of the CAmbridge Neuropsychological Test Automated Battery (CANTAB) and is an executive function task based on the Tower of London test that assesses spatial planning for problems with 2, 3, 4, or 5 moves. The Mean Initial Thinking Time for 3-move problems is the time (in milliseconds)taken to plan a problem solution for trials requiring 3 moves. Higher numbers indicate poorer performance. Time reported is the difference between baseline and 6 weeks post-treatment.
Time frame: baseline and 6 weeks
Population: Completers; due to fact that testing occurred at pre- and post-intervention; mean represents difference between pre- and post-intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open Label Aripiprazole Augmentation | Stockings of Cambridge (SOC) Mean Initial Thinking Time for 3-move Problems | -4485.50 milliseconds | Standard Deviation 6279.4 |
Primary
Stockings of Cambridge (SOC) Mean Initial Thinking Time for 5-move Problems
The SOC is part of the CAmbridge Neuropsychological Test Automated Battery (CANTAB) and is an executive function task based on the Tower of London test that assesses spatial planning for problems with 2, 3, 4, or 5 moves. The Mean Initial Thinking Time for 5-move problems is the time (in milliseconds) taken to plan a problem solution for trials requiring 5 moves. Higher numbers indicate poorer performance. Time reported is the difference between baseline and 6 weeks post-treatment.
Time frame: baseline and 6 weeks
Population: Completers; due to fact that testing occurred at pre- and post-intervention; mean represents difference between pre- and post-intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open Label Aripiprazole Augmentation | Stockings of Cambridge (SOC) Mean Initial Thinking Time for 5-move Problems | -4676.10 milliseconds | Standard Deviation 8604.16 |
Secondary
Change in Hamilton Rating Scale for Depression (HRSD - 17-item)
The HRSD 17-item scale is a clinician-administered rating scale designed to assess the severity of symptoms in patients diagnosed with depression. Scores range from 0 to 52, with higher scores indicating higher levels of depression severity.
Time frame: 6 weeks
Population: Study completers who completed the HRSD pre- and post-intervention; mean represents mean difference from pre- to post-intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open Label Aripiprazole Augmentation | Change in Hamilton Rating Scale for Depression (HRSD - 17-item) | -11.42 units on a scale | Standard Deviation 4.5 |
Secondary
Quality of Life Enjoyment and Satisfaction Questionnaire
The Q-LES-Q general activities is designed to measure subjective satisfaction and enjoyment, as opposed to function, in various domains including physical health, feelings, work, household duties, school/course work, leisure time activities, social relations, and general activities. The raw score is converted into a percent of the maximum possible score and range from 0 to 100. Higher scores indicate greater enjoyment and satisfaction.
Time frame: 6 weeks
Population: Study completers who completed the Q-LES-Q pre- and post-intervention; mean represents mean difference from pre- to post-intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open Label Aripiprazole Augmentation | Quality of Life Enjoyment and Satisfaction Questionnaire | 0.81 units on a scale | Standard Deviation 0.48 |