Depressive Disorder, Major
Conditions
Keywords
Major Depression, Depression, Unipolar Depression, Treatment Resistant Depression, Adjunctive treatment
Brief summary
This is a study of the effectiveness of adding Abilify (aripiprazole), an atypical antipsychotic medication, to ongoing selective serotonin reuptake inhibitor (SSRI) antidepressant treatment for depressed outpatients who are not responding fully to SSRI treatment alone. It is hypothesized that patients' functioning will improve after 12 weeks of treatment with Aripiprazole and SSRI medication.
Detailed description
This is a pilot study of the effectiveness of adding Abilify (aripiprazole), an atypical antipsychotic medication, to ongoing selective serotonin reuptake inhibitor (SSRI) antidepressant treatment for depressed outpatients who are not responding fully to SSRI treatment alone. Fifteen subjects will be given aripiprazole in a flexible dosing schedule and followed for 12 weeks, while continuing their ongoing SSRI medication. Assessments of depressive symptoms, overall functioning, social functioning, and side effects will be completed. It is hypothesized that patients' functioning will improve after 12 weeks of treatment with Aripiprazole and SSRI medication.
Interventions
DRUGAripiprazole
Aripiprazole dose ranging from 5 to 30 mg/day, augmenting antidepressant treatment. Aripiprazole is used as an augmenting medication on an open label basis for patients on antidepressant medication who continue to have depressive symptoms. This is an open label case series in which all subjects receive aripiprazole augmentation. There is no comparator group.
Sponsors
Bristol-Myers Squibb
St. Luke's-Roosevelt Hospital Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male and female outpatients between the ages of 18 and 70. * Patients with a principal Diagnostic and Statistical Manual fourth edition (DSM-IV) diagnosis of Major Depressive Disorder, unipolar, nonpsychotic type * Patients with a total of 14 or higher on the 17-item Hamilton Depression Scale at baseline * Patients who have had treatment with an SSRI at an adequate dose (see Table for a minimum of 6 weeks (i.e. 6 wks at the dose defined as adequate in Table 2) * Patients who agree to use acceptable method of birth control throughout the study
Exclusion criteria
* Patients with any of the following DSM-IV diagnoses: Delirium, Dementia, Amnestic, or other Cognitive Disorders. Bipolar Disorder or cyclothymia, Schizophrenia, Delusional (Paranoid) Disorders and Psychotic Disorders not elsewhere classified, Severe Borderline Personality Disorder, Anorexia Nervosa, or Bulimia. * Patients who, within the past 6 months, met DSM-IV criteria for abuse of or dependence on any drug, including alcohol. * Patients who are pregnant or nursing women. * Patients who would pose a serious risk for suicide during the course of the study, as evidenced by one of the following: (a) report of having a specific plan for killing themselves, (b) a score of 3 or higher on the Hamilton Depression Rating Scale item #3 as rated by the treating clinician at Week 0, or (c) a suicide attempt within the last 6 months which required medical attention, such as an emergency room visit or which is considered by the treating physician to have been possibly life threatening * Patients with unstable medical conditions such as untreated or uncontrolled hyperthyroidism, hypothyroidism, hypertension (defined as blood pressure\>150/90), cardiovascular disease, diabetes, HIV (by report of patient). * Patients with a history of seizures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Rating Scale (HDRS) | 12 weeks | Clinician rated measure of depression, mean score; this study used the 24 item version of the Hamilton Depression Rating Scale; item scores range from 0 to 4 on some items, 0 to 2 or 0 to 3 on other items; range of total score = 0 to 75, with higher score indicating worse depression Response (\>50% decrease) Remission (score\<=7) Outcome is the number of these subjects whose depression responded after treatment with aripiprazole, which means a 50% or greater decrease in Hamilton Depression Rating Scale scores at week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impressions Improvement Scale (CGI) | 12 weeks | clinician rated improvement, score on CGI scale ranging from 1 (very much improved) to 7 (very much worse) |
| Change in Global Assessment of Functioning Scale (GAFS) | baseline and 12 weeks | Ranging from 0 to 100, with higher score indicating better global functioning. Outcome is the post-treatment GAFS score compared to the pre-treatment GAFS score. |
| Change in Beck Depression Inventory (BDI) Score | baseline and 12 weeks | 21 item patient rated assessment of depression symptoms, with item scores ranging from 0 to 3. Total BDI scores can range from 0 to 63, with higher scores indicating worse depression. Outcome is the subject's total BDI score post-treatment compared to the subject's total BDI score pre-treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aripiprazole aripiprazole augmentation treatment | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Aripiprazole |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Age, Continuous | 46 years STANDARD_DEVIATION 13 |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Hamilton Depression Rating Scale (HDRS)
Clinician rated measure of depression, mean score; this study used the 24 item version of the Hamilton Depression Rating Scale; item scores range from 0 to 4 on some items, 0 to 2 or 0 to 3 on other items; range of total score = 0 to 75, with higher score indicating worse depression Response (\>50% decrease) Remission (score\<=7) Outcome is the number of these subjects whose depression responded after treatment with aripiprazole, which means a 50% or greater decrease in Hamilton Depression Rating Scale scores at week 12.
Time frame: 12 weeks
Population: Adults with treatment resistant depression, all subjects with data after baseline (14 of 15 subjects).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aripiprazole | Hamilton Depression Rating Scale (HDRS) | 7 participants |
Comparison: Null hypothesis would be no change in the HDRS score pre- to post- treatment with aripiprazole.p-value: <0.001t-test, 2 sided
Secondary
Change in Beck Depression Inventory (BDI) Score
21 item patient rated assessment of depression symptoms, with item scores ranging from 0 to 3. Total BDI scores can range from 0 to 63, with higher scores indicating worse depression. Outcome is the subject's total BDI score post-treatment compared to the subject's total BDI score pre-treatment.
Time frame: baseline and 12 weeks
Population: Number of participants for whom data was available after starting aripiprazole augmentation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole | Change in Beck Depression Inventory (BDI) Score | 4.2 points on BDI scale | Standard Deviation 10 |
Comparison: Null hypothesis would be no change in the BDI score pre- to post- treatment with aripiprazole.p-value: 0.008t-test, 2 sided
Secondary
Change in Global Assessment of Functioning Scale (GAFS)
Ranging from 0 to 100, with higher score indicating better global functioning. Outcome is the post-treatment GAFS score compared to the pre-treatment GAFS score.
Time frame: baseline and 12 weeks
Population: All subjects (14/15) for whom data was available after starting aripiprazole augmentation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole | Change in Global Assessment of Functioning Scale (GAFS) | 7.3 points on GAFS scale | Standard Deviation 4.7 |
Comparison: Null hypothesis would be no change in the GAFS score pre- to post- treatment with aripiprazole.p-value: 0.009t-test, 2 sided
Secondary
Clinical Global Impressions Improvement Scale (CGI)
clinician rated improvement, score on CGI scale ranging from 1 (very much improved) to 7 (very much worse)
Time frame: 12 weeks
Population: all subjects for whom data was available after beginning aripiprazole augmentation (14 of 15 subjects)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole | Clinical Global Impressions Improvement Scale (CGI) | 2.8 units on CGI scale | Standard Deviation 1.1 |