Major Depressive Disorder
Conditions
Keywords
Mood Disorder, Depression, Depressive Disorder, Depressive Disorder, Major, Bupropion, Aripiprazole, Remission, Relapse, Cost-Effectiveness, Atypical Antipsychotic, Antidepressant, Augmentation, Veterans, Mental Health
Brief summary
The overall purpose is to determine research based 'next-steps' for outpatients with major depressive disorder who have not had satisfactory outcomes to standard 'first-step' treatments. The primary objective is to compare the acute (up to 12 weeks) treatment effectiveness of augmenting an antidepressant with aripiprazole or with bupropion-slow release (SR) vs. switching treatment to bupropion-SR monotherapy on symptom remission in Veterans with Major Depressive Disorder (MDD) who have not achieved optimal response after an adequate trial on antidepressant (a selective serotonin reuptake inhibitor \[SSRI\] or serotonin and norepinephrine reuptake inhibitor \[SNRI\] or mirtazapine) monotherapy. The secondary objectives are to compare the acute (up to 12 weeks) and long term (up to 36 weeks) efficacy, safety, effects on functioning, suicidality, quality of life, anxiety and other associated symptoms, costs and cost-effectiveness of each of the three treatments.
Detailed description
The overall aim of VAST-D is to enhance treatment outcomes for representative outpatients diagnosed with nonpsychotic major depressive disorder (MDD) and treated in primary or psychiatric VA care settings. In particular, VAST-D is designed to determine the comparative effectiveness of different treatment options for participants with MDD who fail to have a satisfactory outcome to treatment with their initial antidepressants. These options may be conceptualized as representing two overall treatment strategies: 1) Medication Switch - switching from the initial antidepressant to another antidepressant medication, specifically bupropion-SR and 2) Medication Augmentation - augmenting the initial antidepressant with a second antidepressant, specifically bupropion-SR or a second generation antipsychotic, specifically aripiprazole. VAST-D's primary goal is to determine which of these 3 treatment strategies is most likely to lead to remission. Other key objectives include comparisons of response, time to remission, time to response, relapse, anxiety symptoms, suicidal ideation and behaviors, side effects, tolerability, quality of life, health related costs and satisfaction with participation in the study. VAST-D will enroll 1518 total patients of both genders and all ethnic/racial and socioeconomic backgrounds. All patients will meet Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR (text revised) criteria for nonpsychotic MDD. The diagnostic criteria for eligibility will be established by clinical interview supplemented with the 9-item Patient Health Questionnaire (PHQ-9). Final determination for eligibility will be made by the study clinician. Only participants with a suboptimal outcome to a well documented, adequately delivered (dose and duration), trial with selective serotonin reuptake inhibitor (SSRI) or a serotonin and norepinephrine reuptake inhibitor (SNRI) or mirtazapine will be eligible for the study. Failure to achieve an adequate outcome will be ascertained by a score on the 16-item Quick Inventory of Depressive Symptomatology - Clinician rated (QIDS-C16) scale \>= 16 (considered severe depression) after at least 6 weeks of treatment or QIDS-C16 \>= 11 (considered moderately severe depression) after at least 8 weeks of treatment. Otherwise, the inclusion criteria are broad and the exclusion criteria are few; participants with most comorbid general medical or psychiatric disorders are generally included to provide a broadly representative sample. Participants will be randomized (1:1:1 ratio) to switch to bupropion-SR alone (n=506), current antidepressant plus bupropion-SR (n=506), or current antidepressant plus aripiprazole (n=506). Treatment will be guided by clinician-rated symptom measures (the PHQ-9) and global side effects measures (the Frequency, Intensity, and Burden of Side Effects Rating or FIBSER) obtained at each treatment visit. Acute treatment visits will occur at baseline and at weeks 1, 2, 4, 6, 8, 10, and 12 to ensure delivery of appropriate and yet vigorous and tolerable pharmacotherapy. Participants who tolerate the acute treatment and achieve adequate response at 12 weeks will enter the 24-week Continuation Treatment phase, during which the initial treatment will continue and visits will occur every four weeks subsequently until patients have been followed for 36 weeks post-randomization. The QIDS-C16 will be administered at baseline and at each follow-up visit by an independent evaluator (who will be blinded to treatment assignment) to measure symptoms of depression for the study outcomes of remission, response and relapse. Neither the participant nor the treating clinician will be blinded to treatment. Primary hypotheses: Primary hypothesis 1.a: Remission rate from major depressive disorder will be higher in patients whose treatment is augmented with bupropion-SR (antidepressant + bupropion-SR) compared to those switched to bupropion-SR monotherapy. Primary Hypothesis 1.b: Remission rate from major depressive disorder will be higher in patients whose treatment is augmented with aripiprazole (antidepressant + aripiprazole) compared to those switched to bupropion-SR monotherapy. Secondary hypotheses: Secondary Hypothesis 2.a: Remission rate will be greater in patients whose treatment is augmented with bupropion-SR (antidepressant + bupropion-SR) than in those augmented with aripiprazole (antidepressant + aripiprazole). Secondary Hypothesis 2.b: Relapse rate (within 36 weeks of the initiation of treatment) will be lower in patients whose antidepressant is augmented with bupropion-SR (antidepressant + bupropion-SR) than in those whose antidepressant is switched to bupropion-SR monotherapy. Secondary Hypothesis 2.c: Relapse rate (within 36 weeks of the initiation of treatment) will be lower in patients whose treatment is augmented with aripiprazole (antidepressant + aripiprazole) vs. those switched to bupropion-SR monotherapy. Secondary Hypothesis 2.d: Relapse rate (within 36 weeks of the initiation of treatment) will be lower in patients whose treatment is augmented with bupropion-SR (antidepressant + bupropion-SR) than in patients whose treatment was augmented with aripiprazole (antidepressant + aripiprazole). Secondary Hypothesis 2.e: The proportion of patients who develop akathisia, other akathisia-like side effects (e.g., tremor, irritability, motor restlessness) and extrapyramidal side effects will be greater in the patients whose antidepressant treatment is augmented with aripiprazole (antidepressant + aripiprazole) compared to patients whose treatment is augmented with bupropion-SR (antidepressant + bupropion-SR), or switched to bupropion-SR monotherapy. Secondary Hypothesis 2.f: The relative costs (direct and indirect) of augmenting an antidepressant with aripiprazole (antidepressant + aripiprazole) will be greater than the costs of antidepressant augmentation with bupropion-SR (antidepressant + bupropion-SR), and the costs of antidepressant augmentation with bupropion-SR (antidepressant + bupropion-SR) will be greater than the costs of switching to bupropion-SR monotherapy, and augmentation and monotherapy with bupropion-SR will be more cost-effective than aripiprazole augmentation.
Interventions
DRUGSwitching: Bupropion-SR
Bupropion-SR (Dose: 150 mg - 400 mg taken per day orally for up to 36 weeks): Initiating with bupropion-SR dose of 150 mg, then increasing dose per protocol up to 400 mg (200 mg BID), maintaining or decreasing dose for up to 36 weeks depending on response and side effect profile through the acute and continuation phases.
DRUGAugmenting: Antidepressant + Bupropion-SR
Current antidepressant (either a SSRI or a SNRI or mirtazapine): Continue the dose prescribed at time of enrollment, or adjust depending on response or side effect profile for up to 36 weeks. And Bupropion-SR (Dose: 150 mg - 400 mg taken per day orally for up to 36 weeks): Initiating with bupropion-SR dose of 150 mg, then increasing dose per protocol up to 400 mg (200 mg BID), maintaining or decreasing dose for up to 36 weeks depending on response and side effect profile through the acute and continuation phases.
DRUGAugmenting: Antidepressant + Aripiprazole
Current antidepressant (either a SSRI or a SNRI or mirtazapine): Continue the dose prescribed at time of enrollment or adjust depending on response or side effect profile for up to 36 weeks. And Aripiprazole (Dose: 2 mg - 15 mg taken orally once per day for up to 36 weeks): Initiating with aripiprazole dose of 2 mg for one week, then increasing dose per protocol up to 15 mg, maintaining or decreasing dose for up to 36 weeks depending on response and side effect profile through the acute and continuation phases.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* DSM-IV diagnosis of single or recurrent, non-psychotic, major depressive disorder * Currently taking a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) or mirtazapine for major depressive disorder * Need for next-step treatment based on documented suboptimal outcome from current antidepressant treatment for major depressive episode (at least 6 weeks treatment with a QIDS-C16 \>= 16 or at least 8 weeks with a QIDS-C16 \>= 11; and at least 3 weeks at a stable optimal dose * Age: 18 years of age or older
Exclusion criteria
* Prior inadequate response after an adequate treatment trial or clear cut intolerance to either of the study medications (aripiprazole or bupropion) * Current treatment with bupropion, aripiprazole or any other antipsychotic agent * Lifetime history of bipolar disorder, schizophrenia, schizoaffective disorder, or psychosis not otherwise specified * Current diagnosis of Dementia * Current diagnosis of an eating disorder or a seizure disorder * High suicide risk currently requiring acute intervention (other than outpatient treatment of depression) * Unstable, serious medical condition or one requiring acute medical treatment, or anticipation of hospitalization for extended care * Requiring immediate hospitalization for psychiatric disorders * Physiologic substance dependence requiring detoxification (excluding nicotine) in the past 30 days (substance abuse is not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Protocol Remission of Symptoms of Major Depressive Disorder | During acute phase (12 weeks) | Remission of symptoms of major depression during the acute treatment phase (12 weeks) defined as a sustained clinician-rated Quick Inventory of Depressive Symptoms (QIDS-C16) of \<= 5 for two consecutive visits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Protocol Relapse of Symptoms of Major Depression After Achieving Remission in the Acute Phase | Within 36 weeks after randomization (initiation of treatment) | Relapse in symptoms of major depression defined as a QIDS-C16 =\> 11 among those achieving remission in the acute phase. |
| Rate of Protocol Response as Reduction in Symptoms of Major Depression (>= 50% Reduction in QIDS-C) | During acute phase (up to 12 weeks) | Response measured as reduction in symptom score for major depression defined as: 1. a reduction in QIDS-C16 of 50% or greater |
| Rate of Protocol Response Measured as a Change in Clinical Global Impression (CGI) - Improvement Scale | During acute phase (up to 12 weeks) | Clinical assessment of a participant's level of depression and treatment response assessed by the Clinical Global Impression - Improvement (CGI -I) Scale, a 7-point clinician rating scale of improvement from baseline in severity of depression (Guy 1976). A secondary outcome measure of response was defined as achieving a score of 2 (much improved) or 1 (very much improved). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Switching: Bupropion-SR Switching: Bupropion-SR: Bupropion-SR (Dose: 150 mg - 400 mg taken per day orally for up to 36 weeks): Initiating with bupropion-SR dose of 150 mg, then increasing dose per protocol up to 400 mg (200 mg BID), maintaining or decreasing dose for up to 36 weeks depending on response and side effect profile through the acute and continuation phases. | 511 |
| Augmenting: Antidepressant + Bupropion-SR Augmenting: Antidepressant + Bupropion-SR: Current antidepressant (either a SSRI or a SNRI or mirtazapine): Continue the dose prescribed at time of enrollment, or adjust depending on response or side effect profile for up to 36 weeks.
And
Bupropion-SR (Dose: 150 mg - 400 mg taken per day orally for up to 36 weeks): Initiating with bupropion-SR dose of 150 mg, then increasing dose per protocol up to 400 mg (200 mg BID), maintaining or decreasing dose for up to 36 weeks depending on response and side effect profile through the acute and continuation phases. | 506 |
| Augmenting: Antidepressant + Aripiprazole Augmenting: Antidepressant + Aripiprazole: Current antidepressant (either a SSRI or a SNRI or mirtazapine): Continue the dose prescribed at time of enrollment or adjust depending on response or side effect profile for up to 36 weeks.
And
Aripiprazole (Dose: 2 mg - 15 mg taken orally once per day for up to 36 weeks): Initiating with aripiprazole dose of 2 mg for one week, then increasing dose per protocol up to 15 mg, maintaining or decreasing dose for up to 36 weeks depending on response and side effect profile through the acute and continuation phases. | 505 |
| Total | 1,522 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Acute Treatment Phase (12 Weeks) | Adverse Event | 53 | 38 | 27 |
| Acute Treatment Phase (12 Weeks) | Death | 0 | 0 | 3 |
| Acute Treatment Phase (12 Weeks) | Dure to other illness | 3 | 2 | 4 |
| Acute Treatment Phase (12 Weeks) | Lack of Efficacy | 49 | 28 | 13 |
| Acute Treatment Phase (12 Weeks) | Lost to Follow-up | 6 | 18 | 21 |
| Acute Treatment Phase (12 Weeks) | Non-adherence | 15 | 7 | 13 |
| Acute Treatment Phase (12 Weeks) | Other reason for withdrawal | 8 | 9 | 4 |
| Acute Treatment Phase (12 Weeks) | Participant moved away | 1 | 6 | 1 |
| Acute Treatment Phase (12 Weeks) | Withdrawal by Subject | 23 | 20 | 13 |
| Completed to Week 12 But Then Withdrawn | Adverse Event | 4 | 3 | 6 |
| Completed to Week 12 But Then Withdrawn | Due to Other Illness | 1 | 0 | 2 |
| Completed to Week 12 But Then Withdrawn | End of Study Time | 0 | 0 | 2 |
| Completed to Week 12 But Then Withdrawn | Lack of Efficacy | 111 | 93 | 88 |
| Completed to Week 12 But Then Withdrawn | Lost to Follow-up | 4 | 3 | 3 |
| Completed to Week 12 But Then Withdrawn | Non-adherence | 5 | 4 | 5 |
| Completed to Week 12 But Then Withdrawn | Oher reason for withdrawal | 3 | 3 | 4 |
| Completed to Week 12 But Then Withdrawn | Participant Moved Away | 1 | 5 | 5 |
| Completed to Week 12 But Then Withdrawn | QIDS Score >=11 | 7 | 10 | 12 |
| Completed to Week 12 But Then Withdrawn | Withdrawal by Subject | 13 | 4 | 11 |
| Continuation of Treatment (Week 12 - 36) | Adverse Event | 0 | 6 | 11 |
| Continuation of Treatment (Week 12 - 36) | Due to Other Illness | 2 | 2 | 2 |
| Continuation of Treatment (Week 12 - 36) | End of Study Time | 15 | 20 | 14 |
| Continuation of Treatment (Week 12 - 36) | Lack of Efficacy | 11 | 5 | 11 |
| Continuation of Treatment (Week 12 - 36) | Lost to Follow-up | 4 | 11 | 9 |
| Continuation of Treatment (Week 12 - 36) | Non-adherence | 3 | 8 | 4 |
| Continuation of Treatment (Week 12 - 36) | Other reason for withdrawal | 6 | 0 | 7 |
| Continuation of Treatment (Week 12 - 36) | Participant moved away | 4 | 1 | 3 |
| Continuation of Treatment (Week 12 - 36) | Withdrawal by Subject | 7 | 6 | 4 |
Baseline characteristics
| Characteristic | Total | Switching: Bupropion-SR | Augmenting: Antidepressant + Aripiprazole | Augmenting: Antidepressant + Bupropion-SR |
|---|---|---|---|---|
| Age, Continuous | 54.4 years STANDARD_DEVIATION 12.2 | 54.5 years STANDARD_DEVIATION 12.2 | 54.2 years STANDARD_DEVIATION 12.3 | 54.4 years STANDARD_DEVIATION 12.2 |
| Arizona Sexual Experiences Scale (Female) | 4.2 participants STANDARD_DEVIATION 1.1 | 4.2 participants STANDARD_DEVIATION 1.1 | 4.2 participants STANDARD_DEVIATION 1.2 | 4.2 participants STANDARD_DEVIATION 1.1 |
| Arizona Sexual Experiences Scale (male) | 4.1 participants STANDARD_DEVIATION 1.1 | 4.1 participants STANDARD_DEVIATION 1.1 | 4.1 participants STANDARD_DEVIATION 1.2 | 4.1 participants STANDARD_DEVIATION 1.1 |
| Beck Anxiety Inventory | 19.1 units on a scale STANDARD_DEVIATION 11.3 | 18.6 units on a scale STANDARD_DEVIATION 11.1 | 19.7 units on a scale STANDARD_DEVIATION 11.3 | 19.0 units on a scale STANDARD_DEVIATION 11.4 |
| CGI - Severity Score | 4.6 units on a scale STANDARD_DEVIATION 1 | 4.5 units on a scale STANDARD_DEVIATION 1 | 4.6 units on a scale STANDARD_DEVIATION 1 | 4.6 units on a scale STANDARD_DEVIATION 0.9 |
| Cumulative Illness Rating Scale (CIRS) Severity Index | 11.2 units on a scale STANDARD_DEVIATION 5.2 | 11.4 units on a scale STANDARD_DEVIATION 5.5 | 11.0 units on a scale STANDARD_DEVIATION 5.1 | 11.1 units on a scale STANDARD_DEVIATION 4.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1362 Participants | 454 Participants | 459 Participants | 449 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 157 Participants | 57 Participants | 45 Participants | 55 Participants |
| EuroQol Health State Score | 53.8 units on a scale STANDARD_DEVIATION 20.4 | 54.7 units on a scale STANDARD_DEVIATION 20.5 | 54.0 units on a scale STANDARD_DEVIATION 20.8 | 52.7 units on a scale STANDARD_DEVIATION 19.8 |
| Patient Health Questionnaire (PHQ-9) | 16.2 units on a scale STANDARD_DEVIATION 5.2 | 15.9 units on a scale STANDARD_DEVIATION 5.2 | 16.3 units on a scale STANDARD_DEVIATION 5.2 | 16.3 units on a scale STANDARD_DEVIATION 5.2 |
| PTSD | 717 Participants | 248 Participants | 225 Participants | 244 Participants |
| QIDS-C16 Score | 16.7 units on a scale STANDARD_DEVIATION 3.3 | 16.6 units on a scale STANDARD_DEVIATION 3.3 | 16.9 units on a scale STANDARD_DEVIATION 3.3 | 16.6 units on a scale STANDARD_DEVIATION 3.2 |
| Quality of Life Enjoyment and Satisfaction Score | 40.6 units on a scale STANDARD_DEVIATION 14.5 | 41.4 units on a scale STANDARD_DEVIATION 13.8 | 40.1 units on a scale STANDARD_DEVIATION 14.8 | 40.3 units on a scale STANDARD_DEVIATION 14.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 22 Participants | 8 Participants | 6 Participants | 8 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 2 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 370 Participants | 129 Participants | 126 Participants | 115 Participants |
| Race (NIH/OMB) More than one race | 43 Participants | 10 Participants | 13 Participants | 20 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants | 2 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 53 Participants | 19 Participants | 17 Participants | 17 Participants |
| Race (NIH/OMB) White | 1022 Participants | 341 Participants | 338 Participants | 343 Participants |
| Sex: Female, Male Female | 226 Participants | 68 Participants | 77 Participants | 81 Participants |
| Sex: Female, Male Male | 1296 Participants | 443 Participants | 428 Participants | 425 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 511 | 1 / 506 | 4 / 505 |
| other Total, other adverse events | 383 / 511 | 369 / 506 | 374 / 505 |
| serious Total, serious adverse events | 52 / 511 | 57 / 506 | 56 / 505 |
Outcome results
Primary
Rate of Protocol Remission of Symptoms of Major Depressive Disorder
Remission of symptoms of major depression during the acute treatment phase (12 weeks) defined as a sustained clinician-rated Quick Inventory of Depressive Symptoms (QIDS-C16) of \<= 5 for two consecutive visits.
Time frame: During acute phase (12 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Switching: Bupropion-SR | Rate of Protocol Remission of Symptoms of Major Depressive Disorder | 114 Participants |
| Augmenting: Antidepressant + Bupropion-SR | Rate of Protocol Remission of Symptoms of Major Depressive Disorder | 136 Participants |
| Augmenting: Antidepressant + Aripiprazole | Rate of Protocol Remission of Symptoms of Major Depressive Disorder | 146 Participants |
p-value: 0.07695% CI: [0.97, 1.75]Regression, Logistic
Comparison: Co-primary hypothesis: After ordering results form largest p-value to smallest (Hochberg approach) the comparison of Augmentation Antidepressant + Aripiprazole with Switching to Bupropion-SR was performed at the 0.025 significance level.p-value: 0.01895% CI: [1.06, 1.89]Regression, Logistic
Comparison: If either if the first two hypothesis tests for the co-primary hypotheses were significant, perform the test of Augmentation Antidepressant + Aripiprazole vs. Augmentation Antidepressant + Bupropion-SR at the 0.05 significance level.p-value: 0.4695% CI: [0.84, 1.48]Regression, Logistic
Secondary
Rate of Protocol Relapse of Symptoms of Major Depression After Achieving Remission in the Acute Phase
Relapse in symptoms of major depression defined as a QIDS-C16 =\> 11 among those achieving remission in the acute phase.
Time frame: Within 36 weeks after randomization (initiation of treatment)
Population: The Analysis Population is the cohort of participants who met the criteria for protocol remission during the Acute Phase (first 12 Weeks of follow-up)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Switching: Bupropion-SR | Rate of Protocol Relapse of Symptoms of Major Depression After Achieving Remission in the Acute Phase | 26 Participants |
| Augmenting: Antidepressant + Bupropion-SR | Rate of Protocol Relapse of Symptoms of Major Depression After Achieving Remission in the Acute Phase | 35 Participants |
| Augmenting: Antidepressant + Aripiprazole | Rate of Protocol Relapse of Symptoms of Major Depression After Achieving Remission in the Acute Phase | 37 Participants |
p-value: 0.795% CI: [0.78, 2.39]Log Rank
p-value: 0.6895% CI: [0.65, 1.94]Log Rank
p-value: 0.8795% CI: [0.58, 1.59]Log Rank
Secondary
Rate of Protocol Response as Reduction in Symptoms of Major Depression (>= 50% Reduction in QIDS-C)
Response measured as reduction in symptom score for major depression defined as: 1. a reduction in QIDS-C16 of 50% or greater
Time frame: During acute phase (up to 12 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Switching: Bupropion-SR | Rate of Protocol Response as Reduction in Symptoms of Major Depression (>= 50% Reduction in QIDS-C) | 319 Participants |
| Augmenting: Antidepressant + Bupropion-SR | Rate of Protocol Response as Reduction in Symptoms of Major Depression (>= 50% Reduction in QIDS-C) | 332 Participants |
| Augmenting: Antidepressant + Aripiprazole | Rate of Protocol Response as Reduction in Symptoms of Major Depression (>= 50% Reduction in QIDS-C) | 375 Participants |
Comparison: After ordering results form largest p-value to smallest (Hochberg approach) the comparison of Augmentation Antidepressant + Bupropion with Switching to Bupropion was performed at the 0.05 significance level.p-value: 0.2895% CI: [0.89, 1.5]Regression, Logistic
Comparison: After ordering results form largest p-value to smallest (Hochberg approach) the comparison of Augmentation Antidepressant + Aripiprazole with Switching to Bupropion-SR was performed at the 0.025 significance level.p-value: <0.000195% CI: [1.33, 2.29]Regression, Logistic
p-value: 0.00295% CI: [1.17, 2.05]Regression, Logistic
Secondary
Rate of Protocol Response Measured as a Change in Clinical Global Impression (CGI) - Improvement Scale
Clinical assessment of a participant's level of depression and treatment response assessed by the Clinical Global Impression - Improvement (CGI -I) Scale, a 7-point clinician rating scale of improvement from baseline in severity of depression (Guy 1976). A secondary outcome measure of response was defined as achieving a score of 2 (much improved) or 1 (very much improved).
Time frame: During acute phase (up to 12 weeks)
Population: Whole randomized cohort by intent-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Switching: Bupropion-SR | Rate of Protocol Response Measured as a Change in Clinical Global Impression (CGI) - Improvement Scale | 356 Participants |
| Augmenting: Antidepressant + Bupropion-SR | Rate of Protocol Response Measured as a Change in Clinical Global Impression (CGI) - Improvement Scale | 376 Participants |
| Augmenting: Antidepressant + Aripiprazole | Rate of Protocol Response Measured as a Change in Clinical Global Impression (CGI) - Improvement Scale | 400 Participants |
p-value: 0.1195% CI: [0.95, 1.68]Regression, Logistic
Comparison: After ordering results form largest p-value to smallest (Hochberg approach) the comparison of Augmentation Antidepressant + Aripiprazole with Switching to Bupropion-SR was performed at the 0.025 significance level.p-value: <0.00195% CI: [1.26, 2.29]Regression, Logistic
p-value: 0.04395% CI: [1.01, 1.86]Regression, Logistic