A Double-Blind, Placebo-Controlled Study of Aripiprazole Adjunctive to Antidepressant Therapy (ADT) Among Outpatients With Major Depressive Disorder Who Have Responded Inadequately to Prior ADT
Overview
- Phase
- Phase 3
- Intervention
- Aripiprazole 5mg
- Conditions
- Major Depressive Disorder
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 225
- Locations
- 1
- Primary Endpoint
- MADRS (Montgomery-Asberg Depression Rating Scale) Response Rate
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The purpose of this study is to determine whether a reduced dose of aripiprazole is effective in treating patients with major depressive disorder
Detailed Description
This is a 60-day, multi-center, double-blind, placebo-controlled study on the efficacy of aripiprazole (Abilify) augmentation of selective serotonin reuptake inhibitors (SSRIs) or selective serotonin norepinephrine uptake inhibitors (SNRIs) venlafaxine in patients with MDD who have responded inadequately to treatment with ADTs. The purpose of our study is to evaluate the efficacy and tolerability of low-dose (2 mg/day) aripiprazole (Abilify) as an augmentation strategy in MDD non-responding to ADT with SSRIs or the SNRI venlafaxine.
Investigators
Maurizio Fava, MD
Executive Vice Chair, Department of Psychiatry; Executive Director, Clinical Trials Network and Institute (CTNI); Director, Depression Clinical and Research Program (DCRP)
Massachusetts General Hospital
Eligibility Criteria
Inclusion Criteria
- •Patients able to give informed consent, and/or consent obtained from a legally acceptable representative (as required by IRB/IEC), prior to the initiation of any protocol required procedures.
- •Patients must be able to understand the nature of the study, agree to comply with the prescribed dosage regimens, report for regularly scheduled office visits, and communicate to study personnel about adverse events and concomitant medication use.
- •Patients with a diagnosis of major depressive episode as defined by DSM-IV-TR criteria, based on the SCID-I/P; their major depressive episode must be deemed "valid" using the SAFER criteria interview administered by remote, independent raters.
- •Patients who have reported a history for the current depressive episode of an inadequate response to at least one and no more than three adequate antidepressant treatments. An inadequate response is defined as less than a 50% reduction in depressive symptom severity, as assessed by the MGH ATRQ administered by remote, independent raters. An adequate trial is defined as an antidepressant treatment for at least 6 weeks duration at least at a minimum dose as specified in the MGH ATRQ.
- •Patients must have a HAM-D17 ≥ 18 at the end of the screening phase to qualify for inclusion. The HAM-D17 will be administered by the study clinicians at the screening and baseline visits, and by remote, independent raters during the screening phase at the time of the SAFER interview.
- •Patients must be able to be reliably rated on the psychiatric scales required by the protocol.
- •Men and women, ages 18 to 65 Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized.
- •WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea ³ 12 consecutive months; or women on hormone replacement therapy \[HRT\] with documented serum follicle stimulating hormone \[FSH\] level \> 35 mIU/mL). Even women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential.
- •WOCBP must have a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product.
- •Meet DSM-IV criteria (by Structured Clinical Interview for DSM-IV - SCID-I/P) for MDD, current;
Exclusion Criteria
- •WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period \[and for up to 4 weeks after the last dose of investigational product\].
- •WOCBP using a prohibited contraceptive method.
- •Women who are pregnant or breastfeeding.
- •Women with a positive pregnancy test on enrollment or prior to investigational product administration.
- •Sexually active fertile men not using effective birth control if their partners are WOCBP.
- •Patients who report an inadequate response (less than 50% decrease in depressive symptom severity) to more than two adequate trials of antidepressant treatments during the current depressive episode (including monotherapy treatment and distinct combination regimens) at a therapeutic dose (as defined by the ATRQ) and for an adequate duration (minimum six weeks for any monotherapy).
- •Patients who report treatment with adjunctive antipsychotic medication with an antidepressant for a minimum of two weeks during the current depressive episode.
- •Patients with a current need for involuntary commitment or who have been hospitalized within four weeks of the Screening Visit for the current major depressive episode.
- •Patients who have received ECT during the current episode.
- •Patients who have a current Axis I diagnosis of:
Arms & Interventions
Drug 2mg/Drug 5mg
patients randomly assigned to the drug/drug sequence, the dose of aripiprazole will be 2 mg/day during the first phase of the study, and 5 mg/day in the second phase.
Intervention: Aripiprazole 5mg
Drug 2mg/Drug 5mg
patients randomly assigned to the drug/drug sequence, the dose of aripiprazole will be 2 mg/day during the first phase of the study, and 5 mg/day in the second phase.
Intervention: Aripiprazole 2mg
Placebo/Drug 2mg
For patients randomly assigned to the placebo/drug sequence, the dose of aripiprazole will be 2 mg/day during the second phase of the study.
Intervention: Aripiprazole 2mg
Placebo/Drug 2mg
For patients randomly assigned to the placebo/drug sequence, the dose of aripiprazole will be 2 mg/day during the second phase of the study.
Intervention: Placebo
Placebo/Placebo
for patients randomly assigned to the placebo/placebo sequence, study medication will be placebo during both phases of the study.
Intervention: Placebo
Outcomes
Primary Outcomes
MADRS (Montgomery-Asberg Depression Rating Scale) Response Rate
Time Frame: 12 weeks
The primary outcome was the difference in response rate (decrease in MADRS total score of at least 50%) using the SPCD (sequential parallel comparison design). The 10-item Montgomery-Asberg Depression Rating Scale (MADRS), which measures depression severity over the past week, was completed by clinicians using an MGH structured interview. Each item is measured on a scale from 0 to 6, and the items are summed to find the total score. The total minimum score is 0 units on a scale and the total maximum score is 60 units on a scale, where higher scores indicate more severe depression.
Secondary Outcomes
- MADRS (Montgomery-Asberg Depression Rating Scale) Readmission Rate(12 weeks)
- Mean Change in MADRS (Montgomery-Asberg Depression Rating Scale) Score From Baseline to the End of Follow-up(Baseline and 12 Weeks)
- Mean Change in Clinical Global Impression of Severity (CGI-S)(Baseline and 12 weeks)
- Mean Change in Symptom Questionnaire (SQ)(Baseline and 12 weeks)