Major Depressive Disorder
Conditions
Keywords
depression, depressive, major, aripiprazole, switching, augmentation, antidepressant
Brief summary
The objective of this study is to compare the efficacy and safety of aripiprazole as adjunctive therapy versus switching to different class of antidepressants for treating major depressive disorder partially or minimally responsive to ongoing antidepressant treatment.
Detailed description
Most guidelines have suggested that those nonresponders or partial responders should be considered for a switch, combination or augmentation of treatment. Traditional augmentation agents, lithium, triiodothyronine (T3), buspirone, dopamine agonists, and stimulants have been commonly used for this patient population with limited supporting data. Recently, augmentation of atypical antipsychotics with antidepressant therapy has become a more commonly accepted treatment practice. This strategy has proven to be useful for enhancement of antidepressant effect, showing increased remission rates and early treatment effects on core depressive symptoms, and comorbid symptoms as well as antidepressant- mediated side effects (e.g., sexual dysfunction). Although, we have some limited treatment options to treat such patients as described above, it is not clear which treatment option would be best or acceptable for those patients in clinical practice yet. Among above augmentation agents, aripiprazole is the first drug approved by U.S. FDA. as an augmentation therapy to antidepressants in the treatment of patients with MDD showing imminent efficacy and reliable safety profile through adequately-powered well-designed controlled clinical trials.
Interventions
DRUGAripiprazole
patients who are randomly assigned to adjunctive aripiprazole are treated with a starting dose of 2.5 (or 5) mg/day of aripiprazole, which can be increased weekly in 2.5\ 5mg/day increments to a maximum dose of 15 mg/day based on assessment of tolerability and clinical response. Doses can be decreased at any visit, based on tolerability; They continue to receive the same fixed-dose of the previously used antidepressant throughout the study period when patient is assigned to aripiprazole augmentation group.
DRUGswitching to different class of antidepressant
Patients randomly assigned to switching to different antidepressant have to discontinue the previously used antidepressant and receive different antidepressant within flexible therapeutic doses as indication label information (as based on clinicians' preference and experience). Dose increase is permitted until the first 2 weeks of the study.
Sponsors
Korea OIAA
Taiwan Otsuka Pharm. Co., Ltd
Korea University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who are older than 20 years of age have a diagnosis of MDD without psychotic features, as defined by DSM-IV-TR. * Patients have to report an inadequate response to a current antidepressant treatment. Inadequate response to antidepressant is defined as: total score of HDRS-17 is more than 14), despite adequate dose of current antidepressant treatment for at least 6 weeks in the current episode(co-administered with ATRQ) * Classification of antidepressants which can be included in the study(list for suggestion): Escitalopram 10\ 20mg/day, fluoxetine 20\ 40mg/day,paroxetine controlled release(CR) 25\ 62.5mg or paroxetine 20\ 40mg, sertraline 100\ 150mg,bupropion XL(SR) 150\ 300mg, mirtazapine 15\ 45mg,venlafaxine immediate or extended release(IR or ER) 112.5\ 225mg/day, duloxetine 60mg \[same criteria for generic medications as brand drugs\]
Exclusion criteria
* Those who are first episode, drug naive MDD subjects * Those who have a current Axis I diagnosis of delirium, dementia, amnestic or other cognitive disorder, schizophrenia or other psychotic disorder, bipolar 1 or 2 disorder, eating disorder, obsessive-compulsive disorder, panic disorder, or posttraumatic stress disorder * Those who have a clinically significant current Axis 2 diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal, or histrionic personality disorder * Those who experience hallucinations, delusion, or any psychotic symptomatology in the current depressive episode * Those who have met DSM-IV-TR criteria for any significant substance use disorder within the past 12 months (except nicotine) * Those who have known allergy,hypersensitivity or previous unresponsiveness to aripiprazole or known intolerance to other study medications * Those who have had cognitive-behavioral therapy or other psychotherapy, or they have the potential need to be treated with them during the study periods * Those who are complicated with serious medical problem, such as severe renal, hepatic dysfunction, cardiovascular, lung, gastrointestinal, endocrine, nervous, infectious disease, or neoblastic, metabolic disease * Those who have shown previous unresponsiveness to adequate antidepressant trials more than 2 episodes or with 3 or more antidepressant treatments * Those who have chronic liver or renal disease * Those who are pregnant or brest-feeding * Those who have participated in a clinical trial with aripiprazole or any other investigational product within the past month(include randomized, double-blind, placebo-controlled or open-label study; but chart review,observational study can be enrolled) * Those who had a history of thyroid pathology, neuroleptic malignant syndrome, or serotonin syndrome * Those who have received adjunctive antipsychotic plus antidepressant for more than 3 weeks during the current episode * Those who have received electroconvulsive therapy for the current episode * Those who have shown an inadequate response to previous ECT in any episode * Those who have a suicidal risk * Those who are likely to require prohibited concomitant therapy during the trial * Those who have received treatment with a monoamine oxidase inhibitor within 2 weeks prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of total score of MADRS | From baseline to end of treatment | MADRS: montgomery Asberg Depression Rating Scale |
| Response rate | at 2 weeks | response rate is defined as a reduction in MADRS total score of at least 50% relative to the beginning of the randomized phase (baseline) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of total score of HDRS-17 | from baseline to end of treatment | HDRS-17: Hamilton Depression Rating Scale-17 item |
| Change of total score of CGI-S | from baseline to end of treatment | CGI-S: Clinical Global Impression-Severity Score |
| Response rate | at week 2,4 and 6 | — |
| Change of total score of SDS | from baseline to end of treatment | SDS: Sheehan Disability Scale |
| Patients' ratio who have have scored 1 or 2 in the score of CGI-Improvement | at the end of treatment | CGI-I: Clinical Global Impression-Improvement Score |
| Change of total score of IFS | from baseline to end of treatment | IFS: Iowa Fatigue Scale |
| Remission rate | at week 2,4and 6 | remission rate is defined as an absolute MADRS total score of ≤10 at the end of treatment |
Countries
South Korea, Taiwan
Outcome results
None listed