Study of Aripiprazole as an Adjunctive Therapy in Patients With Major Depressive Disorder

Study Overview
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Brief Summary
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To examine the efficacy and safety of aripiprazole versus placebo as an adjunctive therapy co-administered with either an selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) in patients with major depressive disorder.

Official Title
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Placebo-Controlled, Double-Blind, Parallel Group-Comparison Study of Aripiprazole as an Adjunctive Therapy in Patients With Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Aripiprazole (Fixed dose)
* Drug: Aripiprazole (Titrated dose)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are either inpatients or outpatients Patients who have the ability to understand and to provide informed consent to the examination, observation, and evaluation processes specified in this protocol, and have signed the informed consent form based on a full understanding of the trial Patients diagnosed as having either 296.2x Major Depressive Disorder, Single Episode or 296.3x Major Depressive Disorder, Recurrent according to DSM-IV-TR, and for whom the current episode of major depressive disorder has been ongoing for more than 8 weeks Patients with a HAM-D17 total score of 18 or more Exclusion Criteria: Female patients of child bearing potential who wish to become pregnant during the treatment period, or within 4 weeks after study completion/discontinuation Female patients who are pregnant, possibly pregnant, or breast feeding Patients judged to be unable to tolerate any type of antidpressant treatment (including drugs not being used in the current episode of major depressive disorder), based on treatment history to date Patients who have previously received electro-convulsive therapy Patients who have participated in clinical studies on medical devices or other drugs within the past month Patients at risk of having serious adverse events or developing symptoms that could interfere with safety and efficacy evaluations (such as symptoms of fibromyalgia syndrome overlapping with symptoms of depression), based on previous medical history Patients with a history or a complication of diabetes Patients with thyroid disease (excluding patients who are stabilized on drug therapy for at least 3 months) Patients with a history of serotonin syndrome or psychotropic neuroleptic malignant syndrome Patients with a history of seizure disorder (epilepsy etc.)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Fixed dose | Drug: Aripiprazole (Fixed dose)<br>* administered orally once daily, 3 mg daily, 6 weeks<br>* Other names: Aripiprazole;|
| Experimental: 2<br>Titration dose | Drug: Aripiprazole (Titrated dose)<br>* administered orally once daily, 3 to 15 mg daily, 6 weeks<br>* Other names: Aripiprazole;|
| Placebo Comparator: 3<br>Placebo | Drug: Placebo<br>* administered orally once daily, 6 weeks<br>* Other names: Placebo of aripiprazole;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | The change in MADRS total score from the end of the SSRI/SNRI treatment period to Week 6 of the placebo-controlled, double-blind treatment period by covariance analysis, and compared the aripiprazole variable dose group with the placebo group as well as the aripiprazole fixed dose group with the placebo group. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The questionnaire includes questions on the following symptoms 1. Apparent sadness 2. Reported sadness 3. Inner tension 4. Reduced sleep 5. Reduced appetite 6. Concentration difficulties 7. Lassitude 8. Inability to feel 9. Pessimistic thoughts 10. Suicidal thoughts | Baseline (the end of the SSRI/SNRI treatment period), at completion of administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MADRS Response Rate | The percentage of subjects with a decrease in MADRS total score of 50% or more, from the end of the SSRI/SNRI treatment period to the end of the placebo-controlled, double-blind treatment period (or withdrawal). | Baseline (the end of the SSRI/SNRI treatment period), at completion of administration | 
| Mean Change in Sheehan Disability Scale (SDISS) | The endpoint evaluated the change in SDISS from the end of the SSRI/SNRI treatment period to Week 6 of the placebo-controlled, double-blind treatment period. The patient rates the extent to which his or her 1) work, 2) social life or leisure activities, and 3) home life or family responsibilities are impaired by his or her symptoms on a 10-point visual analog scale. The three items may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired). | Baseline (the end of the SSRI/SNRI treatment period), at completion of administration |