Antidepressant Plus Asenapine Versus Antidepressant Plus Placebo for Depression

Study Overview
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Brief Summary
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This is a 6-week comparison of asenapine versus placebo as an add-on to ongoing antidepressant treatment in patients with major depression who have not had a complete therapeutic response to treatment with the antidepressant alone. The investigators hypothesize that added asenapine will produce greater reductions in depression than will added placebo.

Detailed Description
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The investigators will undertake a 6-week, double-blind, randomized, parallel-group, placebo-controlled trial of adjunctive asenapine in 130 patients with MDD without psychosis who have had an incomplete therapeutic response to treatment with an antidepressant medication alone.

Official Title
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A Randomized, Blinded, Comparison of Asenapine and Placebo as Adjunctive Treatment in Patients With Non-Psychotic Major Depressive Disorder Incompletely Responsive to Antidepressant Monotherapy

Conditions
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Major Depressive Disorder Without Psychotic Features

Intervention / Treatment
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* Drug: Asenapine 5-20 mg daily
* Drug: Placebo 1-4 tablets daily


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -130 male or female patients, 18-65 years of age, with: DSM-IV diagnosis of MDD without psychosis (single episode or recurrent) confirmed by the Mini-International Neuro-psychiatric Interview (MINI) MADRS total score > 20, and item 1 (Apparent Sadness) score > 2 at enrollment and randomization Inadequate therapeutic response during their current depressive episode; an inadequate therapeutic response will be defined as continued depressive psychopathology (see criterion 2) following > six weeks of therapy at adequate doses (according to the US label) of any non-tricyclic, non-MAOI antidepressant medication Exclusion Criteria: Additional DSM-IV Axis I diagnoses other than Generalized Anxiety Disorder, Panic Disorder with or without Agoraphobia, or Social Phobia within 6 months prior to enrollment DSM-IV Axis II diagnoses that significantly impact the current psychiatric status Current MDD episode lasting > 12 months Electroconvulsive therapy within the preceding 6 months Substance or alcohol dependence, as defined by DSM-IV criteria, within 6 months prior to enrollment Unstable medical illness, epilepsy, traumatic brain injury, Parkinson disease, or dementia (MMSE <24) Risk of suicide as defined by MADRS item 10 score > 4 Prior failure to respond to asenapine Pregnancy or failure to use an acceptable form of birth control. Pregnancy as determined by serum pregnancy test at baseline Hepatic impairment and history of low WBC, by medical history and interview.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Asenapine 5-20 mg daily<br>Asenapine will be started at 5 mg BID. The asenapine dose can be increased to 15 mg daily and then to 20 mg daily, or reduced to 5 mg daily, depending on therapeutic response and tolerability | Drug: Asenapine 5-20 mg daily<br>* 5 mg QHS, or 5 mg BID, or 5 mg QAM and 10 mg QHS, or 10 mg BID<br>* Other names: SAPHRIS;|
| Placebo Comparator: Placebo 1-4 tablets daily<br>Matched, blinded placebo tablets will be administered at doses from 1-4 tablets daily depending on therapeutic response and tolerability | Drug: Placebo 1-4 tablets daily<br>* One placebo tablet QHS, or one placebo tablet BID, or one placebo tablet QAM and two placebo tablets QHS, or two placebo tablets BID<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in MADRS Total Score | The Montgomery Asberg Depression Rating Scale (MADRS) is used by clinicians to assess the severity of depression among patients with a diagnosis of depression. It is designed to be sensitive to change resulting from antidepressant therapy. MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms. | Baseline, 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study Completion Rate | The percentage of patients completing the study in their assigned treatment arm (asenapine or placebo) at the end of 6 weeks | 6 weeks | 
| Clinical Response Rate | Clinical Response rate will be defined as the number of participants with a > 50% reduction from baseline in MADRS total score. MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms. | Baseline, 6 weeks | 
| Clinical Remission Rate | Clinical Remission will be defined as the number of participants with a MADRS total score < 7. MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms. | 6 weeks | 
| Rates of Sustained Remission | Sustained remission will be defined as at least two consecutive post-randomization assessments (weeks 2, 4, and 6) during which minimal depressive psychopathology (MADRS < 7) is present. MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms. | 2, 4, 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Antidepressant, Antipsychotic