A Comparison of Tolerability and Efficacy of Different Doses of Duloxetine for the Treatment of Major Depressive Disorder

Study Overview
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Brief Summary
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The purpose of this study is to compare the tolerability and efficacy of different doses of duloxetine in patients with major depressive disorder.

Official Title
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A Comparison of Duloxetine Dosing Strategies in The Treatment of Patients With Major Depression

Conditions
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Depressive Disorder

Intervention / Treatment
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* Drug: duloxetine hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients at least 18 years of age (male and/or female) who meet criteria for major depressive disorder (MDD) as defined by the Diagnostic and Statistical Manual for Mental Disorders Fourth Edition Text Revision (DSM-IV-TR). Patients may have comorbid Anxiety Disorders, except for Obsessive Compulsive Disorder Tests negative for pregnancy at the time of enrollment based on a serum pregnancy test and agrees to use a reliable method of birth control (for example, use of oral contraceptives or Norplant a reliable barrier method of birth control diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices; partner with vasectomy; or abstinence) during the study and for 1 month following the last dose of study drug. Hamilton Depression Rating 17 Item Scale (HAMD-17) greater than 15 at Visits 1 and 2. Exclusion Criteria: Have any current Axis I disorder other than major depressive disorder (MDD), dysthymia, or any anxiety disorder; however, obsessive-compulsive disorder is excluded. Have any previous or current diagnosis of bipolar disorder, obsessive-compulsive disorder, schizophrenia, or other psychotic disorders. Lack of response of the current episode of major depression to two or more adequate courses of antidepressant therapy at clinically appropriate dose for a minimum of 4 weeks or, in the judgment of the investigator, the patient meets criteria for treatment-resistant depression. DSM-IV-TR-defined history of substance abuse or dependence within the past 6 months, excluding nicotine and caffeine. Patients judged to be at serious suicidal risk in the opinion of the investigator.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: duloxetine hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective in the acute phase of this study is to compare the incidence of treatment-emergent nausea |  |  | 
| for patients initially dosed at duloxetine 30 mg QD |  |  | 
| (once-daily), versus duloxetine 60 mg QD. |  |  | 
| The primary objective in the extension phase of this study is to compare efficacy in patients not meeting response criteria during the acute phase for patients dosed at duloxetine 60 mg QD versus duloxetine 120 mg QD. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary objective of greatest importance is to compare the incidence of treatment-emergent nausea |  |  | 
| (as defined for the primary objective) for patients |  |  | 
| initially dosed at duloxetine 30 mg QD, versus duloxetine 30 mg BID (twice-daily). |  |  | 
| Additional secondary objectives include comparing the three initial dosing groups in regards to:Mean changes from baseline in the category total scores and individual items scores of the AMDP-5 |  |  | 
| The incidence and severity of adverse events using rates of spontaneously reported treatment-emergent adverse events, rates of discontinuations due to |  |  | 
| adverse events, categorical changes in AMDP-5 items, mean changes and categorical changes in vital signs |  |  | 
| as well as mean changes and rates of abnormal laboratory analytes |  |  | 
| Mean changes from baseline in the HAMD17 total score, HAMD subscales, HAMD17 individual items, 30-item Inventory of Depressive Symptoms, |  |  | 
| Clinician Rated (IDS-30) total score and individual items, Brief Pain Inventory items and interference |  |  | 
| total score, Visual Analog Scales for pain, Clinical Global Impressions of Severity (CGI-Severity), Post-baseline means |  |  | 
| on the Patient's Global Impression of Improvement (PGI-I), Remission rates (HAMD17 total score of less than 7), |  |  | 
| and response rates (greater than 50% decrease from baseline on the HAMD17 total score). |  |  | 
| - Sexual dysfunction, as measured by categorical changes (same, better, worse) and presence vs. absence, based on the patient global assessment of sexual functioning. |  |  | 
| Time to onset of action in depression (30% improvement in Maier Subscale of HAMD) and painful physical symptoms (30% improvement in as measure by the BPI interference total score). |  |  |