Switching to Duloxetine in Patients With Depression

Study Overview
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Brief Summary
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The purpose of this study is to help answer the following research question: Whether switching to duloxetine improves depressed mood when current treatment did not work well for patients with depression.

Official Title
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Attributes of Response in Depressed Patients Switched to Treatment With Duloxetine (ARDENT Study)

Conditions
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Depressive Disorder, Major

Intervention / Treatment
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* Drug: Duloxetine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female outpatients aged 18 years or older who meet criteria for Major Depressive Disorder (MDD). Currently receiving a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) class of antidepressant for at least a month for the treatment of depression. Females of child-bearing potential (not surgically sterilized and between menarche and 1 year postmenopause) to test negative for pregnancy based on a urine pregnancy test and to agree to use a reliable method of birth control. Exclusion Criteria: Women who are pregnant or plan to be pregnant or are breastfeeding. To have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication. Diagnosed with treatment resistant depression. History of bipolar disorder, schizophrenia, or other psychotic disorders. To have previously taken duloxetine that didn't work. Judged to be at serious suicidal risk in the opinion of the investigator and/or score >=3 on Item 3 (suicide) of the 17-Item Hamilton Depression Rating Scale (HAMD-17) at screening (Visit 1) or baseline (Visit 2). A serious medical illness that may need treatment during the study. Taking certain medications that are not allowed in this study. To have a history of alcohol and/or drug abuse or dependence within the past year. To have uncontrolled narrow-angle glaucoma. To have allergic reactions to many medicines. To have undergone shock therapy (Electroconvulsive Therapy) or magnet treatment (Transcranial Magnetic Stimulation) within the past year. To initiate talk therapy (psychotherapy) just before or during the study. To have chronic pain and you have been taking medicine for it for the last 6 months. To have certain liver diseases. To have kidney disease or undergoing dialysis. Abnormal thyroid stimulating hormone (TSH) concentration.

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
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duloxetine<br>Patients who met criteria in Study Period I (screening) were treated with duloxetine 60 milligrams (mg) once daily (QD) in an open-label manner for 4 weeks (Study Period II). Study Period II was considered the acute therapy period. Study Period III was a 4-week interval where patients who did not respond during Study Period II had their duloxetine doses optimized to 120 mg. | Drug: Duloxetine<br>* Study Period II (Acute Therapy): 60 mg capsules, QD, for 4 weeks. Study Period III (Optimization): Responder group - 60 mg capsules, QD, for 4 weeks more. Non-responder group - 120 mg capsules, QD, for 4 weeks more.<br>* Other names: Cymbalta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Brief Pain Inventory-Modified Short Form (BPI-SF) Interference Score Between Responder and Non-Responder Participants at 4 Weeks | BPI-SF interference score asks about the degree to which pain interferes with mood, walking and other physical activity, work, social activity, relations with others, and sleep. BPI-SF interference score ranges from 0 (no interference) to 10 (interferes completely). Response is defined as a >=50% reduction in the Maier subscale score from baseline. The Maier subscale (Items 1,2,7,8,9,10) represents core symptoms of depression. Total subscale scores range from 0 (normal) to 24 (severe). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. | Baseline, 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Meeting Criteria for Response on the 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale at 4 and 8 Weeks | The Maier subscale (Items 1,2,7,8,9,10) represents the core symptoms of depression. Total subscale scores range from 0 (normal) to 24 (severe). Response is defined as a >=50% reduction in the Maier subscale score from baseline. | Baseline, 4 weeks, 8 weeks | 
| Change From Baseline HAMD-17 Total Score at 8 Weeks | The HAMD-17 total score measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. | Baseline, 8 weeks | 
| Change From Baseline HAMD-17 Core Subscale at 8 Weeks | The Core subscale (Items 1,2,3,7,8) evaluates core symptoms of depression. Total subscale scores range from 0 (normal) to 20 (severe). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. | Baseline, 8 weeks | 
| Change From Baseline HAMD-17 Maier Subscale at 8 Weeks | The Maier subscale (Items 1,2,7,8,9,10) represents the core symptoms of depression. Total subscale scores range from 0 (normal) to 24 (severe). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. | Baseline, 8 weeks | 
| Change From Baseline HAMD-17 Anxiety/Somatization Subscale at 8 Weeks | The Anxiety/Somatization Subscale (Items 10-13, 15, 17) evaluates severity of psychic and somatic manifistations of anxiety as well as agitation. Total subscale scores range from 0 (normal) to 18 (severe). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. | Baseline, 8 weeks | 
| Change From Baseline HAMD-17 Retardation/Somatization Subscale at 8 Weeks | The Retardation Subscale (Items 1,7,8,14) evaluates dysfunction in mood, work, and sexual activity, as well as overall motor retardation. Total subscale scores range from 0 (normal) to 14 (severe). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. | Baseline, 8 weeks | 
| Change From Baseline HAMD-17 Sleep Subscale at 8 Weeks | The Sleep Subscale (Items 4,5,6) evaluates initial, middle, and late insomnia. Total subscale scores range from 0 (no difficulty) to 6 (difficulty). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. | Baseline, 8 weeks | 
| Change From Baseline in the Hamilton Anxiety Rating Scale (HAMA) at 8 Weeks | The HAMA scale measures anxiety symptoms accompanying major depressive disorder (MDD). Each item of the 14-item HAMA was scored from 0 (not present) to 4 (very severe), with a resulting maximum total score of 56. Factors used for adjustment for least squares means are listed in 'Other relevant information' section. | Baseline, 8 weeks | 
| Change From Baseline in the Clinical Global Impression - Severity (CGI-Severity) Scale at 8 Weeks | Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. | Baseline, 8 weeks | 
| Change From Baseline in the Brief Pain Inventory - Modified Short Form (BPI-SF) Average Pain Score at 8 Weeks | A self-reported scale that measures the severity of pain based on the average pain experienced over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. | Baseline, 8 weeks | 
| Change From Baseline in Patient Global Impression - Improvement (PGI-I) Scale Score at 8 Weeks | A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. | 8 weeks | 
| Change From Baseline in the Sexual Functioning Questionnaire Clinical Version (CSFQ) at 4 and 8 Weeks | A 14-item patient-rated scale assesses medication-related changes in sexual activity/functioning. Items rated from 1 (never, low enjoyment/pleasure) to 5 (every day, great enjoyment/pleasure). CSFQ measures 5 dimensions of sexual behavior: pleasure; desire/frequency; desire/interest; arousal; orgasm. Lower total scores are associated with diminished sexual functioning. Total scores <=47 (men) and <=41 (women) indicate global sexual dysfunction, with all phases of sexual response cycle affected. Factors used for adjustment for least squares means are in 'Other relevant information' section. | Baseline, 4 Weeks, 8 weeks | 
| Change From Baseline in the Treatment Satisfaction Questionnaire for Medication (TSQM) at 4 and 8 Weeks | The TSQM is a participant-reported measure that best describes how the study medication makes them feel since the last study visit, assessing perceived effectiveness, severity of side effects, and convenience. Convenience, Effectiveness, Side-Effects, and Global Satisfaction scale scores range from 0 (extremely dissatisfied) to 100 (extremely satisfied). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. | Baseline, 4 weeks, 8 weeks | 
| Change From Baseline in the Sheehan Disability Scale (SDS) at 4 and 8 Weeks | The SDS is completed by the patient and is used to assess the effect of the patient's symptoms on their work/social/family life. Total scores range from 0 to 30 with higher values indicating greater disruption in the patient's work/social/family life. Factors used for adjustment for least squares means are listed in 'Other relevant information' section. | Baseline, 4 weeks, 8 weeks |