A Study Comparing Duloxetine to Other Antidepressants in the Treatment of Severe Depression

Study Overview
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Brief Summary
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The purpose of this study is to compare duloxetine with other antidepressants in the treatment of severe depression.

Official Title
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TRY FIRST: A 12-Week, Randomized, Open-Label Trial of Duloxetine Versus Generic SSRIs in the Treatment of a Severe Depressive Episode

Conditions
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Depression

Intervention / Treatment
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* Drug: duloxetine
* Drug: fluoxetine
* Drug: citalopram
* Drug: paroxetine
* Drug: sertraline


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: At least 18 years of age Have major depression and are currently in a severe depressive episode Have a degree of understanding such that patient can communicate with the investigator and study staff All females must test negative for pregnancy Females of childbearing potential must use reliable method of birth control during the study and for 1 month after taking the last dose of study drug Exclusion criteria: Have not responded to duloxetine for depression in the past Have a history of bipolar disorder, a psychotic disorder (such as schizophrenia), a cognitive disorder (such as moderate or severe dementia), or obsessive-compulsive disorder (OCD) Are at significant risk for suicide Have not responded to 2 or more adequate trials of antidepressant medications during the current depressive episode Have a serious, unstable medical condition Have a current or recent history of substance abuse or dependence Have had electroconvulsive therapy (ECT), transcranial magnetic stimulation (rTMS), or vagus nerve stimulation (VNS) in the past year Have started psychotherapy within 6 weeks prior to study entry Have a serious medical illness or clinically significant laboratory abnormality that is not stabilized or is anticipated, in the judgment of the investigator, to require hospitalization or use of an excluded medication during the course of the study

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: duloxetine<br>study drug | Drug: duloxetine<br>* 30-120 milligrams (mgs) orally daily for 12 weeks<br>* Other names: Cymbalta;|
| Active Comparator: citalopram<br> | Drug: citalopram<br>* 20-40 mgs orally daily for 12 weeks<br>|
| Active Comparator: fluoxetine<br> | Drug: fluoxetine<br>* 20-80 mgs orally daily for 12 weeks<br>|
| Active Comparator: paroxetine<br> | Drug: paroxetine<br>* 20-50 mgs orally daily for 12 weeks<br>|
| Active Comparator: sertraline<br> | Drug: sertraline<br>* 50-200 mgs orally daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probability of Remission [16-item Quick Inventory of Depressive Symptomatology (QIDS-SR) Score Less Than or Equal to 5 at 12-Week Endpoint] | Visitwise probability of participants per treatment meeting remission criteria (QIDS-SR total score [TS]</=5 at week 12 endpoint) were estimated using a pseudolikelihood-based mixed-models repeated measures analysis for a categorical outcome, model included fixed, categorical effects of treatment group (duloxetine vs. SSRIs), visit, treatment group-by-visit & continuous, fixed covariate of baseline QIDS-SR TS, and random effect of participant. Primary analysis contrasted remission probability at week 12 endpoint between treatment groups. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in QIDS-SR Total Score at 12-Week Endpoint (Mood Measure) | The QIDS-SR is a 16-item, participant-rated short form of the Inventory of Depressive Symptomatology that assesses 9 domains: sad mood, concentration, self-outlook, suicidal ideation, involvement, energy/fatigability, sleep disturbance, appetite/weight increase/decrease and psychomotor agitation/retardation. Scores range from 0 (none) to 27 (very severe). The QIDS-SR total score was used to derive the mean change from baseline to endpoint depression. | Baseline, 12 weeks | 
| Probability of Remission [17-item Hamilton Depression Rating Scale (HAMD-17) (Mood Measure) Less Than or Equal to 7 at 12-Week Endpoint] | Visitwise percentages of participants meeting remission criteria HAMD-17 total score [TS] </=7 at week 12 endpoint) were estimated using a categorical, pseudolike-lihood-based repeated measures approach, & included fixed, categorical effects of treatment group (duloxetine vs. SSRIs), visit, treatment group-by-visit interaction, & continuous, fixed covariate of baseline HAMD-17 TS. Primary analysis will be contrast of remission rates at week 12 endpoint between treatment groups, & represents estimated remission rates for each treatment group had all participants completed 12 weeks of therapy. | 12 weeks | 
| Probability of Response [QIDS-SR Total Score (Mood Measure) Greater Than Or Equal To 50 Percent Reduction From Baseline To 12 Week Endpoint] | Visitwise percentages of participants meeting response criteria (50% reduction from baseline QIDS-SR total score at 12-week endpoint) were estimated using a categorical, pseudolikelihood-based repeated measures approach, & included fixed, categorical effects of treatment group, visit, treatment group-by-visit interaction, & continuous, fixed covariate of baseline QIDS-SR. The primary analysis will be the contrast of response rates at week 12 endpoint between treatment groups, and represents estimated response rates for each treatment group had all participants completed 12 weeks of therapy. | Baseline, 12-Weeks | 
| Probability of Response [HAMD-17 Total Score (Mood Measure) Greater Than Or Equal To 50 Percent Reduction From Baseline To 12 Week Endpoint] | Visitwise percentages of participants meeting response criteria 50% reduction from baseline in HAMD-17 total score at 12-Week endpoint) were estimated using a categorical, pseudolike-lihood-based repeated measures approach, & included fixed, categorical effects of treatment group, visit, treatment group-by-visit interaction, & continuous, fixed covariate of baseline HAMD-17 TS. Primary analysis will be the contrast of response rates at week 12 endpoint between treatment groups, & represents estimated response rates for each treatment group had all participants completed 12 weeks of therapy. | Baseline, 12-Weeks | 
| Change From Baseline in HAMD-17 Total Score at 12-Week Endpoint (Mood Measure) | The HAMD-17 is a rater-administered assessment of depression severity and improvement, with total score ranges from 0 (not at all depressed) to 52 (most severely depressed). | Baseline, 12 Weeks | 
| Change From Baseline in HAMD-17 Anxiety/Somatization Subscale Score at 12-Week Endpoint (Mood Measure) | HAMD-17 subscale consists of items 10, 11, 12, 13, 15, and 17 evaluates agitation, and severity of psychic and somatic manifestations of anxiety. Total subscale scores range from 0 (normal) to 18 (severe). Mean change from baseline to endpoint. | Baseline, 12 Weeks | 
| Change From Baseline in HAMD-17 Maier Subscale Score at 12-Week Endpoint (Mood Measure) | HAMD-17 Maier Subscale consists of Items 1, 2, 7, 8, 9, 10 and represents the core symptoms of depression. Total subscale scores range from 0 (normal) to 24 (severe). | Baseline, 12 weeks | 
| Change From Baseline in HAMD-17 Bech Subscale Score at 12-Week Endpoint (Mood Measure) | HAMD-17 Bech subscale consists of items 1, 2, 7, 8, 10, and 13 used to evaluate core symptoms of Major Depressive Disorder (MDD). Total subscale scores range from 0 (normal) to 22 (severe). | Baseline, 12 Weeks | 
| Change From Baseline in HAMD-17 Retardation Subscale Score at 12-Week Endpoint (Mood Measure) | The HAMD-17 Retardation subscale consists of Items 1, 7, 8, 14 and evaluates dysfunction in mood, work, and sexual activity, as well as overall motor retardation. Total subscale scores range from 0 (normal) to 14 (severe). | Baseline, 12 Weeks | 
| Change From Baseline in HAMD-17 Sleep Subscale Score at 12-Week Endpoint (Mood Measure) | The HAMD-17 Sleep Subscale consists of Items 4, 5, 6 and evaluates initial, middle, and late insomnia. Total subscale scores range from 0 (no difficulty) to 6 (difficulty). | Baseline, 12 Weeks | 
| Change From Baseline in Brief Pain Inventory (BPI) Average 24-hour Pain Score, in Particpants With a Baseline BPI Average 24-hour Pain Score of 3 or Greater, at 12-Week Endpoint (Pain Measure) | The BPI is a self-reported scale measuring pain severity and pain-specific interference on function on a scale ranging from 0 (no pain) to 10 (pain as bad as you can imagine). The BPI average 24-hour pain measure was used to derive the overall mean change from baseline to endpoint, in those participants who had a BPI average 24-hour pain score of 3 or greater at baseline. | Baseline, 12 Weeks | 
| Change From Baseline in BPI Average 24 Hour Pain Score at 12-Week Endpoint (Pain Measure) | The BPI is a self-reported scale measuring pain severity and pain-specific interference on function, with scores ranging from 0 (does not interfere) to 10 (completely interferes). The BPI average 24-hour pain measure was used to derive the overall mean change from baseline to endpoint. | Baseline, 12 weeks | 
| Change From Baseline in Sheehan Disability Scale (SDS) Global Functional Impairment Score at 12-Week Endpoint (Functional Outcome Measure) | The SDS is a participant-rated anchored visual analog scale to assess disability across the three domains of work/school, social life, and family life, with each item scored from 0 (not at all) to 10 (very severely), with a summarization of the 3 items to evaluate global functioning. The Global Functional Impairment Score is a total score score that ranges from 0 (unimpaired) to 30 (highly impaired), and was used to derived the mean change from baseline to endpoint. | Baseline, 12 weeks | 
| Change From Baseline in SDS Work/School Item Score at 12-Week Endpoint (Functional Outcome Measure) | The SDS is completed by the participant and Item 1 is used to assess the effect of the participant's symptoms on their work/school schedule. Scores range from 0 to 10 with higher values indicating greater disruption in the participant's work/school life. | Baseline, 12 Weeks | 
| Change From Baseline in Sheehan Disability Scale (SDS) Family/Home Item Score at Week-12 Endpoint (Functional Outcome Measure) | The SDS is completed by the participant and Item 3 is used to assess the effect of the participant's symptoms on their family life/home responsibilities. Scores range from 0 to 10 with higher values indicating greater disruption in the participant's family life/home responsibilities. | Baseline, 12 Weeks | 
| Change From Baseline in SDS Social Item Score at 12-Week Endpoint (Functional Outcome Measure) | The SDS is completed by the participant and is used to assess the effect of the participant's symptoms on their work/social/family life. Total scores range from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life. | Baseline, 12 Weeks | 
| Change From Baseline in Systolic Blood Pressure at Week-12 Endpoint | Mean change from baseline to endpoint in systolic blood pressure | Baseline, 12 Weeks | 
| Change From Baseline in Diastolic Blood Pressure at Week-12 Endpoint | Mean change from baseline to endpoint in diastolic blood pressure | Baseline, 12 Weeks | 
| Change From Baseline in Pulse Rate at Week-12 Endpoint | Mean change from baseline to endpoint in pulse rate | Baseline, 12 Weeks | 
| Change From Baseline in Weight at Week-12 Endpoint | Mean change from baseline to endpoint in weight | Baseline, 12 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe Depressive Episode