Duloxetine Versus Placebo in the Prevention of Recurrence of Major Depressive Disorder

Phase 3

Completed

Conditions: Depressive Disorder, Major

Interventions: Drug: Duloxetine
Drug: placebo

Registration Number: NCT00105989

Lead Sponsor: Eli Lilly and Company

Brief Summary: The purpose of this study is to assess the efficacy and safety of duloxetine compared with placebo in the prevention of depressive recurrences among patients with recurrent major depressive disorder.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 514

Inclusion Criteria

Patient must be at least 18 years old.
Patient must be diagnosed with depression and have had previous episodes of depression.
Patient must sign informed consent.

Exclusion Criteria

Female and pregnant or breastfeeding.
History of bipolar disorder, schizophrenia, or other psychotic disorders.
Suffer from a serious medical illness (other than depression) or abnormal laboratory result that would require a change in medication, intervention, or hospitalization.
Have been treated with a medication called monoamine oxidase inhibitor (MAOI) within 14 days of the start of the study, or potential need to use a MAOI within 5 days of finishing the study.
Have taken an antidepressant called fluoxetine within 30 days of the start of the study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	Duloxetine	duloxetine 60-120 mg every day (QD), by mouth (PO) for 34 weeks followed by duloxetine 60-120 mg QD, PO for up to 54 weeks
B	placebo	duloxetine 60-120 mg every day (QD), by mouth (PO) for 34 weeks followed by placebo QD, PO for up to 54 weeks

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Depressive Recurrence After Time (t) in Days	Every Visit from Week 34 up to Week 86 (Maintenance Phase)	Recurrence: Clinical Global Impression-Severity (CGI-S) score \>=4 and met Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for major depressive disorder (MDD); had 3 consecutive visits where re-emergence criteria met; had total of 10 visits where re-emergence criteria was satisfied; discontinued due to lack of efficacy.

Secondary Outcome Measures

Name	Time	Method
Recurrence Count	Every Visit from Week 35 up to Week 86 (Maintenance Phase)	Number of participants who experienced a depressive recurrence at any time during the double-blind maintenance therapy phase.
Percentage of Participants With Greater Than or Equal to 50% Worsening After Time (t) in Days	Every Visit from Week 34 up to Week 86 (Maintenance Phase)	Worsening occurs if patient had a \>=50% increase from baseline on the 17-Item Hamilton Depression Rating Scale (HAMD-17) total score and a Clinical Global Impression-Severity (CGI-S) score \>=3 at any time during the double-blind maintenance therapy phase.
Loss of Response at Any Time	Every Visit from Week 35 up to Week 86 (Maintenance Phase)	Loss of response was defined as a HAMD-17 total score \>9 and a CGI-Severity score \>2 at any one time during the double-blind maintenance phase of the study regardless of whether or not they subsequently regained response or not.
Change From Baseline to Endpoint in 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score - Acute and Continuation Phases	Week 0 and Week 10 (Acute) and Week 34 (Continuation)	The 17-item HAMD 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).
Change From Baseline to Endpoint in 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score - Maintenance Phase	Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase)	The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (absent, mild, moderate, severe, very severe) or a 3-point scale (absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).
Change From Baseline to Endpoint in Clinical Global Impressions (CGI) Severity Scale - Acute and Continuation Phases	Week 0 and Week 10 (Acute) and Week 34 (Continuation)	Measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Change From Baseline to Endpoint in Clinical Global Impressions (CGI) Severity Scale - Maintenance Phase	Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase)	Measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients.
Mean Values at Endpoint in Patient's Global Impressions of Improvement (PGI-I) - Acute and Continuation Phases	Week 10 (Acute) and Week 34 (Continuation)	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).
Mean Values at Endpoint in Patient's Global Impressions of Improvement (PGI-I) - Maintenance Phase	Week 86 (Maintenance Phase)	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).
Change From Baseline to Endpoint in Hamilton Depression Rating Scale Subscales, Including the Core, Maier, Anxiety/Somatization, Retardation/Somatization, and Sleep Subscales, and the Depressed Mood Item - Acute and Continuation Phases	Week 0 and Week 10 (Acute) and Week 34 (Continuation)	Core and Maier subscales assess symptoms of depression (scores:0-20=Core; 0-24=Maier). Higher numbers indicate more severe symptoms. Anxiety/Somatization subscale assesses severity of anxiety (0-18). Retardation subscale assesses dysfunction in mood and work (0-14). Sleep subscale assesses insomnia (0-6). Depressed Mood Item (0-4).
Change From Baseline to Endpoint in Hamilton Depression Rating Scale Subscales, Including the Core, Maier, Anxiety/Somatization, Retardation/Somatization, and Sleep Subscales, and the Depressed Mood Item - Maintenance Phase	Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase)	Core and Maier subscales assess symptoms of depression (scores:0-20=Core; 0-24=Maier). Higher numbers indicate more severe symptoms. Anxiety/Somatization subscale assesses severity of anxiety (0-18). Retardation subscale assesses dysfunction in mood and work (0-14). Sleep subscale assesses insomnia (0-6). Depressed Mood item (0-4).
Change From Baseline to Endpoint in Visual Analog Scales (VAS) for Pain - Acute and Continuation Phase	Week 0 and Week 10 (Acute) and Week 34 (Continuation)	VAS for pain consists of 6 questions that assess overall pain, headache, back pain, shoulder pain, pain interference with daily activities, and pain while awake. Participant rates pain on a 100 millimeter (mm) line between two anchors (0 = no pain and 100 = very severe pain).
Change From Baseline to Endpoint in Visual Analog Scales (VAS) for Pain - Maintenance Phase	Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase)	VAS for pain consists of 6 questions that assess overall pain, headache, back pain, shoulder pain, pain interference with daily activities, and pain while awake. Participant rates pain on a 100 millimeter (mm) line between two anchors (0 = no pain and 100 = very severe pain).
Change From Baseline to Endpoint in Symptom Questionnaire-Somatic Subscale (SQ-SS) - Acute and Continuation Phases	Week 0 and Week 10 (Acute) and Week 34 (Continuation)	The Somatic subscale consists of 23 items to be completed by the patient that focus on somatic symptoms. Question answers are either yes/no or true/false. Negative response is scored at 1; positive response is scored as 0. Total Somatic subscale scores range from 0-23, where higher scores indicate greater symptom severity.
Change From Baseline to Endpoint in Symptom Questionnaire-Somatic Subscale (SQ-SS) - Maintenance Phase	Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase)	The Somatic subscale consists of 23 items to be completed by the patient that focus on somatic symptoms. Question answers are either yes/no or true/false. Negative response is scored at 1; positive response is scored as 0. Total Somatic subscale scores range from 0-23, where higher scores indicate greater symptom severity.
Change From Baseline to Endpoint in Sheehan Disability Scale (SDS) - Acute and Continuation Phases	Week 0 and Week 10 (Acute) and Week 34 (Continuation)	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 (Global) scores range from 0 to 30 with higher values indicating greater disruption in the patient's work/social/family life. Individual Item scores range from 0 to 10.
Change From Baseline to Endpoint in Sheehan Disability Scale (SDS) - Maintenance Phase	Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase)	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 (Global) scores range from 0 to 30 with higher values indicating greater disruption in the patient's work/social/family life. Individual Item scores range from 0 to 10.
Change From Baseline to Endpoint in 36-item Short-Form Health Survey (SF-36) - Acute and Continuation Phase	Week 0 and Week 10 (Acute) and Week 34 (Continuation)	Assesses general quality of life. 36 questions covering 8 health domains. Each subscale is scored by summing the individual items and transforming scores into a 0-100 scale, with higher scores indicating better health status or functioning.
Change From Baseline to Endpoint in 36-item Short-Form Health Survey (SF-36) - Maintenance Phase	Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase)	Assesses general quality of life. 36 questions covering 8 health domains. Each subscale is scored by summing the individual items and transforming scores into a 0-100 scale, with higher scores indicating better health status or functioning.
Resource Utilization and Hospitalization Module - Visits to Health Care Providers - Acute and Continuation Phases	Week 0 through Week10 (Acute) through Week 34 (Continuation)	Measures direct and indirect costs. Direct costs include inpatient and outpatient costs, while indirect costs include lost days of work and caregiver time spent with patients. Patients self-report on number of days over the past month that they have been either late to work, missed work, or missed usual activities due to symptoms.
Resource Utilization and Hospitalization Module - Visits to Health Care Providers - Maintenance Phase	Week 34 through Week 86 (Maintenance Phase)	Measures direct and indirect costs. Direct costs include inpatient and outpatient costs, while indirect costs include lost days of work and caregiver time spent with patients. Patients self-report on number of days over the past month that they have been either late to work, missed work, or missed usual activities due to symptoms.
Resource Utilization and Hospitalization Module - Change From Baseline to Endpoint in Average Number of Hours Worked in a Week - Acute and Continuation Phases	Week 0 and Week 10 (Acute) and Week 34 (Continuation)	Measures direct and indirect costs. Direct costs include inpatient and outpatient costs, while indirect costs include lost days of work and caregiver time spent with patients. Patients self-report on number of days over the past month that they have been either late to work, missed work, or missed usual activities due to symptoms.
Resource Utilization and Hospitalization Module - Change From Baseline to Endpoint in Average Number of Hours Worked in a Week - Maintenance Phase	Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase)	Measures direct and indirect costs. Direct costs include inpatient and outpatient costs, while indirect costs include lost days of work and caregiver time spent with patients. Patients self-report on number of days over the past month that they have been either late to work, missed work, or missed usual activities due to symptoms.
Resource Utilization and Hospitalization Module - Change From Baseline to Endpoint in Number of Missed Paid Work Hours - Acute and Continuation Phase	Week 0 and Week 10 (Acute) and Week 34 (Continuation)	Measures direct and indirect costs. Direct costs include inpatient and outpatient costs, while indirect costs include lost days of work and caregiver time spent with patients. Patients self-report on number of days over the past month that they have been either late to work, missed work, or missed usual activities due to symptoms.
Resource Utilization and Hospitalization Module - Change From Baseline to Endpoint in Number of Missed Paid Work Hours - Maintenance Phase	Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase)	Measures direct and indirect costs. Direct costs include inpatient and outpatient costs, while indirect costs include lost days of work and caregiver time spent with patients. Patients self-report on number of days over the past month that they have been either late to work, missed work, or missed usual activities due to symptoms.
Change From Baseline to Endpoint in Arizona Sexual Experience Scale (ASEX) - Acute and Continuation Phases (Males)	Week 0 and Week 10 (Acute) and Week 34 (Continuation)	A 5-item patient-rated scale measuring 5 domains: sexual drive, arousal (subjective excitement), lubrication/erection (physiological excitement), ability to reach orgasm, orgasm satisfaction. Higher score means worse dysfunction. Total score range is 5-30.
Change From Baseline to Endpoint in Arizona Sexual Experience Scale (ASEX) - Acute and Continuation Phases (Females)	Week 0 and Week 10 (Acute) and Week 34 (Continuation)	A 5-item patient-rated scale measuring 5 domains: sexual drive, arousal (subjective excitement), lubrication/erection (physiological excitement), ability to reach orgasm, orgasm satisfaction. Higher score means worse dysfunction. Total score range is 5-30.
Change From Baseline to Endpoint in Arizona Sexual Experience Scale (ASEX) - Maintenance Phase (Males)	Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase)	A 5-item patient-rated scale measuring 5 domains: sexual drive, arousal (subjective excitement), lubrication/erection (physiological excitement), ability to reach orgasm, orgasm satisfaction. Higher score means worse dysfunction. Total score range is 5-30.
Change From Baseline to Endpoint in Arizona Sexual Experience Scale (ASEX) - Maintenance Phase (Females)	Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase)	A 5-item patient-rated scale measuring 5 domains: sexual drive, arousal (subjective excitement), lubrication/erection (physiological excitement), ability to reach orgasm, orgasm satisfaction. Higher score means worse dysfunction. Total score range is 5-30.
Vital Signs - Change From Baseline to Endpoint in Weight - Acute and Continuation Phases	Week 0 and Week 10 (Acute) and Week 34 (Continuation)
Vital Signs - Change From Baseline to Endpoint in Weight - Maintenance Phase	Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase)
Vital Signs - Change From Baseline to Endpoint in Pulse - Acute and Continuation Phases	Week 0 and Week 10 (Acute) and Week 34 (Continuation)
Vital Signs - Change From Baseline to Endpoint in Pulse - Maintenance Phase	Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase)
Vital Signs - Change From Baseline to Endpoint in Blood Pressure - Acute and Continuation Phases	Week 0 and Week 10 (Acute) and Week 34 (Continuation)
Vital Signs - Change From Baseline to Endpoint in Blood Pressure - Maintenance Phase	Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Albumin - Acute Phase	Week 0 and Week 10
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Calcium - Acute Phase	Week 0 and Week 10
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Chloride - Acute Phase	Week 0 and Week 10
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Eosinophils - Acute Phase	Week 0 and Week 10
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Gamma-Glutamyl Transferase - Acute Phase	Week 0 and Week 10
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Hematocrit - Acute Phase	Week 0 and Week 10
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Hemoglobin - Acute Phase	Week 0 and Week 10
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Platelet Count - Acute Phase	Week 0 and Week 10
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Sodium - Acute Phase	Week 0 and Week 10
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Total Protein - Acute Phase	Week 0 and Week 10
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Uric Acid - Acute Phase	Week 0 and Week 10
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Albumin - Continuation Phase	Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Bicarbonate, HCO3 - Continuation Phase	Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Bilirubin, Direct - Continuation Phase	Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Bilirubin, Total - Continuation Phase	Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Calcium - Continuation Phase	Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Erythrocyte Count - Continuation Phase	Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Gamma-Glutamyl Transferase - Continuation Phase	Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Hematocrit - Continuation Phase	Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Hemoglobin - Continuation Phase	Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Leukocyte Count - Continuation Phase	Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Low Density Lipoprotein (LDL) Cholesterol (Direct) - Continuation Phase	Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Mean Cell Hemoglobin - Continuation Phase	Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Mean Cell Volume (MCV) - Continuation Phase	Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Monocytes - Continuation Phase	Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Total Protein - Continuation Phase	Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Alanine Aminotransferase (ALT) - Maintenance Phase	Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Calcium - Maintenance Phase	Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase)
Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Glucose - Maintenance Phase	Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase)
Treatment-Emergent Adverse Events Occurring in at Least 5 Percent of Participants -- Open-Label Acute Therapy Phase	Every Visit from Week 0 up to Week 10 (Acute)
Treatment-Emergent Adverse Events Occurring in at Least 5 Percent of the Participants -- Open-Label Continuation Phase	Every Visit from Week 10 up to Week 34 (Continuation)

Trial Locations

Locations (1): For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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Sundsvall, Sweden