A Study Comparing Duloxetine and Placebo in Assessing Energy and Vitality in Major Depressive Disorder (MDD) Patients

Change From Baseline to 12 Week and 9 Month Endpoints in the 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score and HAMD-24 Subscales (8 Week Endpoint for Maier Subscale)

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). Please see baseline demographics for subscale total scores.

Time frame: Baseline, 8 weeks, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in the HAMD-24 Total Score

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in the HAMD-24 Item 1:Depressed Mood

Measures depressed mood on a scale of 0 (absent) to 4 (very depressed).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 2:Feelings of Guilt

Measures feelings of guilt on a scale of 0 (absent) to 4 (very guilty).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 3:Suicide

Measures thoughts of suicide on a scale of 0 (absent) to 4 (attempts suicide).

Time frame: Baseline, 12 weeks, 9 Months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 4:Insomnia Early

Measures early insomnia on a scale of 0 (no difficulty falling asleep) to 2 (complains of nightly difficulty falling asleep).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 5:Insomnia Middle

Measures middle insomnia on a scale of 0 (no difficulty) to 2 (waking during the night).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 6:Insomnia Late

Measures late insomnia on a scale of 0 (no difficulty) to 2 (unable to fall asleep again if gets out of bed).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 9 Month Endpoint in HAMD-24 - Item 7:Work and Activities

Item 7 of the HAMD-24 assesses loss of interest or pleasure in work and activities and is an essential symptom in MDD. Scores range from 0 (no difficulty/no loss) to 4 (difficulty/loss).

Time frame: Baseline, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 8:Retardation

Measures slowness of thought and speech; impaired ability to concentrate; decreased motor activity on a scale of 0 (normal speech and thought) to 4 (complete stupor).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 9:Agitation

Measures agitation on a scale of 0 (none) to 4 (hand-wringing, nail-biting)

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 10:Anxiety (Psychic)

Measures anxiety on a scale of 0 (no difficulty) to 4 (fears expressed)

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 11:Anxiety (Somatic)

Measures physiological concomitants of anxiety on a scale of 0 (absent) to 4 (incapacitating).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 12:Somatic Symptoms/Gastrointestinal

Measures gastrointestical somatic symptoms on a scale of 0 (none) to 2 (difficulty eating, requires medication for symptoms).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 13:Somatic Symptoms/General

Measures general somatic symptoms on a scale of 0 (none) to 2 (any clear-cut symptoms).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 14:Genital Symptoms

Measures genital symptoms (loss of libido, menstrual disturbances) on a scale of 0 (absent) to 2 (severe).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 15:Hypochondriasis

Measures hypochondriasis on a scale of 0 (not present) to 4 (hypochondriacal delusions).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 16:Loss of Weight

Measures weight loss since last visit on a scale of 0 (no weight loss) to 2 (definite weight loss caused by present illness).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 17:Insight

Measures insight on a scale of 0 (acknowledges being depressed and ill) to 2 (denies being ill at all).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 18A:Diurnal Variation

Measures whether symptoms are worse in morning or evening on a scale of 0 (no variation), 1 (worse in morning), or 2 (worse in evening).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 18B:Diurnal Variation-Severity

Measures the severity of the diurnal variation on a scale of 0 (none) to 2 (severe).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 19: Depersonalization and Derealization

Measures feelings of unreality on a scale of 0 (absent) to 4 (incapacitating).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 20:Paranoid Symptoms

Measures paranoid symptoms on a scale of 0 (none) to 2 (severe).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 21:Obsessional and Compulsive Symptoms

Measures obsessional and compulsive symptoms on a scale of 0 (absent) to 2 (severe).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 22B:Helplessness

Measures feelings of helplessness on a scale of 0 (absent) to 4 (severe).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 23B:Hopelessness

Measures feelings of hopelessness on a scale of 0 (absent) to 4 (expresses feelings of discouragement, despair, and/or pessimism about the future which cannot be dispelled).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 24B:Worthlessness

Measures feelings of worthlessness on a scale of 0 (absent) to 4 (severe).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week Endpoint in 30-Item Brief Profile of Mood States (BPOMS) Scale and Subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment).

The 30-item BPOMS measures mood states and has 6 factors: tension-anxiety, depression-dejection, anxiety-hostility, fatigue, confusion, and vigor. Item scores: 0 (not at all) to 4 (extremely). Each factor scores range from 0 to 20. The Total score is sum of all factor scores minus the factor score for vigor (Total=Ten+Dep+Ang+Fat+Con-Vig).

Time frame: Baseline, 12 weeks

Change From Baseline to 9 Month Endpoint in 30-Item Brief Profile of Mood States (BPOMS) Scale and Subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment)

The 30-item BPOMS measures mood states and has 6 factors: tension-anxiety, depression-dejection, anxiety-hostility, fatigue, confusion, and vigor. Item scores: 0 (not at all) to 4 (extremely). Each factor scores range from 0 to 20. The Total score is sum of all factor scores minus the factor score for vigor (Total=Ten+Dep+Ang+Fat+Con-Vig).

Time frame: Baseline, 9 months

Change From Baseline to 12 Week Endpoint in Sheehan Disability Scale (SDS) Total Score and Subscores

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. Individual item scores range from 0 to 10. Total scores range from 0 to 30 with higher values indicating greater disruption in the patient's work/social/family life.

Time frame: Baseline, 12 weeks

Change From Baseline to 9 Month Endpoint in Sheehan Disability Scale (SDS) Total Score and Subscores

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. Individual item scores range from 0 to 10. Total scores range from 0 to 30 with higher values indicating greater disruption in the patient's work/social/family life.

Time frame: Baseline, 9 months

Path Analysis of BPOMS Total Score to Overall Improvement in HAMD-24 Item 7

Relative contribution of improvement on the mood states, defined by BPOMS total score (calculated from subscales) to overall improvement in work and activities, HAMD-24 item 7 using path analysis.

Time frame: Over 12 weeks

Path Analysis of BPOMS Total Score to Overall Improvement in HAMD-24 Item 7 - Percent of Total Effect

For Group A, at least one effect was in the opposite direction, percent of total effect was not calculated.

Time frame: over 12 weeks

Path Analysis of BPOMS Total Score to Overall Improvement in Sheehan Disability Scale (SDS) Total Score

Relative contribution of improvement on the mood states, defined by BPOMS total score (determined from subscales) to overall improvement in SDS total score using path analysis.

Time frame: over 12 weeks

Path Analysis of BPOMS Total Score to Overall Improvement in SDS Total Score - Percent of Total Effect

For Group A, at least one effect was in the opposite direction, percent of total effect was not calculated.

Time frame: Over 12 weeks

Change From Baseline to 12 Week and 9 Month Endpoints in 16-Item Quick Inventory of Depressive Symptomatology Self Report (QIDS16SR) Total Score

A 16-item patient-rated measure of depressive symptomatology. The total score ranges from 0 to 27 with higher scores indicative of greater severity.

Time frame: Baseline, 12 weeks, 9 months

Probability of Remission at 12 Week Endpoint and Sustained Remission at 9 Month Endpoint

Probability of remission as measured by the HAMD17 Total Score ≤ 7 and by the QIDS16SR Total Score ≤ 5. The visitwise percentages of patients meeting criteria in the Acute Therapy Phase for remission (visitwise binary outcome, yes/no) will be analyzed using a categorical, pseudo-likelihood-based repeated measures approach. This analysis will include the fixed, categorical effects of treatment, investigator, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline score.

Time frame: 12 weeks, 9 months

Probability of Response at 12 Week Endpoint

Probability of response as measured by ≥ 50% Improvement in the HAMD17 Total Score and ≥ 50% Improvement in the QIDS16SR Total Score. The visitwise percentages of patients meeting criteria in the Acute Therapy Phase for response (visitwise binary outcome, yes/no) will be analyzed using a categorical, pseudo-likelihood-based repeated measures approach. This analysis will include the fixed, categorical effects of treatment, investigator, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline score.

Time frame: 12 weeks

Change From Baseline to 12 Week and 9 Month Endpoints in Pain Numerical Rating Scale (NRS)

Item 1=Average musculoskeletal pain severity over the last week as measured by an 11-point Likert scale. Scores range from 0 (no pain) to 10 (worst possible pain). Item 7=How much they have been bothered by pain over the last week. Scores range from 0 (not bothered at all)to 10 (extremely bothered).

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoint in the Clinical Global Impression-Severity Scale (CGI-S)

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.

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ)

A 7-item patitent-rated questionnaire pertaining to a patient's cognitive and physical well-being. It assesses motivation, wakefulness, energy, focus, recall, word-finding difficulty, and mental acuity. Each of the 7 questions is scored on a 6-point scale ranging fom 1 (greater than normal) to 6 (totally absent). Total score ranges from 7 to 42.

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in the Social Adaptation Self-evaluation Scale (SASS) Total Score

A 21-item self-rated scale that evaluates patient social motivation and behavior in depression. Each of the 21 items is scored from 0 (minimal social adjustment) to 3 (maximal social adjustment). Total score ranges from 0 to 60.

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in Blood Pressure

Sitting systolic and diastolic blood pressure.

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in Pulse Rate

Time frame: Baseline, 12 weeks, 9 months

Change From Baseline to 12 Week and 9 Month Endpoints in Weight

Time frame: Baseline, 12 weeks, 9 months

Abnormal Vital Signs at Anytime Over 12 Weeks

Time frame: over 12 weeks

Abnormal Vital Signs at Anytime Over 9 Months

Time frame: over 9 months

Abnormal Vital Signs at 12 Week Endpoint

Time frame: 12 weeks

Abnormal Vital Signs at 9 Month Endpoint

Time frame: 9 months

Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Bilirubin, Creatinine, Uric Acid

Time frame: Baseline, 12 weeks, 9 months

Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Hematocrit

Time frame: Baseline, 12 weeks, 9 months

Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Mean Cell Volume (MCV)

Time frame: Baseline, 12 weeks, 9 months

Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Chloride, Urea Nitrogen, Cholesterol, Sodium

Time frame: Baseline, 12 weeks, 9 months

Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Platelet Count

Time frame: Baseline, 12 weeks, 9 months

Statistically Significant Changes in Baseline to 9 Month Endpoint Laboratory Values - Alkaline Phosphatase

Time frame: baseline, 9 months

Statistically Significant Changes in Baseline to 9 Month Endpoint Laboratory Values - Hemoglobin

Time frame: Baseline, 9 months

Statistically Significant Abnormal Laboratory Values at Anytime/12 Week Endpoint

The number of participants with statistically significant abnormal lab values at anytime and at 12 week endpoint were the same.

Time frame: over 3 months

Statistically Significant Abnormal Laboratory Values at Anytime During 9 Months

Time frame: over 9 months

Statistically Significant Abnormal Laboratory Values at 9 Month Endpoint

Time frame: 9 months

Summary of Adverse Events Leading to Discontinuation

Time frame: over 9 months