Trial Outcomes & Findings for Milnacipran for Treatment of Pain in Older Adults With Rheumatoid Arthritis (NCT NCT01225991)
NCT ID: NCT01225991
Last Updated: 2018-03-29
Results Overview
The Pain Rating Index ranked values associated with adjectives depicting the severity of pain from the McGill Pain Questionnaire (MPQ). The assessment is comprised of 15 adjectives, each of which is scored on a scale ranging from 0 (none) to 3 (severe) and summed to arrive at a score ranging from 0 (no pain) to 45 (worst possible pain), to measure the extent of pain/tenderness and swelling. The Pain Rating Index final scores were averaged to indicate an overall report of joint pain and stiffness.
COMPLETED
PHASE4
18 participants
Change score at baseline and 12 weeks
2018-03-29
Participant Flow
Participant milestones
| Measure |
Milnacipran, Active Drug, Open-label
All subjects will be free of antidepressant medications or opiates, or any other medications used to treat pain for at least 2 weeks prior to initiation of dose titration. Patients will be allowed to escalate up to 100 mg a day, or to their maximum tolerated dose in the course of the first week. The stable-dose phase will be a 10-week period during which patients will take medications at the final dose achieved (either 100 mg per day in divided doses, or the maximum tolerated dose of less than 100 mg per day). Final efficacy assessments will be made at the termination visit, and the study medication will be tapered down following 12 weeks of drug treatment.
Milnacipran: All subjects will be free of antidepressant medications or opiates, or any other medications used to treat pain for at least 2 weeks prior to initiation of dose titration. Patients will be allowed to escalate up to 100 mg a day: Day 1: 12.5 mg once a day; Days 2-3: 25 mg/day (12.5 mg twice daily); Days 4-7: 50 mg/day
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|---|---|
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Overall Study
STARTED
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18
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Overall Study
COMPLETED
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12
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Overall Study
NOT COMPLETED
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6
|
Reasons for withdrawal
| Measure |
Milnacipran, Active Drug, Open-label
All subjects will be free of antidepressant medications or opiates, or any other medications used to treat pain for at least 2 weeks prior to initiation of dose titration. Patients will be allowed to escalate up to 100 mg a day, or to their maximum tolerated dose in the course of the first week. The stable-dose phase will be a 10-week period during which patients will take medications at the final dose achieved (either 100 mg per day in divided doses, or the maximum tolerated dose of less than 100 mg per day). Final efficacy assessments will be made at the termination visit, and the study medication will be tapered down following 12 weeks of drug treatment.
Milnacipran: All subjects will be free of antidepressant medications or opiates, or any other medications used to treat pain for at least 2 weeks prior to initiation of dose titration. Patients will be allowed to escalate up to 100 mg a day: Day 1: 12.5 mg once a day; Days 2-3: 25 mg/day (12.5 mg twice daily); Days 4-7: 50 mg/day
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|---|---|
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Overall Study
Withdrawal by Subject
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6
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Baseline Characteristics
Milnacipran for Treatment of Pain in Older Adults With Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
Milnacipran, Active Drug, Open-label
n=12 Participants
All subjects will be free of antidepressant medications or opiates, or any other medications used to treat pain for at least 2 weeks prior to initiation of dose titration. Subjects will be allowed to escalate up to 100 mg a day or to their maximum tolerated dose in the course of the first week: Day 1: 12.5 mg once a day; Days 2-3: 25 mg/day (12.5 mg twice daily); Days 4-7: 50 mg/day (25 mg twice daily); After Day 7: 100 mg/day (50 mg twice daily). The stable-dose phase will be a 10-week period during which patients will take medications at the final dose achieved (either 100 mg per day in divided doses, or the maximum tolerated dose of less than 100 mg per day). Final efficacy assessments will be made at the termination visit, and the study medication will be tapered down following 12 weeks of drug treatment.
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|---|---|
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Age, Continuous
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67.5 years
n=5 Participants
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
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Age, Categorical
Between 18 and 65 years
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6 Participants
n=5 Participants
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Age, Categorical
>=65 years
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6 Participants
n=5 Participants
|
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Sex: Female, Male
Female
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9 Participants
n=5 Participants
|
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Sex: Female, Male
Male
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3 Participants
n=5 Participants
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Region of Enrollment
United States
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12 participants
n=5 Participants
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PRIMARY outcome
Timeframe: Change score at baseline and 12 weeksThe Pain Rating Index ranked values associated with adjectives depicting the severity of pain from the McGill Pain Questionnaire (MPQ). The assessment is comprised of 15 adjectives, each of which is scored on a scale ranging from 0 (none) to 3 (severe) and summed to arrive at a score ranging from 0 (no pain) to 45 (worst possible pain), to measure the extent of pain/tenderness and swelling. The Pain Rating Index final scores were averaged to indicate an overall report of joint pain and stiffness.
Outcome measures
| Measure |
Milnacipran, Active Drug, Open-label
n=12 Participants
All subjects will be free of antidepressant medications or opiates, or any other medications used to treat pain for at least 2 weeks prior to initiation of dose titration. Subjects will be allowed to escalate up to 100 mg a day or to their maximum tolerated dose in the course of the first week: Day 1: 12.5 mg once a day; Days 2-3: 25 mg/day (12.5 mg twice daily); Days 4-7: 50 mg/day (25 mg twice daily); After Day 7: 100 mg/day (50 mg twice daily). The stable-dose phase will be a 10-week period during which patients will take medications at the final dose achieved (either 100 mg per day in divided doses, or the maximum tolerated dose of less than 100 mg per day). Final efficacy assessments will be made at the termination visit, and the study medication will be tapered down following 12 weeks of drug treatment.
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|---|---|
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Pain Rating Index
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-3.7 units on a scale
Standard Deviation 6.6
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SECONDARY outcome
Timeframe: Change scores from Week 1 to Week 12 of energy and fatigueThe Visual Analogue Scale to Evaluate Fatigue (VAS-F) is an assessment of fatigue severity. The Visual Analogue Scale (VAS) measures a characteristic or attitude that ranges across a continuum of values from none (0) to an extreme amount of fatigue and energy (10). Scores fall between 0 and 10 anchored by word descriptors at each end and the patient marks on the line the point that they feel represents their perception of their current state. The scale consists of 18 items relating to the subjective experience of fatigue. Two subscales are summed separately and reported as follows: Items 1-5 and 11-18 represent fatigue from none (0) to extreme fatigue (10) and items 6-10 represent energy from none (0) to extreme energy (10). The outcome measures the change scores of energy and fatigue from Week 1 to Week 12. The VAS subscales for Fatigue Scale range: 0-130 and Energy Scale range: 0-50 with higher scores indicating greater energy and fatigue.
Outcome measures
| Measure |
Milnacipran, Active Drug, Open-label
n=12 Participants
All subjects will be free of antidepressant medications or opiates, or any other medications used to treat pain for at least 2 weeks prior to initiation of dose titration. Subjects will be allowed to escalate up to 100 mg a day or to their maximum tolerated dose in the course of the first week: Day 1: 12.5 mg once a day; Days 2-3: 25 mg/day (12.5 mg twice daily); Days 4-7: 50 mg/day (25 mg twice daily); After Day 7: 100 mg/day (50 mg twice daily). The stable-dose phase will be a 10-week period during which patients will take medications at the final dose achieved (either 100 mg per day in divided doses, or the maximum tolerated dose of less than 100 mg per day). Final efficacy assessments will be made at the termination visit, and the study medication will be tapered down following 12 weeks of drug treatment.
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|---|---|
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Visual Analogue Scale to Evaluate Fatigue (VAS-F)
Fatigue Subscale
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15.2 units on a scale
Standard Deviation 18.9
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Visual Analogue Scale to Evaluate Fatigue (VAS-F)
Energy Subscale
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3.7 units on a scale
Standard Deviation 16.4
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SECONDARY outcome
Timeframe: Weeks 1-4, 6, 8, 10, 12The UKU assessment will rate the number of participants with emerging adverse events.
Outcome measures
| Measure |
Milnacipran, Active Drug, Open-label
n=12 Participants
All subjects will be free of antidepressant medications or opiates, or any other medications used to treat pain for at least 2 weeks prior to initiation of dose titration. Subjects will be allowed to escalate up to 100 mg a day or to their maximum tolerated dose in the course of the first week: Day 1: 12.5 mg once a day; Days 2-3: 25 mg/day (12.5 mg twice daily); Days 4-7: 50 mg/day (25 mg twice daily); After Day 7: 100 mg/day (50 mg twice daily). The stable-dose phase will be a 10-week period during which patients will take medications at the final dose achieved (either 100 mg per day in divided doses, or the maximum tolerated dose of less than 100 mg per day). Final efficacy assessments will be made at the termination visit, and the study medication will be tapered down following 12 weeks of drug treatment.
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|---|---|
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(UKU) Side Effects Rating Scale Profile
Micturition Disturbances
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2 Participants
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(UKU) Side Effects Rating Scale Profile
Increased Tendency to Sweating
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3 Participants
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(UKU) Side Effects Rating Scale Profile
Ejaculatory Dysfunction
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1 Participants
|
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(UKU) Side Effects Rating Scale Profile
Tension Headache
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2 Participants
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(UKU) Side Effects Rating Scale Profile
Concentration difficulties
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1 Participants
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(UKU) Side Effects Rating Scale Profile
Asthenia / Lassitude / Increased Fatiguability
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6 Participants
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(UKU) Side Effects Rating Scale Profile
Sleepiness / Sedation
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2 Participants
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(UKU) Side Effects Rating Scale Profile
Failing Memory
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1 Participants
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(UKU) Side Effects Rating Scale Profile
Depression
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2 Participants
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(UKU) Side Effects Rating Scale Profile
Reduced Duration of Sleep
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1 Participants
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(UKU) Side Effects Rating Scale Profile
Nausea / Vomiting
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3 Participants
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SECONDARY outcome
Timeframe: Week 1 and 12Depressive symptoms: Repeated assessment of depressive symptoms severity will be made using the Profile of Mood States (POMS). The scale consisted of 65 adjectives rated on 5-point scale 0= not at all; 1=a little; 2=moderately; 3=quite a bit; 4=extremely. Five subscales were included in analysis: tension-anxiety (9 items, score range: 0-36), depression (15 items, range 0-60), friendliness (12 items, range 0-48), vigor-activity (8 items, range 0-32), and fatigue (7 items, range 0-28). Higher vigor-activity and friendliness scores reflect a good mood or emotion (high scores indicating better outcomes), and low scores in the other subscales (tension, depression, and fatigue) reflect a good mood or emotion (low scores indicating better outcomes).
Outcome measures
| Measure |
Milnacipran, Active Drug, Open-label
n=12 Participants
All subjects will be free of antidepressant medications or opiates, or any other medications used to treat pain for at least 2 weeks prior to initiation of dose titration. Subjects will be allowed to escalate up to 100 mg a day or to their maximum tolerated dose in the course of the first week: Day 1: 12.5 mg once a day; Days 2-3: 25 mg/day (12.5 mg twice daily); Days 4-7: 50 mg/day (25 mg twice daily); After Day 7: 100 mg/day (50 mg twice daily). The stable-dose phase will be a 10-week period during which patients will take medications at the final dose achieved (either 100 mg per day in divided doses, or the maximum tolerated dose of less than 100 mg per day). Final efficacy assessments will be made at the termination visit, and the study medication will be tapered down following 12 weeks of drug treatment.
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|---|---|
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Profile of Mood States (POMS)
POMS Anxiety Week 1
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5.75 units on a scale
Standard Deviation 5.12
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Profile of Mood States (POMS)
POMS Depression Week 1
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4.08 units on a scale
Standard Deviation 3.60
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Profile of Mood States (POMS)
POMS Vigor Week 1
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13.00 units on a scale
Standard Deviation 6.03
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Profile of Mood States (POMS)
POMS Fatigue Week 1
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6.67 units on a scale
Standard Deviation 6.27
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Profile of Mood States (POMS)
POMS Friendliness Week 1
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6.42 units on a scale
Standard Deviation 3.82
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Profile of Mood States (POMS)
POMS Anxiety Week 12
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5.50 units on a scale
Standard Deviation 4.56
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Profile of Mood States (POMS)
POMS Depression Week 12
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3.92 units on a scale
Standard Deviation 6.64
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Profile of Mood States (POMS)
POMS Vigor Week 12
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16.83 units on a scale
Standard Deviation 5.92
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Profile of Mood States (POMS)
POMS Fatigue Week 12
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6.00 units on a scale
Standard Deviation 4.86
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Profile of Mood States (POMS)
POMS Friendliness Week 12
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9.42 units on a scale
Standard Deviation 5.99
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SECONDARY outcome
Timeframe: Change Scores from Week 1 to Week 12Resilience: the Connor-Davidson Resilience scale (CD-RISC) quantifies stress coping ability. The CD-RISC is a 25-item self-administered scale, although where necessary, a staff professional could read out each question to the subject and record the answer. The subject is directed to respond to each question with reference to the previous month, understanding that if a particular situation has not arisen in this time, then the response should be determined by how the person thinks they would have reacted. Scoring of the full 25 item scale is based on summing the total of each item, which is scored from 0-4. The full range is therefore from 0 to 100, with higher scores reflecting greater resilience. The outcome measure is a change score from Week 1 to Week 12.
Outcome measures
| Measure |
Milnacipran, Active Drug, Open-label
n=12 Participants
All subjects will be free of antidepressant medications or opiates, or any other medications used to treat pain for at least 2 weeks prior to initiation of dose titration. Subjects will be allowed to escalate up to 100 mg a day or to their maximum tolerated dose in the course of the first week: Day 1: 12.5 mg once a day; Days 2-3: 25 mg/day (12.5 mg twice daily); Days 4-7: 50 mg/day (25 mg twice daily); After Day 7: 100 mg/day (50 mg twice daily). The stable-dose phase will be a 10-week period during which patients will take medications at the final dose achieved (either 100 mg per day in divided doses, or the maximum tolerated dose of less than 100 mg per day). Final efficacy assessments will be made at the termination visit, and the study medication will be tapered down following 12 weeks of drug treatment.
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|---|---|
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Connor-Davidson Resilience Scale (CD-RISC)
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-2.2 units on a scale
Standard Deviation 8.0
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Adverse Events
Milnacipran, Active Drug, Open-label
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Milnacipran, Active Drug, Open-label
n=18 participants at risk
All subjects will be free of antidepressant medications or opiates, or any other medications used to treat pain for at least 2 weeks prior to initiation of dose titration. Subjects will be allowed to escalate up to 100 mg a day or to their maximum tolerated dose in the course of the first week: Day 1: 12.5 mg once a day; Days 2-3: 25 mg/day (12.5 mg twice daily); Days 4-7: 50 mg/day (25 mg twice daily); After Day 7: 100 mg/day (50 mg twice daily). The stable-dose phase will be a 10-week period during which patients will take medications at the final dose achieved (either 100 mg per day in divided doses, or the maximum tolerated dose of less than 100 mg per day). Final efficacy assessments will be made at the termination visit, and the study medication will be tapered down following 12 weeks of drug treatment.
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|---|---|
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Gastrointestinal disorders
Nausea
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16.7%
3/18
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Psychiatric disorders
Concentration Difficulties
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5.6%
1/18
|
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Psychiatric disorders
Asthenia
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33.3%
6/18
|
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Psychiatric disorders
Sleepiness / Sedation
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11.1%
2/18
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Psychiatric disorders
Failing Memory
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5.6%
1/18
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Psychiatric disorders
Depression
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11.1%
2/18
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Psychiatric disorders
Reduced Duration of Sleep
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5.6%
1/18
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Renal and urinary disorders
Micturition Disturbances
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11.1%
2/18
|
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Nervous system disorders
Increased Tendency to Sweat
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16.7%
3/18
|
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Reproductive system and breast disorders
Ejaculatory Dysfunction
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5.6%
1/18
|
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General disorders
Tension Headache
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11.1%
2/18
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Additional Information
Dr. Helen Lavretsky,
University of California, Los Angeles
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place