| Trial | Phase | Enrollment | Study Type | Start Date | Status |
|---|
| Pain Assessment and Quality of Life in Back Pain Patients: Role of Milnacipran [NCT01221740] | Phase 3 | 0 participants (Actual) | Interventional | 2010-08-31 | Withdrawn(stopped due to Company decided to discontinue) |
| A Phase III Pivotal, Multicenter, Double-blind, Randomized, Placebo-Controlled Monotherapy Study of Milnacipran for the Treatment of Fibromyalgia. [NCT00314249] | Phase 3 | 1,025 participants (Actual) | Interventional | 2006-04-30 | Completed |
| Effects of Antidepressant on Postsynaptic Signal Transduction in Serotonergic System of Depressed Patients [NCT01352572] | | 300 participants (Anticipated) | Interventional | 2002-01-31 | Active, not recruiting |
| The Effect of Milnacipran on Fatigue and Quality of Life in a Lupus Cohort [NCT01359826] | Phase 4 | 0 participants (Actual) | Interventional | 2011-10-31 | Withdrawn(stopped due to PI has let the institution. We are unable to locate any study documents that would indicate study enrollment) |
| An Open-Label Pilot Study to Assess Potential Mechanisms for Fibromyalgia in Peripheral Tissue Innervation That Could Predict Therapeutic Responsiveness to Milnacipran [NCT01125423] | Phase 4 | 27 participants (Actual) | Interventional | 2010-05-31 | Completed |
| Effects of Milnacipran on Widespread Mechanical and Thermal Hyperalgesia of Fibromyalgia Patients [NCT01294059] | Phase 1 | 51 participants (Actual) | Interventional | 2009-11-30 | Completed |
| Effect of Milnacipran Versus Gabapentin or Combination of Both in Fibromyalgia Syndrome [NCT05384210] | | 75 participants (Anticipated) | Interventional | 2022-06-30 | Enrolling by invitation |
| Open Label Study of Milnacipran in the Preventive Treatment of Episodic Migraine With and Without Aura and Chronic Migraine. [NCT01319825] | Phase 4 | 45 participants (Anticipated) | Interventional | 2011-04-30 | Not yet recruiting |
| "An Exploratory, Randomized, Single Blinded, Placebo-Controlled, Dose-Ranging Study of the Safety and Efficacy of MILNACIPRAN in Subjects With Chronic Shoulder Pain" [NCT01289236] | Phase 4 | 40 participants (Actual) | Interventional | 2009-10-31 | Completed |
| A Randomized Trial Comparing Efficacy and Tolerability of Levomilnacipran Switch Versus Adjunctive Quetiapine in Major Depressive Disorder (MDD) With Inadequate Response to SSRIs [NCT02720198] | Phase 3 | 60 participants (Actual) | Interventional | 2017-01-23 | Completed |
| A Double-blind, Placebo-Controlled, Fixed-Dose Study of Levomilnacipran SR in Patients With Major Depressive Disorder [NCT01377194] | Phase 3 | 568 participants (Actual) | Interventional | 2011-06-30 | Completed |
| A Double-Blind, Placebo-Controlled, Enriched Enrollment Randomized Withdrawal Study to Evaluate the Efficacy of Milnacipran in the Treatment of Pain Due to Osteoarthritis [NCT01329406] | Phase 4 | 50 participants (Anticipated) | Interventional | 2011-07-31 | Recruiting |
| A Multicenter, Randomized, Double-blind, Placebo-Controlled Withdrawal Study to Evaluate the Safety, Tolerability, and Efficacy of Milnacipran in Pediatric Patients With Primary Fibromyalgia [NCT01328002] | Phase 2 | 116 participants (Actual) | Interventional | 2011-04-30 | Terminated |
| A Double-blind, Placebo-Controlled, Fixed-Dose Study of F2695 SR in Patients With Major Depressive Disorder [NCT00969709] | Phase 3 | 724 participants (Actual) | Interventional | 2009-09-30 | Completed |
| A Pilot Study on the Combined Use of Cognitive Behavioral Therapy (CBT) and Milnacipran [NCT01038323] | Phase 4 | 58 participants (Actual) | Interventional | 2009-12-31 | Completed |
| Evaluation of the Antinociceptive and Analgesic Effects of Milnacipran. An Exploratory Placebo-controlled Clinical Trial in Fibromyalgia Out-patients [NCT00757679] | Phase 2 | 153 participants (Actual) | Interventional | 2006-09-30 | Completed |
| [NCT00606203] | | 120 participants (Anticipated) | Interventional | 2007-09-30 | Recruiting |
| A European Phase III, Multicentre, Double-blind, Randomised, Monotherapy, 12-month Study of Milnacipran for the Treatment of the Fibromyalgia Syndrome [NCT00757731] | Phase 3 | 490 participants (Actual) | Interventional | 2006-09-30 | Completed |
| A Double-blind, Placebo-Controlled, Flexible-Dose Study of F2695 SR in Patients With Major Depressive Disorder [NCT01034462] | Phase 3 | 442 participants (Actual) | Interventional | 2009-12-31 | Completed |
| Prediction of Inter-individual Differences in the Response to Morphine by Psychophysical Assessment of Pain Enhancing and Inhibiting Mechanisms in Patients With Chronic Neuropathic Pain [NCT01914042] | Phase 2 | 150 participants (Anticipated) | Interventional | 2013-07-31 | Recruiting |
| A Multicenter, Randomized, Double-blind, Placebo-Controlled, Relapse-Prevention Study With F2695 SR in Patients With Major Depressive Disorder [NCT01085812] | Phase 3 | 734 participants (Actual) | Interventional | 2010-03-31 | Completed |
| A Placebo Controlled, Randomized, Double Blind Trial of Milnacipran for the Treatment of Idiopathic Neuropathy Pain [NCT01288937] | Phase 3 | 6 participants (Actual) | Interventional | 2011-04-05 | Terminated(stopped due to Poor recruitment) |
| A Multicenter, Open-label, 52-Week Extension Study to Evaluate the Safety and Efficacy of Milnacipran in Pediatric Patients With Primary Fibromyalgia [NCT01331109] | Phase 2 | 57 participants (Actual) | Interventional | 2011-04-30 | Terminated |
| A Randomized, Double-blind,Placebo-controlled, Two-way Crossover Study to Evaluate the Effect of Milnacipran on Pain Processing and Functional Magnetic Resonance Imaging Activation Patterns in Patients With Fibromyalgia [NCT01173055] | Phase 4 | 22 participants (Actual) | Interventional | 2010-06-30 | Completed |
| Novel Medication as a Potential Smoking Cessation Aid [NCT02265367] | | 56 participants (Actual) | Interventional | 2015-01-31 | Completed |
| A Multicenter, Randomized, Double-blind, Placebo-Controlled Discontinuation Study of the Durability of Effect of Milnacipran for the Treatment of Fibromyalgia in Patients Receiving Long-term Milnacipran Treatment [NCT01014585] | Phase 4 | 340 participants (Actual) | Interventional | 2009-11-30 | Completed |
| "The Effect of Milnacipran or Placebo on Ventricular Lactate Levels and Fibromyalgia Induced Brain Fog." [NCT01108731] | Phase 2/Phase 3 | 37 participants (Actual) | Interventional | 2010-03-31 | Completed |
| A Multicenter, Randomized, Double-Blind, Placebo-Controlled Switch Study to Evaluate the Safety, Tolerability and Efficacy of Milnacipran in Patients With an Inadequate Response to Duloxetine for the Treatment of Fibromyalgia [NCT01077375] | Phase 4 | 107 participants (Actual) | Interventional | 2010-02-28 | Completed |
| A Double-blind, Placebo-Controlled, Flexible-Dose Study of F2695 SR in Patients With Major Depressive Disorder [NCT00969150] | Phase 3 | 362 participants (Actual) | Interventional | 2009-09-30 | Completed |
| An Open-label Trial of Milnacipran for the Treatment of Pain in Rheumatoid Arthritis (RA) in Older Adults [NCT01225991] | Phase 4 | 18 participants (Actual) | Interventional | 2010-11-30 | Completed |
| A Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study of Milnacipran 100 And 200 MG Daily in Patients With Fibromyalgia: Effects On 24 Hour Ambulatory Blood Pressure [NCT00618956] | Phase 3 | 321 participants (Actual) | Interventional | 2007-10-31 | Completed |
| Milnacipran in the Treatment of Widespread, Non-Joint Pain in Rheumatoid Arthritis [NCT01207453] | Phase 4 | 49 participants (Actual) | Interventional | 2011-01-31 | Completed |
| The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia [NCT01234675] | Phase 4 | 19 participants (Actual) | Interventional | 2010-11-30 | Completed |
| [NCT00793520] | Phase 3 | 2 participants (Actual) | Interventional | 2008-11-30 | Terminated |
| A Phase III Pivotal, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of Milnacipran for the Treatment of Fibromyalgia [NCT00098124] | Phase 3 | 1,200 participants | Interventional | 2004-11-30 | Completed |
| A European Phase III, Multicentre, Double-blind, Randomised, Placebo-controlled Monotherapy Study of Milnacipran for the Treatment of Fibromyalgia Syndrome [NCT00436033] | Phase 3 | 1,429 participants (Actual) | Interventional | 2006-02-28 | Completed |
| Evaluation of the Initial Prescription of Ketamine and Milnacipran Forin Depression in Patients With a Progressive Disease [NCT02783430] | Phase 2/Phase 3 | 80 participants (Anticipated) | Interventional | 2016-09-08 | Recruiting |
| An Exploratory Randomized Placebo Controlled Trial of Milnacipran in Patients With Chronic Neuropathic Low Back Pain [NCT01225068] | Phase 2 | 40 participants (Actual) | Interventional | 2010-10-31 | Completed |
| Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism [NCT01337700] | Phase 4 | 10 participants (Actual) | Interventional | 2011-02-28 | Completed |
| A Double-blind, Randomized, Placebo- and Active-Controlled Study of F2695 SR in Adult Patients With Fatigue Associated With Major Depressive Disorder [NCT01254305] | Phase 2 | 262 participants (Actual) | Interventional | 2011-04-30 | Completed |
| Milnacipran and Neurocognition, Pain and Fatigue in Fibromyalgia: A 13-week Randomized, Placebo Controlled Cross Over Trial [NCT01829243] | Phase 3 | 26 participants (Actual) | Interventional | 2011-07-31 | Completed |
| Neural Mechanisms of Monoaminergic Engagement in Late-life Depression Treatment Response (NEMO) [NCT03128021] | Phase 4 | 80 participants (Anticipated) | Interventional | 2017-05-24 | Recruiting |
| Phase III Multi-Center, Double-Blind, Comparative Study of Effexor XR for the Treatment of Depression [NCT00225511] | Phase 3 | 590 participants (Anticipated) | Interventional | 2004-06-30 | Completed |
| A Multicenter, Randomized, Open-Label, Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Milnacipran When Added to Pregabalin in the Treatment of Fibromyalgia [NCT00797797] | Phase 3 | 364 participants (Actual) | Interventional | 2008-11-30 | Completed |
| A Double-blind, Placebo- and Active-controlled Evaluation of the Safety and Efficacy of Levomilnacipran ER in Pediatric Patients 7-17 Years With Major Depressive Disorder [NCT03569475] | Phase 3 | 501 participants (Actual) | Interventional | 2018-07-06 | Completed |
| [NCT01747044] | Phase 2 | 48 participants (Anticipated) | Interventional | 2013-04-30 | Recruiting |
| A Double-blind, Placebo- and Active-Controlled Evaluation of the Safety and Efficacy of Levomilnacipran ER in Adolescent Patients With Major Depressive Disorder [NCT02431806] | Phase 3 | 552 participants (Actual) | Interventional | 2015-06-23 | Completed |
| An Open Label Trial of Milnacipran in the Treatment of Women With Provoked Vestibulodynia [NCT01304589] | Phase 3 | 31 participants (Actual) | Interventional | 2010-10-31 | Completed |
| Double-blind Placebo-controlled Trial of Levomilnacipran in Geriatric Depression [NCT02466958] | Phase 4 | 29 participants (Actual) | Interventional | 2016-06-30 | Completed |
| A Multicenter, Randomized, Double-blind, Placebo-Controlled, Relapse-Prevention Study With Levomilnacipran ER in Patients With Major Depressive Disorder [NCT02288325] | Phase 4 | 644 participants (Actual) | Interventional | 2014-11-18 | Completed |
| Uncovering Neural and Immune Mechanisms of Chronic Pain in Post Treatment Lyme Syndrome [NCT02687165] | | 4 participants (Actual) | Interventional | 2016-01-16 | Terminated(stopped due to Slow recruitment due to strict inclusion/exclusion criteria) |
| A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy of Milnacipran in the Treatment of Irritable Bowel Syndrome [NCT01471379] | Phase 2 | 2 participants (Actual) | Interventional | 2012-04-30 | Terminated(stopped due to Due to recruitment difficulties the study is terminated.) |
| Effectiveness of the Norepinephrine and Serotonin Reuptake Inhibitor Levomilnacipran in Healthy Males [NCT03249311] | Phase 4 | 36 participants (Actual) | Interventional | 2018-03-02 | Active, not recruiting |
| A Randomized Double Blind Placebo Control Trial of Milnacipran for Migraine Pain [NCT01393522] | | 37 participants (Actual) | Interventional | 2011-06-30 | Completed |
| Milnacipran for the Pain, Sensory Sensitization and Mood Changes in Knee Osteoarthritis [NCT01510457] | Phase 4 | 46 participants (Actual) | Interventional | 2010-11-30 | Completed |
| Open-label Milnacipran for Persistent Knee Pain One Year After Total Knee Arthroplasty (TKA) [NCT01780389] | Phase 4 | 5 participants (Actual) | Interventional | 2010-10-31 | Completed |
| A Ten-Week, Randomized, Double-Blind, Placebo-Controlled Parallel-Group Study of Milnacipran for Radicular Pain Associated With Lumbosacral Disk Disease [NCT01777581] | Phase 4 | 13 participants (Actual) | Interventional | 2010-03-31 | Completed |
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] |
Change From Baseline in the Multi-Dimensional Fatigue Inventory (MFI) Total Score at Visit TX12.
"Change from Baseline in the Multi-Dimensional Fatigue Inventory (MFI) total score at TX12. Negative differences indicate decrease of fatigue.~MFI is a subjective report of fatigue symptoms consisting of 20 items that can be scored to produce 5 dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. The MFI is a 1-5 scale with 1=yes, that is true and 5=no, that is not true." (NCT00314249)
Timeframe: Baseline through end of week 12 (Visit TX12)
| Intervention | units on scale (Mean) |
|---|
| Placebo | -3.96 |
| Milnacipran | -5.50 |
Composite Pain Responder Status
"Composite Pain Responder Status is the number of responders based on two domains: (1) 30% reduction in pain (as recorded in the Patient Experience Diary [PED], electronic diary, during the morning report; 24 hour recall); and (2) Patient Global Impression of Change (PGIC) score of very much improved or much improved." (NCT00314249)
Timeframe: At the end of three-month stable dose treatment phase
| Intervention | Pain Responder Participants (Number) |
|---|
| Placebo | 90 |
| Milnacipran | 147 |
Composite Syndrome Responder Status
"Composite Syndrome Responder Status is the number of responders based on 3 domains: (1) 30% reduction in pain (as recorded in the Patient Experience Diary [PED], electronic diary, during the morning report; 24 hour recall); (2) patient global impression of change (PGIC) score of very much improved and much improved; and (3) physical function improvement of 6 or more points on Short Form-36 Physical Component Summary (SF-36 PCS)" (NCT00314249)
Timeframe: At the end of the three-month stable dose treatment phase
| Intervention | Syndrome Responder Participants (Number) |
|---|
| Placebo | 56 |
| Milnacipran | 103 |
Time-Weighted Average of Patient Experience Diary (PED) Reported Morning 24-Hour Recall Pain Scores for Weeks 1-12 of the Stable Dose Phase
"Time-weighted average (area under the curve [AUC]) of the weekly average Patient Experience Diary (PED)-reported morning recall pain scores for weeks 1 through 12 of the stable dose treatment phase is the area under the Patient Experience Diary (PED)-time curve estimated using the trapezoidal method and normalized by time.~PED is the Patient Experience Diary, an electronic diary system used for collection of patient self-reported pain data. Outcome measure is assessed using the VAS Pain Intensity Scale from 0-100 millimeters anchored at 0 mm (no pain) to 100 mm (worst possible pain)." (NCT00314249)
Timeframe: Weeks 1 through 12 of the stable dose treatment phase (Visit TX0-TX12)
| Intervention | units on scale (Mean) |
|---|
| Placebo | 48.0 |
| Milnacipran | 41.2 |
Time-Weighted Average of Patient Global Impression of Change (PGIC) From Visit TX0-TX12.
"Time-weighted average (area under the curve [AUC]) for Patient Global Impression of Change (PGIC) from Visit TX0-TX12 is the area under the PGIC-time curve estimated using the trapezoidal method and normalized by time.~PGIC is an efficacy assessment on a scale of 1-7 taken at visits TX0-TX12. The wording of the assessment is as follows: Since the start of the study, overall my fibromyalgia is: 1=Very Much Improved, 2=Much Improved, 3=Minimally Improved, 4=No Change, 5=Minimally Worse, 6=Much Worse, and 7-Very Much Worse." (NCT00314249)
Timeframe: Weeks 1-12 (Visit TX0-TX12) of the stable dose treatment phase
| Intervention | units on scale (Mean) |
|---|
| Placebo | 3.4 |
| Milnacipran | 2.9 |
Change From Baseline in Mean Systolic Blood Pressure /Diastolic Blood Pressure for 12-hour Period Post-AM Dose at Visit 4
Change from baseline to Visit 4 in mean SBP/DBP based on ABPM is defined as the mean SBP/DBP values at Visit 4 minus the corresponding mean SBP/DBP values at baseline in the same 12-hour period post-AM dose. (NCT00618956)
Timeframe: 4 weeks (1 week of dose-escalation, 3 weeks of 100 mg/d)
| Intervention | mm Hg (Mean) |
|---|
| Change in Systolic Blood Pressure | Change in Diastolic Blood Pressure |
|---|
| Milnacipran | 3.8 | 4.2 |
,| Placebo | -0.3 | -0.3 |
Change From Baseline in Mean HR Following 24-hour Treatment at Visit 6
Change from baseline to Visit 6 in HR based on ABPM is defined as the mean HR value at Visit 6 minus the corresponding mean HR value at baseline in the same 24-hour period. (NCT00618956)
Timeframe: 7 weeks (1 week of dose-escalation, 3 weeks of 100 mg/d, followed by 1 week at 150 mg/d and 2 weeks of 200 mg/d)
| Intervention | bpm (Mean) |
|---|
| Change in Heart Rate |
|---|
| Milnacipran | 12.9 |
,| Placebo | -1.6 |
Change From Baseline in Mean Heart Rate (HR) Following 24-hour Treatment at Visit 4
Change from baseline to Visit 4 in HR based on ABPM is defined as the mean HR value at Visit 4 minus the corresponding mean HR value at baseline in the same 24-hour period. (NCT00618956)
Timeframe: 4 weeks (1 week of dose-escalation, 3 weeks of 100 mg/d)
| Intervention | bpm (Mean) |
|---|
| Change in Heart Rate |
|---|
| Milnacipran | 11.7 |
,| Placebo | -1.0 |
Change From Baseline in Mean Systolic Blood Pressure Following 12-hour Period Post-AM Dose at Visit 6
Change from baseline to Visit 6 in mean systolic blood pressure based on ABPM is defined as the mean SBP value at Visit 6 minus the corresponding mean SBP value at baseline in the same 12-hour period post-AM dose. (NCT00618956)
Timeframe: 7 weeks (1 week of dose-escalation, 3 weeks of 100 mg/d, followed by 1 week at 150 mg/d and 2 weeks of 200 mg/d)
| Intervention | mm Hg (Mean) |
|---|
| Change in SBP in Normotensive Patients | Change in SBP in Hypertensive Patients |
|---|
| Milnacipran | 5.5 | 4.4 |
,| Placebo | 0.1 | -0.9 |
Change From Baseline in Mean SBP/DBP Following 12-hour Period Post-AM Dose at Visit 6
Change from baseline to Visit 6 in mean SBP/DBP based on ABPM is defined as the mean SBP/DBP value at Visit 6 minus the corresponding mean SBP/DBP value at baseline in the same 12-hour period post-AM dose. (NCT00618956)
Timeframe: 7 weeks (1 week of dose-escalation, 3 weeks of 100 mg/d, followed by 1 week at 150 mg/d and 2 weeks of 200 mg/d)
| Intervention | mm Hg (Mean) |
|---|
| Change in Systolic Blood Pressure | Change in Diastolic Blood Pressure |
|---|
| Milnacipran | 5.0 | 5.0 |
,| Placebo | -0.4 | -0.5 |
Change From Baseline in Mean Systolic Blood Pressure Following 12-hour Period Post-AM Dose at Visit 4
Change from baseline to Visit 4 in mean systolic blood pressure (SBP) based on ambulatory blood pressure monitor (ABPM) is defined as the mean SBP value at Visit 4 minus the corresponding mean SBP value at baseline in the same 12-hour period post-AM dose. (NCT00618956)
Timeframe: 4 weeks (1 week of dose-escalation, 3 weeks of 100 mg/d)
| Intervention | mm Hg (Mean) |
|---|
| Change in SBP in Normotensive Patients | Change in SBP in Hypertensive Patients |
|---|
| Milnacipran | 4.0 | 3.7 |
,| Placebo | -0.9 | 0.2 |
Change From Baseline in Visual Analog Scale (VAS) 1-week Pain Recall at End of Study
The secondary efficacy measure was the change from Visit 2 (Week 0) in the 1-week pain recall at Visit 6 (Week 11) or End of Study, measured using a 100-mm VAS assessment of pain (0 indicating no pain and 100 indicating the worst possible pain). (NCT00797797)
Timeframe: Baseline (0 weeks) and End of Randomized Treatment Period (11 weeks)
| Intervention | mm (Least Squares Mean) |
|---|
| No Treatment Added | -6.43 |
| Milnacipran Added | -20.77 |
Patient Global Impression of Change (PGIC) Responder Rate at End of Study
"The primary efficacy parameter was the PGIC responder rate, defined as the percentage of patients who rated themselves as very much improved or much improved (ie, having a score of 1 or 2 on the 7-point scale) for the PGIC at end of study (Visit 6 or Early Termination) compared to Visit 1." (NCT00797797)
Timeframe: End of Randomized treatment period (11 weeks)
| Intervention | participants (Number) |
|---|
| Responder | Non-Responder |
|---|
| Milnacipran Added | 83 | 96 |
,| No Treatment Added | 36 | 137 |
Change in Sheehan Disability Scale (SDS) Total Score
The Sheehan Disability Scale (SDS) is a 3-item clinician-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point continuum (0 = no impairment to 10 = most severe) with the total SDS score ranging from 0 (no impairment) to 30 (most severe) (NCT00969150)
Timeframe: From Baseline to Week 8
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Placebo | -8.2 |
| Levomilnacipran ER | -8.8 |
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
"MADRS was used to assess depressive symptomatology during the past week. Patients are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest.~Each item of the 10 items are scored on a 7-point scale. A score of 0 indicates the absence of symptoms,and a score of 6 indicates symptoms of maximum severity. The total MADRS score for this measure ranges from 0 (absence of symptoms) to 60 (maximum severity)." (NCT00969150)
Timeframe: From Baseline to Week 8
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Placebo | -14.2 |
| Levomilnacipran ER | -15.7 |
Change in Sheehan Disability Scale (SDS) Total Score
The Sheehan Disability Scale (SDS) is a 3-item clinician-rated questionnaire used to evaluate functional impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point continuum (0 = no impairment to 10 = most severe) with the total SDS score ranging from 0 (no impairment) to 30 (most severe for all measured symptoms) (NCT00969709)
Timeframe: From Baseline to Week 8
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -7.2 |
| Levomilnacipran ER 40 mg | -8.6 |
| Levomilnacipran ER 80 mg | -9.7 |
| Levomilnacipran ER 120 mg | -9.7 |
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
"The MADRS was used to assess depressive symptomatology during the past week. Patients are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest.~Each item of the 10 items are scored on a 7-point scale. A score of 0 indicates the absence of symptoms,and a score of 6 indicates symptoms of maximum severity. The total MADRS score for this measure ranges from 0 (absence of symptoms) to 60 (maximum severity for all measured symptoms)." (NCT00969709)
Timeframe: From Baseline to Week 8
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Placebo | -11.6 |
| Levomilnacipran ER 40 mg | -14.8 |
| Levomilnacipran ER 80 mg | -15.6 |
| Levomilnacipran ER 120 mg | -16.5 |
Time to Worsening in Multidimensional Assessment of Fatigue (MAF)
Time to worsening in MAF is defined as the time from the first dose of double-blind investigational product to the first visit when a patient has a 10-point increase from baseline in the global index of fatigue in MAF. Scores range from 1 (no fatigue) to 50 (severe fatigue). The MAF contains 16 items measuring 4 dimensions of fatigue: severity, distress, degree of interference in activities of daily living, and timing. Fourteen of the items contain numerical rating scales (increasing in severity); the remaining 2 items have multiple-choice responses (decreasing in severity). (NCT01014585)
Timeframe: From baseline Visit 3 (week 5) to Visit 7 (week 17)
| Intervention | Days (Median) |
|---|
| Responders: Placebo (Milnacipran Withdrawn) | NA |
| Responders: Milnacipran (Milnacipran Continued) | NA |
Time to Worsening in Patient Global Impression of Change (PGIC)
"Time to worsening in Patient Global Impression of Change is defined as the time from the first dose of double-blind investigational product to the first visit when a patient has a PGIC score of 6 or 7. The PGIC is an efficacy assessment on a scale of 1-7 taken at visits 4, 5, 6 and 7. The wording of the assessment is as follows: Since the start of the study, overall my fibromyalgia is: 1=Very Much Improved, 2=Much Improved, 3=Minimally Improved, 4=No Change, 5=Minimally Worse, 6=Much Worse, and 7=Very Much Worse." (NCT01014585)
Timeframe: From baseline Visit 3 (week 5) to Visit 7 (week 17)
| Intervention | Days (Median) |
|---|
| Responders: Placebo (Milnacipran Withdrawn) | 86 |
| Responders: Milnacipran (Milnacipran Continued) | NA |
Time to Loss of Therapeutic Response (LTR)
Time to loss of therapeutic response is defined as the time from the first dose of double-blind investigational product to the first visit when a patient has a < 30% reduction in Visual Analog Scale (VAS) pain score from pre-milnacipran exposure OR a worsening of fibromyalgia requiring, in the judgment of the investigator, an alternative treatment (NCT01014585)
Timeframe: From baseline Visit 3 (week 5) to Visit 7 (week 17)
| Intervention | Days (Median) |
|---|
| Responders: Placebo (Milnacipran Withdrawn) | 56 |
| Responders: Milnacipran (Milnacipran Continued) | NA |
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
"MADRS was used to assess depressive symptomatology during the past week. Patients are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest.~Each item of the 10 items are scored on a 7-point scale. A score of 0 indicates the absence of symptoms,and a score of 6 indicates symptoms of maximum severity. The total MADRS score for this measure ranges from 0 (absence of symptoms) to 60 (maximum severity)." (NCT01034462)
Timeframe: From Baseline to Week 8
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Placebo | -12.2 |
| Levomilnacipran ER | -15.3 |
Change in Sheehan Disability Scale (SDS) Total Score
The Sheehan Disability Scale (SDS) is a 3-item clinician-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point continuum (0 = no impairment to 10 = most severe) with the total SDS score ranging from 0 (no impairment) to 30 (most severe) (NCT01034462)
Timeframe: From Baseline to Week 8
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Placebo | -5.4 |
| Levomilnacipran ER | -8.0 |
Identification of Group Assignment
Subjects identifying group assignment correctly (NCT01038323)
Timeframe: week 21
| Intervention | participants (Number) |
|---|
| Combination | 0 |
| Milnacipran | 0 |
| Cognitive Behavioral Therapy | 0 |
Change in Evoked Pain Scores
0 to 20 pain scale, with higher pain score representing greater sensitivity to pressure pain stimuli (NCT01038323)
Timeframe: Baseline and Week 21 clinic visits
| Intervention | units on a scale (Mean) |
|---|
| Combination | -0.76 |
| Milnacipran | -0.41 |
| Cognitive Behavioral Therapy | 0.78 |
Change in Weekly Average Pain Intensity
Change in weekly average pain intensity score from baseline to week 21 (scale from -10 to +10; the more negative the value, the better in terms of pain reduction) (NCT01038323)
Timeframe: Baseline and Week 21clinic visits
| Intervention | units on a scale (Mean) |
|---|
| Combination | -2.1 |
| Milnacipran | -0.97 |
| Cognitive Behavioral Therapy | -1.67 |
Responder Status Based on Patient Global Impression of Change (PGIC) Score at Visit 5 (Week 13)
The PGIC is a patient-reported measure of improvement in pain sensation and quality of life scored on a scale from 1 (very much improved) to 7 (very much worse). To meet the criteria for a responder in this study, patients must report a score of 1 (very much improved) or 2 (much improved) on the PGIC. (NCT01077375)
Timeframe: Assessed at Visit 4 (Week 9) and Visit 5 (Week 13) or early termination. Presented results generated via LOCF approach.
| Intervention | participants (Number) |
|---|
| Placebo | 5 |
| Milnacipran | 26 |
Change From Baseline to Visit 5 (Week 13) in the Visual Analog Scale (VAS) 1-week Pain Recall Score
The VAS assessment ranges from a scale of 0 (no pain) to 100 (worst possible pain). (NCT01077375)
Timeframe: Change from Baseline (Week 3) to Visit 5 (Week 13)
| Intervention | Units on a scale (Mean) |
|---|
| Placebo | -1.3 |
| Milnacipran | -12.3 |
Time to Relapse (Days)
Number of days until patients meet relapse criteria. Relapse was defined as 1 or more of the following: 1. MADRS total score of at least 22 at 2 consecutive visits 2. Increase of 2 or more points in CGI-I score compared with the CGI-I score at Visit 9 at 2 consecutive visits 3. Premature discontinuation due to insufficient therapeutic response 4. MADRS item 10 score of at least 4 (NCT01085812)
Timeframe: 24 Weeks
| Intervention | Days (Mean) |
|---|
| Placebo | NA |
| Levomilnacipran ER | NA |
Change in Cognitive Function Assessed by the no Cue Condition of the Attention Network Test (ANT).
The Attention Network Test (ANT) is a computerized test designed to evaluate the efficiency of the attention network. The ANT consists of a set of cued reaction time tasks to assess vigilance and efficiency to detect novel visual stimuli. The ANT also includes a set of flanker tasks during which a decision needs to be made about whether the orientation of a central stimulus is congruent or incongruent with a set of flanking arrows. Scores on the cued reaction time tasks (no cue, centre cue, double cue) reflect latency to respond measured in milliseconds (slower performance equals greater values). The score on the flanker task reflecting executive attention is derived by subtracting obtained latencies on the congruent flanker from the incongruent condition. Based on our prior work, we are hypothesizing that drug treated Ss will show improved performance on the no cue reaction time condition and on the derived executive attention variable compared to placebo treated. (NCT01108731)
Timeframe: Baseline and 2 months
| Intervention | latency to respond (msecs.) (Mean) |
|---|
| No cue condition | Executive attention |
|---|
| Patients Taking the Drug Minalcipran | -79.56 | -68.73 |
,| Patients Taking the Placebo | -35.00 | -34.77 |
Change in Widespread Pain
Pain was assessed using a visual analog scale (VAS) ranging from 0 (no pain) to 10 (worst pain ever). The baseline value recorded was widespread pain at the time of assessment and the 2 months follow value recorded was widespread pain over the week prior to assessment. (NCT01108731)
Timeframe: 2 months
| Intervention | units on a scale (Mean) |
|---|
| Patients Taking the Drug Minalcipran | -1.24 |
| Patients Taking the Placebo | 0.66 |
Change in Ventricular Lactate Levels in the Brain
Ventricular lactate levels will be assessed before and at the end of the trial using a scanning method known as magnetic resonance spectroscopy (MRS), which is used to determine the presence and quantity of a number of chemicals in the brain. (NCT01108731)
Timeframe: Baseline and 2 months
| Intervention | international units (iu) (Mean) |
|---|
| Patients Taking the Drug Minalcipran | -0.87 |
| Patients Taking the Placebo | 0.32 |
Diffuse Noxious Inhibitory Control (DNIC) Effect at Baseline.
0-100 numerical rating scale. 0 on the numerical scale represents a better outcome. 100 represents a worse outcome. (NCT01173055)
Timeframe: Baselines measured at week 0 and week 9 after washout from first assignment to treatment
| Intervention | units on a scale (Mean) |
|---|
| Milnacipran | 8.134 |
| Placebo | 12.0240 |
Change in Pain Tolerance From Baseline to End of Treatment
The primary outcome parameter is the change in pressure pain tolerance (maximum tolerated pressure) from baseline to end of treatment. Measured in kg/cm^2. Lower values represent a worse outcome. (NCT01173055)
Timeframe: baseline compared wtih 6 weeks of treatment
| Intervention | kg/cm^2 (Mean) |
|---|
| Pre-Treatment (Week 0 or 9) | Post-Treatment (Week 6 or 15) |
|---|
| Milnacipran | 4.2667 | 3.8667 |
,| Placebo | 3.80 | 3.8667 |
Pain Tolerance at Baseline
The primary outcome parameter is the pressure pain tolerance (maximum tolerated pressure) at pre-treatment baseline. (NCT01173055)
Timeframe: Baselines measured at week 0 and week 9 after washout from first assignment to treatment
| Intervention | kg/cm^2 (Mean) |
|---|
| Milnacipran | 4.2667 |
| Placebo | 3.80 |
Pain Threshold at Baseline
The primary outcome parameter is the medium pressure pain threshold at pre-treatment baseline (pressure that evokes a perceived pain intensity of 40-50 out of 100 on a numerical rating scale). Measured in kg/cm^2. (NCT01173055)
Timeframe: Baselines measured at week 0 and week 9 after washout from first assignment to treatment
| Intervention | kg/cm^2 (Mean) |
|---|
| Milnacipran | 2.7333 |
| Placebo | 2.583 |
Change in Diffuse Noxious Inhibitory Control (DNIC) Effect From Baseline to End of Treatment.
0-100 numerical rating scale. 0 on the numerical scale represents a better outcome. 100 represents a worse outcome. (NCT01173055)
Timeframe: baseline compared with 6 weeks of treatment
| Intervention | units on a scale (Mean) |
|---|
| Pre-Treatment (Week 0 or 9) | Post-Treatment (Week 6 or 15) |
|---|
| Milnacipran | 8.134 | 11.0355 |
,| Placebo | 12.0240 | 8.50 |
Change in Pain Threshold From Baseline to End of Treatment.
The primary outcome parameter is the change in medium pressure pain threshold (pressure that evokes a perceived pain intensity of 40-50 out of 100 on a numerical rating scale) from baseline to end of treatment. Measured in kg/cm^2. Lower values represent a worse outcome. (NCT01173055)
Timeframe: baseline compared with 6 weeks of treatment
| Intervention | kg/cm^2 (Mean) |
|---|
| Pre-Treatment (Week 0 or 9) | Post-Treatment (Week 6 or 15) |
|---|
| Milnacipran | 2.7333 | 2.650 |
,| Placebo | 2.583 | 2.70 |
Change in Conditioned Pain Modulation (CPM)
CPM is defined as the difference between pain threshold A (measured after a conditioning stimulus activates pathways that inhibit pain) and pain threshold B (measured before the conditioning stimulus is applied). The conditioning stimulus was immersion of the hand in a cold water bath. Pressure pain threshold was assessed at the trapezius muscle initially. Subjects were then instructed to immerse their hand in a water bath for 30 seconds. At 20 seconds, pressure pain threshold at the trapezius was assessed again. We defined the magnitude of subjects' CPM as the difference in pressure pain threshold between baseline and 20 seconds after cold water immersion. This difference was compared to that measured at 6 weeks. The scale for the difference in CPM ranged from 0-11 kg/cm^2, with 0 indicating no change in CPM between 6 weeks and baseline and 11 indicating the maximum possible change. A greater change in CPM between baseline and 6 weeks is indicative of improvements in CPM. (NCT01207453)
Timeframe: Baseline to 6 weeks
| Intervention | kg/cm^2 (Mean) |
|---|
| Baseline | 6 Weeks | Change |
|---|
| Milnacipran | 0.8 | 0.9 | 0.1 |
,| Placebo | 0.8 | 0.9 | 0.1 |
Knee Pain Threshold
A measure of the change in knee pain threshold from baseline to 6 weeks. Knee pain threshold was determined by applying pressure to a subject's knee until the subject felt pain. The difference between the average knee pain threshold (an average for the right and left knees) at baseline was compared to that at 6 months. Pain threshold was measured in kg/cm^2. The difference in threshold could range from 0-11 kg/cm^2. A higher difference between thresholds indicates improved pain sensitivity. (NCT01207453)
Timeframe: Baseline to 6 weeks
| Intervention | kg/cm^2 (Mean) |
|---|
| Baseline | 6 weeks | Change |
|---|
| Milnacipran | 6.9 | 7.3 | 0.3 |
,| Placebo | 7.0 | 7.3 | 0.3 |
Symptom Intensity Scale (SIS)
A measure of the change in SIS score from baseline to 6 weeks. The SIS score ranges from 0-9.75, with high scores being worse indicating more widespread pain and fatigue. (NCT01207453)
Timeframe: Baseline to 6 weeks
| Intervention | units on a scale (Mean) |
|---|
| Baseline | 6 weeks | Change |
|---|
| Milnacipran | 5.2 | 4.5 | -0.7 |
,| Placebo | 5.1 | 4.3 | -0.8 |
Thumbnail Pain Threshold
A measure of the change in thumbnail pain threshold from baseline to 6 weeks. Thumbnail pain threshold was determined by applying pressure to a subjectt's thumbnail until the subject felt pain. The difference between the average thumbnail pain threshold (an average for the right and left thumbs) at baseline was compared to that at 6 months. Pain threshold was measured in kg/cm^2. The difference in threshold could range from 0-11 kg/cm^2. A higher difference between thresholds indicates improved pain sensitivity. (NCT01207453)
Timeframe: Baseline to 6 weeks
| Intervention | kg/cm^2 (Mean) |
|---|
| Baseline | 6 weeks | Change |
|---|
| Milnacipran | 5.3 | 6.0 | 0.7 |
,| Placebo | 5.8 | 5.8 | -0.02 |
Trapezius Pain Threshold
A measure of the change in trapezius pain threshold from baseline to 6 weeks. Trapezius pain threshold was determined by applying pressure to a subject's trapezius muscle until the subject felt pain. The difference between the average trapezius pain threshold (an average for the right and left trapezii) at baseline was compared to that at 6 months. Pain threshold was measured in kg/cm^2. The difference in threshold could range from 0-11 kg/cm^2. A higher difference between thresholds indicates improved pain sensitivity. (NCT01207453)
Timeframe: Baseline to 6 weeks
| Intervention | kg/cm^2 (Mean) |
|---|
| Baseline | 6 Weeks | Change |
|---|
| Milnacipran | 5.1 | 5.5 | 0.4 |
,| Placebo | 4.9 | 5.5 | 0.6 |
Brief Pain Inventory (BPI) Change
"A measure of change in scores on the BPI short form, a 24-hr average pain item, from baseline to 6 weeks, The BPI short form scores ranges from 0-10, with 10 being the worst pain." (NCT01207453)
Timeframe: Baseline to 6 weeks
| Intervention | units on a scale (Mean) |
|---|
| Baseline | 6 weeks | Change |
|---|
| Milnacipran | 5.6 | 4.8 | -0.7 |
,| Placebo | 5.2 | 4.9 | -0.3 |
Wrist Pain Threshold
A measure of the change in wrist pain threshold from baseline to 6 weeks. Wrist pain threshold was determined by applying pressure to a subject's wrist until the subject felt pain. The difference between the average wrist pain threshold (an average for the right and left wrists) at baseline was compared to that at 6 months. Pain threshold was measured in kg/cm^2. The difference in threshold could range from 0-11 kg/cm^2. A higher difference between thresholds indicates improved pain sensitivity. (NCT01207453)
Timeframe: Baseline to 6 weeks
| Intervention | kg/cm^2 (Mean) |
|---|
| Baseline | 6 weeks | Change |
|---|
| Milnacipran | 5.0 | 5.9 | 0.9 |
,| Placebo | 5.3 | 5.9 | 0.6 |
Effect Size of VAS Pain
"Effect size (ES) calculation for VAS pain between milnacipran and placebo groups' ES is dimensionless; Visual analogue scale (VAS) measured pain in integral units from 0 (low end) to 100 (high end); ES (Cohen's d) is a well described statistical construct and is calculated from the difference between the means (determined at baseline and 6 weeks here) divided by the pooled standard deviation.~This is the primary outcome measure." (NCT01225068)
Timeframe: 6 weeks from baseline
| Intervention | units on a scale (Mean) |
|---|
| Placebo | 24.8 |
| Milnacipran | 31.3 |
Profile of Mood States (POMS)
Depressive 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). (NCT01225991)
Timeframe: Week 1 and 12
| Intervention | units on a scale (Mean) |
|---|
| POMS Anxiety Week 1 | POMS Depression Week 1 | POMS Vigor Week 1 | POMS Fatigue Week 1 | POMS Friendliness Week 1 | POMS Anxiety Week 12 | POMS Depression Week 12 | POMS Vigor Week 12 | POMS Fatigue Week 12 | POMS Friendliness Week 12 |
|---|
| Milnacipran, Active Drug, Open-label | 5.75 | 4.08 | 13.00 | 6.67 | 6.42 | 5.50 | 3.92 | 16.83 | 6.00 | 9.42 |
Visual Analogue Scale to Evaluate Fatigue (VAS-F)
The 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. (NCT01225991)
Timeframe: Change scores from Week 1 to Week 12 of energy and fatigue
| Intervention | units on a scale (Mean) |
|---|
| Fatigue Subscale | Energy Subscale |
|---|
| Milnacipran, Active Drug, Open-label | 15.2 | 3.7 |
Connor-Davidson Resilience Scale (CD-RISC)
Resilience: 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. (NCT01225991)
Timeframe: Change Scores from Week 1 to Week 12
| Intervention | units on a scale (Mean) |
|---|
| Milnacipran, Active Drug, Open-label | -2.2 |
Pain Rating Index
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. (NCT01225991)
Timeframe: Change score at baseline and 12 weeks
| Intervention | units on a scale (Mean) |
|---|
| Milnacipran, Active Drug, Open-label | -3.7 |
(UKU) Side Effects Rating Scale Profile
The UKU assessment will rate the number of participants with emerging adverse events. (NCT01225991)
Timeframe: Weeks 1-4, 6, 8, 10, 12
| Intervention | Participants (Count of Participants) |
|---|
| Concentration difficulties | Asthenia / Lassitude / Increased Fatiguability | Sleepiness / Sedation | Failing Memory | Depression | Reduced Duration of Sleep | Nausea / Vomiting | Micturition Disturbances | Increased Tendency to Sweating | Ejaculatory Dysfunction | Tension Headache |
|---|
| Milnacipran, Active Drug, Open-label | 1 | 6 | 2 | 1 | 2 | 1 | 3 | 2 | 3 | 1 | 2 |
Slow Wave Sleep (SWS)
Time spent in stage 3 of non-rapid eye movement sleep and often referred to as deep sleep. (NCT01234675)
Timeframe: 4-Week treatment with milnacipran and placebo
| Intervention | percentage of total sleep time (Mean) |
|---|
| Milnacipran | 8.4 |
| Placebo | 9.4 |
Wake After Sleep Onset (WASO)
Wake time after defined sleep onset until lights on. (NCT01234675)
Timeframe: 4-Week maintenance treatment with milnacipran and placebo
| Intervention | minutes (Mean) |
|---|
| Milnacipran | 76.2 |
| Placebo | 53.6 |
Brief Pain Inventory (BPI) Mean Severity Score
"The score is derived from the BPI scale and measures pain intensity in the past 24 hour. The pain severity score is derived as the average score of 4 pain items assessing pain at its worst, least, average and now and ranges from 0-10 with higher scores reflecting greater pain" (NCT01234675)
Timeframe: 4-Week treatment with milnacipran and placebo
| Intervention | score on a scale (Mean) |
|---|
| Milnacipran | 4.1 |
| Placebo | 4.7 |
Arousal Index (AI)
Number of arousals per hour of sleep (NCT01234675)
Timeframe: 4-Week treatment with milnacipran and placebo
| Intervention | arousals per hour (Mean) |
|---|
| Milnacipran | 30.2 |
| Placebo | 31.2 |
Brief Pain Inventory (BPI) Mean Interference Score
The score is derived from the BPI scale and measures the effect of pain on functioning in the past 24 hour. It is the average score of 7 items interfering with general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life. Score ranges from 0-10 with higher scores reflecting greater interference. (NCT01234675)
Timeframe: 4-Week treatment with milnacipran and placebo
| Intervention | score on a scale (Mean) |
|---|
| Milnacipran | 3.8 |
| Placebo | 4.3 |
Fatigue Severity Scale (FSS) Total Score
The scale is a 9-item self-report of fatigue in the past week and scored on a 7-point scale with 1 = strongly disagree and 7 = strongly agree. Scores range from 9 to 63 with higher scores indicating higher fatigue severity. A total score greater or equal to 36 suggests fatigue. (NCT01234675)
Timeframe: 4-Week treatment with milnacipran and placebo
| Intervention | score on a scale (Mean) |
|---|
| Milnacipran | 41.0 |
| Placebo | 42.3 |
Fibromyalgia Impact Questionnaire (FIQ) Total Score
The scale is composed of 10 items relating to fibromyalgia symptoms experienced in the past week. Score ranges from 0 to 100 with higher scores indicating a greater effect of fibromyalgia on a person's life. (NCT01234675)
Timeframe: 4-Week treatment with milnacipran and placebo
| Intervention | score on a scale (Mean) |
|---|
| Milnacipran | 40.0 |
| Placebo | 45.3 |
Latency to Persistent Sleep Onset (LPS)
It is defined as time from lights out to the first consecutive 2 minutes of uninterrupted sleep. (NCT01234675)
Timeframe: 4-Week treatment with milnacipran and placebo
| Intervention | minutes (Mean) |
|---|
| Milnacipran | 41.6 |
| Placebo | 38.6 |
Number of Awakenings After Sleep Onset (NAASO)
Number of awakenings after defined sleep onset until lights on. (NCT01234675)
Timeframe: 4-Week maintenance treatment with milnacipran and placebo
| Intervention | Awakenings (Mean) |
|---|
| Milnacipran | 39.5 |
| Placebo | 34.9 |
Total Sleep Time (TST)
Total sleep of all Rapid Eye Movement (REM) and Non- Rapid Eye Movement Sleep (NTREM) from lights out to lights on. (NCT01234675)
Timeframe: 4-Week treatment with milnacipran and placebo
| Intervention | minutes (Mean) |
|---|
| Milnacipran | 361.7 |
| Placebo | 386.1 |
Sleep Efficiency (SE)
Percentage of time spent asleep while in bed (NCT01234675)
Timeframe: 4-Week maintenance treatment with milnacipran and placebo
| Intervention | percentage of total sleep time (Mean) |
|---|
| Milnacipran | 77.1 |
| Placebo | 83.3 |
Sleep Problem Index 2, Medical Outcomes Study Sleep Scale (MOS-SS)
This is a subjective index derived from the medical outcomes study sleep scale (MOS-SS) scored on a 0-100 possible range with higher scores indicating more severe sleep disruption. The scale is a self-report instrument consisting of 12 items that assess perceived initiation and maintenance of sleep, respiratory problems during sleep, sleep duration, perceived adequacy of sleep and daytime somnolence. (NCT01234675)
Timeframe: 4-Week treatment with milnacipran and placebo
| Intervention | score on a scale (Mean) |
|---|
| Milnacipran | 37.8 |
| Placebo | 34.9 |
Sleep Quality Scale
"Sleep quality measure derived from daily sleep diary rating ranging from 0 (very poor) to 10 (excellent)" (NCT01234675)
Timeframe: 4-Week treatment with milnacipran and placebo
| Intervention | score on a scale (Mean) |
|---|
| Milnacipran | 5.2 |
| Placebo | 4.9 |
Change in Clinical Global Impression of Severity (CGI-S) for Fatigue Score
The CGI-S is a clinician-rated scale that rates the severity of the patient's current state of fatigue based on the Investigator's clinical opinion with regard to the patient population with Major Depressive Disorder (MDD). Patient were rated on a scale from 1 to 7, with 1 indicating a normal state and 7 indicating that the patient was among the most extremely fatigued (NCT01254305)
Timeframe: From Baseline to Week 8
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -1.5 |
| Levomilnacipran ER | -1.8 |
| SSRI | -1.9 |
Change in Cognitive and Physical Functioning Questionnaire (CPFQ), Last Observation Carried Forward
The Cognitive and Physical Functioning Questionnaire is a patient-rated, 7-item scale used to measure cognitive and executive dysfunction in mood and anxiety disorders. The CPFQ is sensitive to change with treatment and displays convergent validity by significant correlations with other measures of sleepiness, fatigue, apathy, and neuropsychological functioning. Patients are rated on a scale from 1 to 6 for seven common complaints of depressed patients reporting fatigue or cognitive/executive problems-with 1 indicating greater than normal functioning, 2 indicating normal functioning, and 3 to 6 indicating degrees of impaired functioning. The CPFQ ranges from the best possible score of 7 (greater than normal functioning) to the worst possible score of 42 (totally absent). (NCT01254305)
Timeframe: From Baseline to Week 8
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -5.9 |
| Levomilnacipran ER | -7.0 |
| SSRI | -6.4 |
Change in Patient Global Impressions of Severity (PGI-S) for Fatigue Score
The PGI-S is a clinician-rated scale that rates was used to rate the severity of the patient's current state of overall fatigue. Patients were rated on a scale from 1 to 7, with 1 indicating no symptoms of fatigue and 7 indicating extreme fatigue. (NCT01254305)
Timeframe: From Baseline to Week 8
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -1.4 |
| Levomilnacipran ER | -1.7 |
| SSRI | -1.7 |
Likert Pain Scale Score
"The Likert Pain Scale Score is a psychometric scale commonly involved in research that employs questionnaires to measure the intensity of pain. It is used to determine the level of pain for research participants. The minimum score of 0 indicates no pain which is the better score and the maximum and total score of 10 indicates the the worst possible pain which is the worse outcome . Scores 1-3= Mild, scores 4-6= Moderate, scores 7-10= Severe. It is the most widely used approach to scaling responses in survey research. Patients will fill out a pain diary from baseline to end of treatment. This will be used to assess if there was a reduction in pain of the daily averaged weekly 0-10 pain scale at week 9 compared to the baseline. The Unit of Measure is the scores on the scale." (NCT01288937)
Timeframe: Baseline, 9 weeks
| Intervention | Scores on a scale (Mean) |
|---|
| Baseline | 9 Weeks |
|---|
| Milnacipran | 5.6 | 3.2 |
,| Placebo | 7.15 | 5.15 |
24-hour Vulvar Pain
"0 equals no vulvar pain within the last 24 hours to 10 equals worse imaginable vulvar pain within the last 24 hours. This measure was used to measure mean values at baseline and at 18 weeks post-treatment." (NCT01304589)
Timeframe: 18 weeks
| Intervention | units on a scale (Mean) |
|---|
| Milnacipram | 0.73 |
Coital Pain
"0 equals no pain with intercourse to 10 equals worse imaginable pain with intercourse. This measure was used to measure mean values at baseline and at 18 weeks post-treatment." (NCT01304589)
Timeframe: 18 weeks
| Intervention | units on a scale (Mean) |
|---|
| Milnacipram | 3.43 |
Pain Rating Index
"The Pain Rating Index is a component of the McGill Pain Questionnaire which measures sensory and affective components of pain. 0 equals no pain to 45 equals severe pain. This measure was used to measure mean values at baseline and at 18 weeks post-treatment." (NCT01304589)
Timeframe: 18 weeks
| Intervention | units on a scale (Mean) |
|---|
| Milnacipram | 12.3 |
Tampon Pain
"0 equals no pain with tampon insertion to 10 equals worse pain imaginable with tampon insertion. This measure was used to measure mean values at baseline and at 18 weeks post-treatment." (NCT01304589)
Timeframe: 18 weeks
| Intervention | units on a scale (Mean) |
|---|
| Milnacipran | 2.45 |
Time to First Loss of Therapeutic Response (LTR) Following Randomization to Milnacipran or Placebo.
During the open-label period, 20 patients out of 116 enrolled had a reduction from baseline (Visit 2) of at least 50% in their pain, were classified as responders and were randomized (Visit 7). A Loss of Therapeutic Response was said to occur if, during the double-blind treatment period, any of the following occurred: • A worsening of fibromyalgia requiring an alternate treatment OR • An increase in 1-week mean of daily pain ratings (11-point numeric rating scale) to greater than 70% of Baseline (Visit 2) OR • Withdrawal from the study for any reason except withdrawals due to extenuating circumstances (NCT01328002)
Timeframe: Change from Visit 7 (Week 8) to Visit 10 (Week 16)
| Intervention | Days (Mean) |
|---|
| Placebo | NA |
| Milnacipran | 7.0 |
Patient Global Impression of Severity (PGIS)
"The wording of the PGIS assessment was as follows: Considering all aspects of your illness, how do you evaluate the severity of your fibromyalgia? The possible responses to this question were 1. Normal, not at all ill 2. Borderline ill 3. Mildly ill 4. Moderately ill 5. Severely ill 6. Extremely ill" (NCT01328002)
Timeframe: Change from Visit 7 (Week 8) to Visit 10 (Week 16)
| Intervention | units on a scale (Mean) |
|---|
| Placebo | 0.5 |
| Milnacipran | 0.4 |
Number of Patients Who Experienced Any Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS)
"The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal behaviors as defined by the eC-SSRS are:~Preparatory acts or behavior~Aborted attempt~Interrupted attempt~Actual attempt~Completed suicide attempt" (NCT01331109)
Timeframe: Baseline (Visit 1) to Week 53 (Visit 9)
| Intervention | participants (Number) |
|---|
| Milnacipran | 0 |
Number of Patients Who Experienced Level 1 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS).
"The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal ideation is assessed at 5 distinct levels of increasing severity:~Level 1: Wish to be Dead~Level 2: Non-Specific Active Suicidal Thoughts~Level 3: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act~Level 4: Active Suicidal Ideation with Some Intent to Act, without Specific Plan~Level 5: Active Suicidal Ideation with Specific Plan and Intent" (NCT01331109)
Timeframe: Baseline (Visit 1) to Week 53 (Visit 9)
| Intervention | participants (Number) |
|---|
| Milnacipran | 3 |
Number of Patients Who Experienced Level 2 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS).
"The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal ideation is assessed at 5 distinct levels of increasing severity:~Level 1: Wish to be Dead~Level 2: Non-Specific Active Suicidal Thoughts~Level 3: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act~Level 4: Active Suicidal Ideation with Some Intent to Act, without Specific Plan~Level 5: Active Suicidal Ideation with Specific Plan and Intent" (NCT01331109)
Timeframe: Baseline (Visit 1) to Week 53 (Visit 9)
| Intervention | participants (Number) |
|---|
| Milnacipran | 0 |
Number of Patients Who Experienced Level 3 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS).
"The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal ideation is assessed at 5 distinct levels of increasing severity:~Level 1: Wish to be Dead~Level 2: Non-Specific Active Suicidal Thoughts~Level 3: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act~Level 4: Active Suicidal Ideation with Some Intent to Act, without Specific Plan~Level 5: Active Suicidal Ideation with Specific Plan and Intent" (NCT01331109)
Timeframe: Baseline (Visit 1) to Week 53 (Visit 9)
| Intervention | participants (Number) |
|---|
| Milnacipran | 1 |
Number of Patients Who Experienced Level 4 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS).
"The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal ideation is assessed at 5 distinct levels of increasing severity:~Level 1: Wish to be Dead~Level 2: Non-Specific Active Suicidal Thoughts~Level 3: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act~Level 4: Active Suicidal Ideation with Some Intent to Act, without Specific Plan~Level 5: Active Suicidal Ideation with Specific Plan and Intent" (NCT01331109)
Timeframe: Baseline (Visit 1) to Week 53 (Visit 9)
| Intervention | participants (Number) |
|---|
| Milnacipran | 1 |
Number of Patients Who Experienced Level 5 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS).
"The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal ideation is assessed at 5 distinct levels of increasing severity:~Level 1: Wish to be Dead~Level 2: Non-Specific Active Suicidal Thoughts~Level 3: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act~Level 4: Active Suicidal Ideation with Some Intent to Act, without Specific Plan~Level 5: Active Suicidal Ideation with Specific Plan and Intent" (NCT01331109)
Timeframe: Baseline (Visit 1) to Week 53 (Visit 9)
| Intervention | participants (Number) |
|---|
| Milnacipran | 0 |
Adverse Events
Number of Patients who experience one or more treatment emergent adverse event (TEAE) (NCT01331109)
Timeframe: Baseline (Visit 1) to Week 53 (Visit 9)
| Intervention | participants (Number) |
|---|
| Milnacipran | 42 |
Change in Diagnostic Analysis of Nonverbal Activity-2 ADULT FACIAL EXPRESSIONS: (DANVA2-AF)
"This scale is shown to be sensitive to change in adults with autism, and related to amygdala function. Higher scores mean a better outcome.A clinical tool measuring emotion recognition through facial expression, voice and posture.~Child faces 2 (range 0 - 100, higher values reflecting higher % of errors)~Adult faces 2 (range 0 - 100, higher values reflecting higher % of errors)~Child paralanguage 2 (range 0 - 100, higher values reflecting higher % of errors)~Adult paralanguage 2 (range 0 - 100, higher values reflecting higher % of errors) Errors are counted and organized by pre-determined affect and intensity. Subtests considered separately." (NCT01337700)
Timeframe: baseline, weeks 2,4,6,8,10,12
| Intervention | score on a scale (Mean) |
|---|
| Baseline | Week 2 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 |
|---|
| Milnacipran | 16.5 | 19.25 | 19.6 | 19.4 | 17 | 17.25 | 18 |
,| Placebo | 18.5 | 19 | 19.6 | 20 | 19.2 | 20 | 18.8 |
Change in Hyperactivity as Measured by Aberrant Behavior Checklist - Hyperactivity Scale
"The Aberrant Behavior Checklist is an informant-based questionnaire consisting of 58 items subdivided amongst 5 scales: irritability, lethargy and social withdrawal, stereotypic behavior, hyperactivity/non-compliance, and inappropriate speech [34]. A score for each item ranges from 0 indicating no problem to 3 indicating severe problem. Scale scores are calculated by summing the items within that scale. Higher scores indicate greater impairment.Reported Data is for change in ABC-H from baseline to endpoint (week 0 to week 12).This data is specifically looking at the hyperactivity scale which is 16 items with each item ranging from 0-3 making total scores 0-48." (NCT01337700)
Timeframe: Baseline to Endpoint - 12 weeks
| Intervention | units on a scale (Mean) |
|---|
| Milnacipran | -10.4 |
| Placebo | -4.2 |
Change in Autism Severity Levels Based on the Clinical Global Impressions Scale
The CGI-I reflects the rater's impression of the subject's current autism severity on a 7-point scale ranging from Much Improved (1) to Much worse (5). (NCT01337700)
Timeframe: screening, baseline, weeks 2,4,6,8,10,12
| Intervention | Participants (Count of Participants) |
|---|
| Much Improved | Minimally Improved | No Change | Minimally Worse | Much Worse |
|---|
| Milnacipran | 1 | 1 | 3 | 0 | 0 |
,| Placebo | 1 | 1 | 2 | 1 | 0 |
Change in Repetitive Behaviors Using YBOCS-Compulsion and Rigidity Subscale
"This scale has been shown to be a sensitive outcome measure in autism trials of repetitive behaviors. Data for secondary outcome not analyzed due to lack of significance in primary outcomes measured.~scale range: 0 - 40 total, 0 - 7 subclinical, 8-15 mild, 16 - 23 moderate, 24 - 31 severe, 32 - 40 extreme~score interpretation: Higher overall scores reflect increasing symptom severity." (NCT01337700)
Timeframe: baseline, weeks 2,4,6,8,10,12
| Intervention | score on a scale (Mean) |
|---|
| Baseline | Week 2 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 |
|---|
| Milnacipran | 12.2 | 10 | 11.6 | 11.8 | 10.4 | 11.6 | 12.4 |
,| Placebo | 12 | 12.2 | 13.2 | 12 | 9.8 | 12.8 | 12 |
Change in Score on Conners Adults Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale
"Change will be measured in each subject's score on the Conners Adults Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale from baseline through study end (week 12).Higher values represent a worse outcome.~The raw scores are converted to T-scores for each scale and sub-scale which are then compared against the mean. Higher values represent a worse outcome. A T-score of 50 is the mean of a relevant reference population. A T-score above 65 indicates a moderate to severe problem. For example, Row 1 is the mean of baseline T-scores for the Inattention/ Memory subscale and Row 2 is the mean of week 12 T-scores for the Inattention/ Memory subscale. The difference between these two means is used to measure the change from baseline through week 12 for both the groups." (NCT01337700)
Timeframe: Baseline and Week 12 scores
| Intervention | T-score (Mean) |
|---|
| Baseline: T-SCORES- Inattention/Memory | Week 12: T-SCORES- Inattention/Memory | Baseline: T-SCORES- Hyperactivity/Restlessness | Week 12:T-SCORES -Hyperactivity/Restlessness | Baseline: T-SCORES- Impulsivity/Emotional Lability | Week 12: T-SCORES- Impulsivity/Emotional Lability |
|---|
| Milnacipran | 68.6 | 53.4 | 55 | 44.8 | 55.2 | 47.8 |
,| Placebo | 71.8 | 57 | 50.8 | 39.8 | 49.2 | 43.6 |
Change in Sheehan Disability Scale (SDS) Total Score
The Sheehan Disability Scale (SDS) is a 3-item clinician-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point continuum (0 = no impairment to 10 = most severe) with the total SDS score ranging from 0 (no impairment) to 30 (most severe) (NCT01377194)
Timeframe: From Baseline to Week 8
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Placebo | -5.4 |
| Levomilnacipran ER 40 mg | -7.3 |
| Levomilnacipran ER 80 mg | -8.2 |
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score - Mixed-effects Model for Repeated Measures (MMRM) Analysis.
The Montgomery-Asberg Depression Rating Scale (MADRS) rates patients on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest. Each item was scored on a 7-point scale. A score of 0 indicated the absence of symptoms, and a score of 6 indicated symptoms of maximum severity. The minimum overall score possible was 0 (absence of symptoms), with a maximum overall score of 60 (maximum severity). (NCT01377194)
Timeframe: From Baseline to Week 8
| Intervention | Units on a scale (Mean) |
|---|
| Placebo | -11.3 |
| Levomilnacipran ER 40 mg | -14.6 |
| Levomilnacipran ER 80 mg | -14.4 |
Change in Days With Non-Migraine Headache Per Month From Baseline to 90 Days
"On days where the patient indicated they had a headache, patients were instructed to complete the diary questions regarding headache characteristics using International Headache Classification Diagnostics. This was information was used to calculate non-migraine headache days days per month. Days with migraine over a 30 day period were summed to generate a number for each time frame (baseline and 90 days). For the outcome measure, higher positive numbers indicate higher reduction of days with non-migraine headache.~Change in days with non-migraine headache = Score[Baseline] - Score[90 days]" (NCT01393522)
Timeframe: Baseline and 90 days
| Intervention | Days per Month (Mean) |
|---|
| Milnacipran | 2.35 |
| Placebo | 0.76 |
Change in Days With Migraine Per Month From Baseline to 90 Days
"On days where the patient indicated they had a headache, patients were instructed to complete the diary questions regarding headache characteristics using International Headache Classification Diagnostics. This information was used to calculate migraine days per month. Days with migraine over a 30 day period were summed to generate a number for each time frame (baseline and 90 days). For the outcome measure, higher positive numbers indicate higher reduction of days with migraine.~Change in days with migraine = Score[Baseline] - Score[90days]" (NCT01393522)
Timeframe: Baseline and 90 days
| Intervention | Days per Month (Mean) |
|---|
| Milnacipran | 3.34 |
| Placebo | 4.62 |
Change in Days Using Headache Medication Per Month From Baseline to 90 Days
"On days where the patient indicated they had a headache (i.e., migraine or non-migraine headache), patients were instructed to complete the diary questions regarding whether they used medication to treat headache pain and related symptoms. This was used to calculate days using headache medication days per month. Days with migraine over a 30 day period were summed to generate a number for each time frame (baseline and 90 days). For the outcome measure, higher positive numbers indicate higher reduction of days using headache medication per month.~Change in days using headache medication = Score[Baseline] - Score[90 days]" (NCT01393522)
Timeframe: Baseline and 90 days
| Intervention | Days per Month (Mean) |
|---|
| Milnacipran | 1.28 |
| Placebo | 2.17 |
Change in VAS Pain Severity
On headache days, patients were instructed to complete a Visual Analog Scale (VAS) to rate their pain intensity. Their response (the scale was 100 cm long) was measured and assigned a score (0-100) with higher numbers indicating more severity. Scores were averaged over a 30 day period to create the score for a time period (baseline and 90 days). Change in Pain score = Score[Baseline] - Score[90 days]. Higher scores indicate greater pain reduction. (NCT01393522)
Timeframe: Baseline and 90 days
| Intervention | units on a scale (Mean) |
|---|
| Milnacipran | 3.23 |
| Placebo | 5.36 |
Change in Migraine Specific Quality of Life - Restrictive
The Migraine Specific Quality of Life measures the impact Migraine has on the patient's Quality of Life. The Restrictive subscale assesses the extent to which migraine restricts the patient's function. The subscale is measured on a standard scale from 0-100, where higher scores indicate better quality of life. For the outcome assessing change, higher positive scores indicate better outcomes. (NCT01393522)
Timeframe: Baseline and 90 days
| Intervention | units on a scale (Mean) |
|---|
| Milnacipran | 21.01 |
| Placebo | 35.03 |
Change in Migraine Specific Quality of Life - Preventive
The Migraine Specific Quality of Life measures the impact Migraine has on the patient's Quality of Life. The Preventive subscale assesses the extent to which migraine prevents the patient's function. The subscale is measured on a standard scale from 0-100, where higher scores indicate better quality of life. For the outcome assessing change, higher positive scores indicate better outcomes. (NCT01393522)
Timeframe: Baseline and 90 days
| Intervention | units on a scale (Mean) |
|---|
| Milnacipran | 21.61 |
| Placebo | 31.26 |
Change in Migraine Specific Quality of Life - Emotional
The Migraine Specific Quality of Life measures the impact Migraine has on the patient's Quality of Life. The Emotional subscale assesses the extent to which migraine influences the patient's emotional function. The subscale is measured on a standard scale from 0-100, where higher scores indicate better quality of life. For the outcome assessing change, higher positive scores indicate better outcomes. (NCT01393522)
Timeframe: Baseline and 90 days
| Intervention | units on a scale (Mean) |
|---|
| Milnacipran | 29.89 |
| Placebo | 37.99 |
Treatment Efficacy Questionnaire (TEQ)
Treatment Efficacy Questionnaire is a measure of treatment effectiveness. The score ranges from 1 to 48, 1 is minimum score and 48 is the maximum score. The investigators was looking to see if the Milnacipran treatment groups have a higher proportion of subjects with significant improvement in efficacy, judged as a TEQ score of >28, compared to placebo group. (NCT01471379)
Timeframe: Twelve Weeks
| Intervention | percentage of subject with score >28 (Number) |
|---|
| Group A (50mg - 100mg) | 0 |
Subject Self Reported Adequate Relief of Pain
The study sought to determine if the Milnacipran arms had a greater proportion of adequate relief over the placebo group. Subjects were asked to answer 'yes' or 'no' as to whether or not they had adequate relief of pain due to irritable bowel syndrome. (NCT01471379)
Timeframe: Twelve Weeks
| Intervention | percentage of participants (Number) |
|---|
| Group A (50mg - 100mg) | 0 |
Number of Participants With Pain Response
Visual Analog Scale (VAS) scores (range 0-100 mm; 0 = none, 100 = worst pain) were recorded for pain before the beginning of the study, at 6 weeks of treatment and at the end visit i.e. 10 weeks. Ideally, VAS would have been administered at the 12th week; however, subject was terminated at the 10th week visit. A positive pain response (ie pain relief) was defined as >30% decrease in the VAS score between baseline and the final study visit. (NCT01471379)
Timeframe: Twelve Weeks
| Intervention | participants (Number) |
|---|
| Group A (50mg - 100mg) | 0 |
PamSys Actigraph Data
We used a body worn sensor (PAMSys™, Biosensics, LLC, MA)(25-27) embedded in a comfortable t-shirt at the sternal level. Participants wore the PAMSys after the visit for 48 hours. The device provides values related to subjects spontaneous physical activity including percentage of time standing and walking. These variables provide different indexes of participants' level of activity and activity organization, and were reported by subjects with KOA pain as relevant. (NCT01510457)
Timeframe: 48 hours after visit 3
| Intervention | percentage of activity (over 48 hours) (Mean) |
|---|
| percentage of time standing | percentage of time walking |
|---|
| Milnacipran | 17.675 | 11.198 |
,| Sugar Pill | 18.154 | 10.218 |
Pain Visual Analogue Scale
Pain Visual Analogue Scale from 0-100 (0= no pain, and 100= most pain). (NCT01510457)
Timeframe: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
| Intervention | units on a 100mm pain scale (Mean) |
|---|
| VAS now Visit 1 | VAS now Visit 3 |
|---|
| Milnacipran | 44 | 20 |
,| Sugar Pill | 55 | 51 |
Pain Disability Index (PDI)
The PDI is a seven-item, validated instrument that assesses perceived disability in seven key life areas. It provides a total disability score, and is an indirect measure of self efficacy. The Pain Disability Scale is a scale from 0 - 70, where 0 = no Disability and 70 = the most Disability. (NCT01510457)
Timeframe: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
| Intervention | units on a disability scale (Mean) |
|---|
| Pain Disability Index (total)_Visit 1 | Pain Disability Index (total)_Visit 3 |
|---|
| Milnacipran | 28 | 15 |
,| Sugar Pill | 31 | 26 |
Pain Anxiety Symptoms Scale (PASS)
Anxiety scores were collected at least two data points. The Pain Anxiety Symptoms Scale (PASS) is a scale from 0 - 100, where 0 = no anxiety and 100 = the most anxiety. (NCT01510457)
Timeframe: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
| Intervention | units on an anxiety scale (Mean) |
|---|
| PASS-20 (total) Visit 1 | PASS-20 (total) Visit 3 |
|---|
| Milnacipran | 34.5 | 22.0 |
,| Sugar Pill | 39.1 | 31.2 |
Daily Diary Entries With Pain, Fatigue and Functioning Scores Three Times a Day
Averages of daily diary outcomes were taken over the first and last week of the trial (week 1 and week 11) to compare pre and post treatment. diary was filled out 3 times a day and asked subjects to rate pain at rest, pain when walking, and fatigue on a scale 0-10 (0=none, and 10=the worst) (NCT01510457)
Timeframe: electronic diary entries with pain, fatigue and functioning scores were completed three times a day during week 1 and week 11
| Intervention | units on a 0-10 NRS scale (Mean) |
|---|
| Ave Pain at rest reported on Diary over Week 1 | Ave Pain at rest reported on Diary over Week 11 | Ave Pain walking reported on Diary over Week 1 | Ave Pain walking reported on Diary over Week 11 | Ave Fatigue reported on Diary over Week 1 | Ave Fatigue reported on Diary over Week 11 |
|---|
| Milnacipran | 4.1 | 2.0 | 5.2 | 3.1 | 4.3 | 3.4 |
,| Sugar Pill | 5.6 | 3.7 | 6.4 | 4.6 | 4.4 | 2.8 |
Center for Epidemiological Studies Depression Scale CESD-10 (CES-D 10)
The CES-D 10 is a 10-item questionnaire that has been validated for the assessment of depressive symptomatology. The Depression Scale is a scale with a sum score from 0 - 30, where 0 = no Depression and 30 = the most Depression. (NCT01510457)
Timeframe: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
| Intervention | units on the depression scale (Mean) |
|---|
| CES-D-10 (total) Visit 1 | CES-D-10 (total) Visit 3 |
|---|
| Milnacipran | 7 | 6 |
,| Sugar Pill | 6 | 9 |
Beck Depression Inventory (BDI-II)
"Self-report evaluation of depressive symptoms.The secondary outcome measure is change in Beck Depression Inventory. The scale for this inventory is:~0-9: indicates minimal depression 10-18: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression. The higher the score the degree of depression." (NCT01777581)
Timeframe: baseline and 10 weeks
| Intervention | units on a scale (Mean) |
|---|
| Values at baseline | Values at endpoint |
|---|
| Milnacipran | 13.8 | 11.6 |
,| Sugar Pill (Placebo) | 14.3 | 13.3 |
Neuropathic Pain Questionnaire
"Self-report evaluation of nerve pain symptoms. A low total cumulative score means less pain and higher cumulative score is greater pain.~Total cumulative scores range form 0 to 1000 where in 0 is absence of pain and 1000 highest pain." (NCT01777581)
Timeframe: baseline and 10 weeks
| Intervention | units on a scale (Mean) |
|---|
| Values at baseline | Values at endpoint |
|---|
| Milnacipran | 415.1 | 238.3 |
,| Sugar Pill (Placebo) | 601.4 | 511.3 |
Oswestry Low Back Pain Disability Questionnaire
"Self report evaluation of various back pain symptoms. For each of 10 sections participants rate pain on a scale of 0-5 in these categories:~Section 1 - Pain intensity~Section 2 - Personal care~Section 3 - Lifting~Section 4 - Walking~Section 5 - Sitting~Section 6 - Standing~Section 7 - Sleeping~Section 8 - Sex life (if applicable)~Section 9 - Social life~Section 10 - Travelling~The scores are combined form each category into overall score. Scores are converted to percentages as follows:~0% to 20%: minimal disability: The patient can cope with most living activities.~21%-40%: moderate disability: The patient experiences more pain and difficulty with sitting, lifting and standing.~41%-60%: severe disability: Pain remains the main problem-activities of daily living are affected.~61%-80%: crippled: Back pain impinges on all aspects of life.~81%-100%: Patients are either bed-bound or exaggerating their symptoms" (NCT01777581)
Timeframe: baseline and 10 weeks
| Intervention | percent score (Mean) |
|---|
| Values at baseline | Values at endpoint |
|---|
| Milnacipran | 20.1 | 18.1 |
,| Sugar Pill (Placebo) | 22.8 | 22.5 |
State-trait Anxiety Inventory (STAI)
"Self-report evaluation of anxiety symptoms.Assessment of subjective symptoms of current anxiety and chronic anxiety.~There are 20 items for assessing trait anxiety and 20 for state anxiety. State anxiety items include: I am tense; I am worried and I feel calm; I feel secure. Trait anxiety items include: I worry too much over something that really doesn't matter and I am content; I am a steady person. All items are rated on a 4-point scale~Scale~1= almost never 4= almost always~Higher scores indicate greater anxiety. Mean cumulative scores were reported" (NCT01777581)
Timeframe: baseline and 10 weeks
| Intervention | units on a scale (Mean) |
|---|
| Values at baseline | Values at endpoint |
|---|
| Milnacipran | 88.4 | 90.0 |
,| Sugar Pill (Placebo) | 86.5 | 84.0 |
Visual Analogue Scale Score Referring to Radicular Pain (VAS-rad)
The primary outcome is change in pain VAS from baseline through 10 weeks. The effect size was calculated using the VAS scores measured on a scale of 0 to 100 mm with 0 being absence of pain or no pain noted and 100 being worst imaginable pain/as bad as can be. The higher the score the greater the over all pain intensity. Mean cumulative total scores were reported. (NCT01777581)
Timeframe: baseline and 10 weeks
| Intervention | units on a scale (Mean) |
|---|
| Values at baseline | Values at endpoint |
|---|
| Milnacipran | 58.7 | 13.6 |
,| Sugar Pill (Placebo) | 67.7 | 59.7 |
Change in Knee Society Score (KSS).
"KSS measures subjective pain and objective function by joint physical exam. This secondary outcome was the change in Knee Society Score(KSS)from baseline through 12 weeks.~KSS scores measured on a scale of 0 to 100 mm:~0 = absence of pain or no pain noted 100= worst imaginable pain/as bad as can be The higher the score the greater the over all pain intensity." (NCT01780389)
Timeframe: between baseline and endpoint (12 weeks or early termination)
| Intervention | units on a scale (Mean) |
|---|
| Milnacipran Open Label | 1.37 |
Change in Pain Visual Analogue Scale(VAS).
"The primary outcome is change in pain VAS from baseline to 12 weeks (baseline score minus 12 week or endpoint score; positive number reflects reduction in pain score). The effect size was calculated using the VAS scores measured on a scale of 0 to 100 mm:~0= absence of pain or no pain noted 100 = worst imaginable pain/as bad as can be The higher the score the greater the over all pain intensity." (NCT01780389)
Timeframe: baseline and endpoint 12 weeks
| Intervention | units on a scale (Mean) |
|---|
| Milnacipran-Open Label | 44 |
Change in the Beck Depression Inventory (BDI-II)
"The secondary outcome measure is change in Beck Depression Inventory. The scale for this inventory is:~0-9: indicates minimal depression 10-18: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression. The higher the score the degree of depression." (NCT01780389)
Timeframe: Baseline to endpoint (12 weeks or early termination)
| Intervention | units on a scale (Mean) |
|---|
| Milnacipran Open Label | 0.49 |
Change in the Montgomery Asberg Depression Rating Scale
"Staff-rated assessment of depressive symptoms. Scale is as follows:~0 to 6 - normal /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression" (NCT01780389)
Timeframe: Between baseline and endpoint (12 weeks or early termination)
| Intervention | units on a scale (Mean) |
|---|
| Milnacipran Open Label | 0.78 |
Change in Total Score of Multidimensional Fatigue Inventory (MFI-20)
"Measures subjective fatigue.20-item self-report instrument consisting of five scales: General Fatigue, Physical Fatigue, Reduced Activity, Reduced Motivation, and Mental Fatigue.~Each scale contains four items rated on a scale of one to 5 with the scale score of one having the anchor of entirely true and the scale score of 5 having the anchor of no, not true. The five scales were identified through factor analysis and are assumed to measure different aspects of fatigue. Lowest possible total score = 20 (absent fatigue) Highest possible total score = 100 (maximum fatigue) Total mean cumulative scores were reported" (NCT01780389)
Timeframe: Baseline to endpoint (12 weeks or early termination)
| Intervention | units on a scale (Mean) |
|---|
| Milnacipran Open Label | 0.46 |
Change in Total Score of State Trait Anxiety Inventory (STAI)
"Assessment of subjective symptoms of current anxiety and chronic anxiety. There are 20 items for assessing trait anxiety and 20 for state anxiety. State anxiety items include: I am tense; I am worried and I feel calm; I feel secure. Trait anxiety items include: I worry too much over something that really doesn't matter and I am content; I am a steady person. All items are rated on a 4-point scale (e.g., from Almost Never to Almost Always). Higher scores indicate greater anxiety.~Lowest total score is 40 (absent anxiety) Highest total score is 160 (maximum anxiety) Total mean cumulative scores were reported." (NCT01780389)
Timeframe: baseline and endpoint (12 weeks or early termination)
| Intervention | units on a scale (Mean) |
|---|
| Milnacipran Open Label | 0.69 |
Visual Analogue Scale for Pain
Visual Analogue Scale for Pain operationally is a 100 mm line anchored by word descriptors at each end. The patient marks a point on the line that reflects their current pain state. The distance in mm from the left anchor point is the score. Higher scores indicate more pain. (NCT01829243)
Timeframe: Baseline, Week 1, 2,4, and 6 weeks
| Intervention | mm (Mean) |
|---|
| Week 0 | Week 1 | Week 2 | Week 4 | week 6 |
|---|
| Milnacipran | 59.4 | 58.5 | 55.7 | 56.9 | 54.4 |
,| Placebo | 68.6 | 66.2 | 61.5 | 54.4 | 60.4 |
MATRICS Consensus Cognitive Battery Composite Score
"(MATRICS) Consensus Cognitive Battery measures cognitive functioning within 7 domains: speed of processing, attention/vigilance, working memory (non verbal and verbal), verbal learning, visual learning, reasoning and problem solving and social cognition.~The composite score is calculated by the MATRICS computer program, which equally weights each of the 7 domain scores. The range of composite scores is 20-80. Higher scores indicate higher levels or cognitive functioning, while lower scores indicate lower levels of cognitive functioning." (NCT01829243)
Timeframe: Baseline, Week 6
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Week 1 |
|---|
| Milnacipran | 41.4 | 41.0 |
,| Placebo | 37.8 | 40.6 |
Changes in The Fatigue Severity Scale (FSS)
"The Fatigue Severity Scale (FSS) is composed of nine items with a seven-point response format. The minimum score = 9 and maximum score possible = 63. Higher scores = greater fatigue severity.~Sample questions include I am easily fatigued and Exercise brings on my fatigue. In the initial validation study, internal consistency for the Fatigue Severity Scale was high for specific illness groups (MS and lupus) and healthy controls. The scale clearly distinguished patients from controls and it was moderately correlated with a single-item visual analogue scale of fatigue intensity. In all patients, clinical improvement in fatigue was associated with reductions in scores on the Fatigue Severity Scale. The Fatigue Severity Scale is also a practical measure due to its brevity and ease of administration and scoring." (NCT01829243)
Timeframe: Baseline, Week 1, 2,4, and 6 weeks
| Intervention | units on a scale (Mean) |
|---|
| Week 0 | Week 1 | Week 2 | Week 4 | Week 6 |
|---|
| Milnacipran | 56.3 | 54.0 | 53.7 | 54.1 | 52.1 |
,| Placebo | 49.2 | 53.4 | 52.2 | 52.8 | 53.0 |
Composite Brief Assessment of Cognition (BAC) Score
The composite BAC score is calculated by scoring each of the 6 individual tests (Verbal Memory Recall, Digit Sequencing, Token Motor Task, Verbal Fluency, Symbol Coding, and Tower of London), comparing each score to a healthy control sample to create z-scores, summing the z-scores, and rescaling the sum. The composite score range is -2127.8 to 1878.8, with higher scores indicating better cognition. (NCT01829243)
Timeframe: Baseline, Week 6
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Week 6 |
|---|
| Milnacipran | 41.2 | 42.9 |
,| Placebo | 40.9 | 42.9 |
Percent of Days of Confirmed Abstinence (Out of 5 Maximum)
Subjects will be asked to abstain for five consecutive days during the third week of each intervention period with the percentage of confirmed abstinence days being the primary outcome measure (NCT02265367)
Timeframe: 5 days
| Intervention | percentage of days non-smoking (Mean) |
|---|
| Levomilnacipran | 46.9 |
| Placebo | 42.0 |
Time to First Relapse During the Double-Blind Treatment Period (DBTP)
Time to relapse for the median was measured in days from randomization date at the start of the DBTP to relapse date during DBTP. Relapse was defined as meeting any 1 or more of the following criteria: 1) Insufficient therapeutic response at any one visit, including a >/= 2 increase in Clinical Global Impressions-Severity (CGI-S) score (range 1 to 7) compared with that obtained at randomization, or risk of suicide as determined by the investigator, or need for hospitalization due to worsening of depression as determined by the investigator, or need for alternative treatment of depressive symptoms as determined by the Investigator; 2) Montgomery-Asberg Depression Rating Scale (MADRS) total score >/= 18 (range 0 to 60) at 2 consecutive visits (second visit within 7 to 14 days after the first visit at which the MADRS total score was ≥ 18). Participant was considered censored at the last visit during DBTP if participant did not meet the relapse criteria during DBTP. (NCT02288325)
Timeframe: From the randomization date (Week 20) to the relapse date during the 26-week DBTP (up to Week 46)
| Intervention | days (Median) |
|---|
| Double-Blind Placebo | NA |
| Double-Blind FETZIMA® | NA |
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scale
The CGI-S is a clinician-rated scale used to rate the severity of the participants current state of mental illness compared with MDD population. The participant was rated on a scale from 1 to 7, where 1= Very much improved; 2= Much improved; 3= Minimally improved; 4= No change; 5= Minimally worse; 6= Much worse; 7= Very much worse. Higher score indicates worsening of mental illness. A negative change from Baseline indicates improvement. MMRM was used for analysis. (NCT02431806)
Timeframe: Baseline (Week 0) to Week 8
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Placebo | -1.54 |
| Levomilnacipran 40 mg/Day | -1.52 |
| Levomilnacipran 80 mg/Day | -1.52 |
| Fluoxetine 20 mg/Day | -1.68 |
Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score
CDRS-R is a 17-item scale measuring presence and severity of symptoms commonly associated with childhood depression and is scored on a 1-to-5- or 1-to-7-point scale. Rating of 1 indicates normal function. The CDRS-R total score ranges from 17 to 113; higher score indicates more severe depression. A negative change from Baseline indicates improvement. Mixed Model for Repeated Measures (MMRM) was used for analysis. (NCT02431806)
Timeframe: Baseline (Week 0) to Week 8
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Placebo | -22.90 |
| Levomilnacipran 40 mg/Day | -23.28 |
| Levomilnacipran 80 mg/Day | -22.64 |
| Fluoxetine 20 mg/Day | -24.37 |
Hamilton Depression Rating Scale (HDRS) Scores 24
This measure includes 24 items. Response options vary item to item and include the following ranges: [0-2], [0-3], and [0-4]. A score of 0 suggests absence of symptoms and/or difficulties and higher scores represent more severe difficulties. Possible overall score range [0-74], higher scores representing more severe difficulties. (NCT02466958)
Timeframe: Baseline and 12 weeks
| Intervention | units on a scale (Mean) |
|---|
| Baseline | 12 Weeks |
|---|
| Levomilnacipran (FETZIMA) | 17.88 | 6.86 |
,| Placebo | 19.92 | 10.33 |
Geriatric Depression (GDS) Scores
The GDS has a total of 30 items with response options [Yes/No]. Total score range is [0-30]. Higher scores represent more severe difficulties. (NCT02466958)
Timeframe: Baseline and 12 weeks
| Intervention | units on a scale (Mean) |
|---|
| Baseline | 12 Weeks |
|---|
| Levomilnacipran (FETZIMA) | 13.5 | 11.71 |
,| Placebo | 15.33 | 11.33 |
Clinical Global Impression Scale (CGI) Scores
7-Point Likert Scale [1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse]. (NCT02466958)
Timeframe: Week 12 reported
| Intervention | units on a scale (Mean) |
|---|
| Levomilnacipran (FETZIMA) | 3.00 |
| Placebo | 3.33 |
Changes of Anxiety Symptoms in Scores on Hamilton Anxiety Rating Scale (HAM-A)
A questionnaire used by clinicians to rate the severity of a patient's anxiety. Total score range of 0-48. A higher score indicates greater anxiety. (NCT02720198)
Timeframe: Baseline to Week 8
| Intervention | score on a scale (Mean) |
|---|
| Levomilnacipran | -3.89 |
| Quetiapine | -5.53 |
Changes in Sexual Dysfunction by Changes in Scores on Arizona Sexual Experience Scale (ASEX)
ASEX is scale for sexual dysfunction to assess safety and tolerability of medication. Total scores range from 5-30. Higher scores indicate greater sexual dysfunction. (NCT02720198)
Timeframe: Baseline to Week 8
| Intervention | score on a scale (Mean) |
|---|
| Levomilnacipran | -0.76 |
| Quetiapine | -0.30 |
Changes in Scores on Apathy Evaluation Scale (AES).
Self-Administered assessment measuring lack of motivation not attributable to diminished level of consciousness, cognitive impairment, or emotional distress. Total scores range from 0-54. Higher scores indicate greater apathy. (NCT02720198)
Timeframe: Baseline to Week 8
| Intervention | score on a scale (Mean) |
|---|
| Levomilnacipran | -2.07 |
| Quetiapine | -1.83 |
Changes in Neurocognition by Changes in Scores on Scores on Digit Symbol Substitution Test (DSST)
DSST measures working memory and visuospatial processing. 1 point for each object correctly substituted from number to each matched symbol. Total score range of 0-89. Higher scores mean better cognitive function. (NCT02720198)
Timeframe: Baseline to Week 8
| Intervention | score on a scale (Mean) |
|---|
| Levomilnacipran | 3.21 |
| Quetiapine | 0.87 |
Changes in Neurocognition by Changes in Scores on Reyes Verbal Learning Test
Number of words correctly recalled by the respondent is recorded. 1 point for each word correctly recalled. Total score range of 0-40. Higher scores mean better cognitive function. (NCT02720198)
Timeframe: Baseline to Week 8
| Intervention | score on a scale (Mean) |
|---|
| Levomilnacipran | 2.28 |
| Quetiapine | 2.90 |
Number of Subjects With Global Improvement in Scores on Clinical Global Impression Scale- Severity (CGI-S)
CGI-S is a 7 point scale that assess the severity of illness and requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. It is used to assess the clinician's view of the patient's global functioning. Total score range of 0-7. (NCT02720198)
Timeframe: Baseline to Week 8
| Intervention | Participants (Count of Participants) |
|---|
| Levomilnacipran | 13 |
| Quetiapine | 13 |
Remission Rate
Remission was defined as [>or=50% reduction in MADRS score with MADRS NCT02720198)
Timeframe: Week 8
| Intervention | Participants (Count of Participants) |
|---|
| Levomilnacipran | 2 |
| Quetiapine | 3 |
Response Rate
Remission was defined as [>or=50% reduction in MADRS score with MADRS or=50% reduction in MADRS with MADRS >10]. Response rate included remission and response. (NCT02720198)
Timeframe: Week 8
| Intervention | Participants (Count of Participants) |
|---|
| Levomilnacipran | 3 |
| Quetiapine | 7 |
Changes of Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
A ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Total scores will range from 0 to 60. Higher scores indicate greater severity of depressive episodes. (NCT02720198)
Timeframe: Baseline to Week 8
| Intervention | score on a scale (Mean) |
|---|
| Levomilnacipran | -5.81 |
| Quetiapine | -6.97 |
Changes of Quality of Life in Scores on Sheehan Disability Scale (SDS) Total
A self-reported brief scale to assess impairment of work/school, social life and family and home. Total score range of 0-30. A higher score indicates greater impairment. (NCT02720198)
Timeframe: Baseline to Week 8
| Intervention | score on a scale (Mean) |
|---|
| Levomilnacipran | -3.79 |
| Quetiapine | -0.10 |
Number of Subjects With General Improvement in Scores on Clinical Global Impression Scale- Improvement (CGI-I)
CGI-I a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. It is used to assess the clinician's view of the patient's global functioning. Total score range of 0-7. (NCT02720198)
Timeframe: Baseline to Week 8
| Intervention | Participants (Count of Participants) |
|---|
| Levomilnacipran | 21 |
| Quetiapine | 24 |
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scale
The CGI-S is a clinician-rated scale used to rate the severity of the participant's current state of mental illness compared with MDD population. The participant was rated on a scale from 1 to 7, where 1=normal, not at all ill and 7=among the most extremely ill participants. Higher score indicates worsening of mental illness. A negative change from Baseline indicates improvement. MMRM was used for analysis. (NCT03569475)
Timeframe: Baseline (Week 0) to Week 8
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Placebo | -1.5 |
| Levomilnacipran ER 40-80 mg/Day | -1.6 |
| Fluoxetine 20 mg/Day | -1.7 |
Change From Baseline in Children's Depression Rating Scale- Revised (CDRS-R)
The CDRS-R is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6-17 years. It contains 17 ordinally-scaled items that evaluate the presence and severity of symptoms commonly associated with childhood depression and is scored on a 1-to-5- or 1-to-7-point scale. Rating of 1 indicates normal function. The CDRS-R total score ranges from 17 to 113; higher score indicates more severe depression. A negative change from Baseline indicates improvement. Mixed Model for Repeated Measures (MMRM) was used for analysis. (NCT03569475)
Timeframe: Baseline (Week 0) to Week 8
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Placebo | -21.3 |
| Levomilnacipran ER 40-80 mg/Day | -23.0 |
| Fluoxetine 20 mg/Day | -23.1 |