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Daniel J Clauw - One of the best experts on this subject based on the ideXlab platform.
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continuing efficacy of Milnacipran following long term treatment in fibromyalgia a randomized trial
Arthritis Research & Therapy, 2013Co-Authors: Daniel J Clauw, Philip J Mease, Robert H Palmer, Joel M Trugman, Yong WangAbstract:Previous studies of long-term treatment response in fibromyalgia and other chronic pain states have generally been limited to approximately one year, leaving questions about the longer-term durability of response. The purpose of this study was to demonstrate continuing efficacy of Milnacipran by characterizing changes in pain and other fibromyalgia symptoms after discontinuing long-term treatment. The mean length of Milnacipran treatment at the time of randomized withdrawal was 36.1 months from initial exposure to Milnacipran (range, 17.9 to 54.4 months). After completing a long-term, open-label, lead-in study of Milnacipran (which followed varying periods of exposure in previous studies), adult patients with fibromyalgia entered the four-week open-label period of the current study for evaluation of ongoing treatment response. After the four-week period to confirm new baseline status, 151 patients taking Milnacipran ≥100 mg/day and reporting ≥50% improvement from pre-Milnacipran exposure in Visual Analogue Scale (VAS) pain scores were classified as responders. These responders entered the 12-week, double-blind withdrawal period in which they were randomized 2:1 to continue Milnacipran or switched to placebo. The prespecified primary parameter was loss of therapeutic response (LTR), defined as increase in VAS pain score to <30% reduction from pre-Milnacipran exposure or worsening of fibromyalgia requiring alternative treatment. Adverse events and vital signs were also monitored. Time to LTR was shorter in patients randomized to placebo than in patients continuing Milnacipran (P < 0.001). Median time to LTR was 56 days with placebo and was not calculable for Milnacipran, because less than half of the latter group of patients lost therapeutic response by study end. Additionally, 81% of patients continuing on Milnacipran maintained clinically meaningful pain response (≥30% improvement from pre-Milnacipran exposure), compared with 58% of patients switched to placebo (sensitivity analysis II; P < 0.001). The incidences of treatment-emergent adverse events were 58% and 47% for placebo and Milnacipran, respectively. Mean decreases in blood pressure and heart rate were found in both groups, with greater decreases for patients switched to placebo. Continuing efficacy of Milnacipran was demonstrated by the loss of effect following withdrawal of treatment in patients who received an average of three years of Milnacipran treatment. ClinicalTrials.gov: NCT01014585
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Continuing efficacy of Milnacipran following long-term treatment in fibromyalgia: a randomized trial
Arthritis research & therapy, 2013Co-Authors: Daniel J Clauw, Philip J Mease, Robert H Palmer, Joel M Trugman, Yong WangAbstract:Previous studies of long-term treatment response in fibromyalgia and other chronic pain states have generally been limited to approximately one year, leaving questions about the longer-term durability of response. The purpose of this study was to demonstrate continuing efficacy of Milnacipran by characterizing changes in pain and other fibromyalgia symptoms after discontinuing long-term treatment. The mean length of Milnacipran treatment at the time of randomized withdrawal was 36.1 months from initial exposure to Milnacipran (range, 17.9 to 54.4 months). After completing a long-term, open-label, lead-in study of Milnacipran (which followed varying periods of exposure in previous studies), adult patients with fibromyalgia entered the four-week open-label period of the current study for evaluation of ongoing treatment response. After the four-week period to confirm new baseline status, 151 patients taking Milnacipran ≥100 mg/day and reporting ≥50% improvement from pre-Milnacipran exposure in Visual Analogue Scale (VAS) pain scores were classified as responders. These responders entered the 12-week, double-blind withdrawal period in which they were randomized 2:1 to continue Milnacipran or switched to placebo. The prespecified primary parameter was loss of therapeutic response (LTR), defined as increase in VAS pain score to
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a pooled analysis of two randomized double blind placebo controlled trials of Milnacipran monotherapy in the treatment of fibromyalgia
Pain Practice, 2011Co-Authors: Michael E Geisser, Yong Wang, Robert H Palmer, Michael R Gendreau, Daniel J ClauwAbstract:Milnacipran has been shown to significantly improve the pain, global well-being, and physical function of fibromyalgia (FM), and is approved by the U.S. Food and Drug Administration for the management of this disorder. Post hoc analyses of data from two pivotal trials were conducted to further assess the clinical benefits of Milnacipran, to determine the impact of baseline pain severity on treatment outcomes, and to confirm the safety and tolerability of this medication in patients with FM. Patients in these trials were randomized to placebo (n=624), Milnacipran 100 mg/day (n=623), or Milnacipran 200 mg/day (n=837). Two different composite responder analyses were used to evaluate efficacy: a 2-measure analysis, requiring ≥30% improvement from baseline visual analog scale 24-hour recall pain scores and a Patient Global Impression of Change (PGIC) score of "very much improved" or "much improved"; and a 3-measure analysis, requiring a ≥6-point improvement from baseline in SF-36 Physical Component Summary scores in addition to the pain and PGIC criteria. Additionally, a pooled analysis of mean changes from baseline pain scores was conducted in order to evaluate the efficacy of Milnacipran over the entire course of treatment. At 3 months, composite responder rates were significantly higher in the Milnacipran treatment groups than in the placebo group (2- and 3-measure composite responder analyses: P ≤ 0.001, both doses vs. placebo). These improvements were not dependent on baseline pain severity. Similar composite responder results were observed in patients who continued treatment for up to 6 months. Significant improvements in mean pain scores were seen with both doses of Milnacipran vs. placebo as early as 1 week after treatment initiation and were sustained for up to 6 months of Milnacipran treatment. The most common adverse events associated with Milnacipran were nausea, headache, and constipation.
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durability of therapeutic response to Milnacipran treatment for fibromyalgia results of a randomized double blind monotherapy 6 month extension study
Pain Medicine, 2010Co-Authors: Don L Goldenberg, Daniel J Clauw, Philip J Mease, Robert H Palmer, Wei Chen, Michael R GendreauAbstract:Objective. To evaluate the durability of improvement and long-term efficacy of Milnacipran treatment in fibromyalgia, to assess efficacy in patients re-randomized from placebo to Milnacipran, and to collect additional information on the tolerability and efficacy of long-term treatment with Milnacipran. Design. A total of 449 patients who successfully completed a 6-month lead-in study enrolled in this 6-month extension study (87.7% of eligible subjects). Patients initially receiving Milnacipran 200 mg/day during the lead-in study were maintained at 200 mg/day (n = 209); patients initially assigned to placebo or Milnacipran 100 mg/day were re-randomized (1:4) to either 100 mg/day (n = 48) or 200 mg/day (n = 192) of Milnacipran for an additional 6 months of treatment. Efficacy assessments included visual analog scale pain ratings, Fibromyalgia Impact Questionnaire (FIQ) total score, and Patient Global Impression of Change (PGIC). Results. Patients continuing on Milnacipran demonstrated a sustained reduction in pain over the full 12-month period. Additional beneficial effects were also maintained, as indicated by the PGIC and FIQ. Patients initially assigned to either placebo or Milnacipran 100 mg/day in the lead-in study and subsequently re-randomized to Milnacipran 200 mg/day in the extension study experienced further improvements in their mean pain scores, FIQ total scores, and PGIC ratings at 1 year. Milnacipran treatment was generally well tolerated. The most commonly reported newly emergent adverse event was nausea. Conclusions. In addition to confirming that Milnacipran safely and effectively improves the multiple symptoms of fibromyalgia, these data indicate that Milnacipran provides 1-year durable efficacy in this patient population.
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the efficacy and safety of Milnacipran for treatment of fibromyalgia a randomized double blind placebo controlled trial
The Journal of Rheumatology, 2009Co-Authors: Philip J Mease, Srinivas G. Rao, Daniel J Clauw, Wei Chen, Michael R Gendreau, Jay D Kranzler, Robert H PalmerAbstract:Objective. To evaluate the safety and efficacy of Milnacipran, a dual norepinephrine and serotonin reuptake inhibitor, in the treatment of fibromyalgia (FM). Methods. A 27-week, randomized, double-blind, multicenter study compared Milnacipran 100 and 200 mg/day with placebo in the treatment of 888 patients with FM. Two composite responder definitions were used to classify each patient’s individual response to therapy. “FM responders” concurrently satisfied response criteria for improvements in pain (visual analog scale 24-h morning recall), patient global impression of change (PGIC), and physical functioning (SF-36 Physical Component Summary); while “FM pain responders” concurrently satisfied response criteria for improvements in pain and PGIC. Results. At the primary endpoint, after 3-month stable dose treatment, a significantly higher percentage of Milnacipran-treated patients met criteria as FM responders versus placebo (Milnacipran 200 mg/day, p = 0.017; Milnacipran 100 mg/day, p = 0.028). A significantly higher percentage of patients treated with Milnacipran 200 mg/day also met criteria as FM pain responders versus placebo (p = 0.032). Significant pain reductions were observed after Week 1 with both Milnacipran doses. At 15 weeks, Milnacipran 200 mg/day led to significant improvements over placebo in pain (realtime, daily and weekly recall; all measures, p Conclusion. Milnacipran is safe and effective for the treatment of multiple symptoms of FM.
Robert H Palmer - One of the best experts on this subject based on the ideXlab platform.
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continuing efficacy of Milnacipran following long term treatment in fibromyalgia a randomized trial
Arthritis Research & Therapy, 2013Co-Authors: Daniel J Clauw, Philip J Mease, Robert H Palmer, Joel M Trugman, Yong WangAbstract:Previous studies of long-term treatment response in fibromyalgia and other chronic pain states have generally been limited to approximately one year, leaving questions about the longer-term durability of response. The purpose of this study was to demonstrate continuing efficacy of Milnacipran by characterizing changes in pain and other fibromyalgia symptoms after discontinuing long-term treatment. The mean length of Milnacipran treatment at the time of randomized withdrawal was 36.1 months from initial exposure to Milnacipran (range, 17.9 to 54.4 months). After completing a long-term, open-label, lead-in study of Milnacipran (which followed varying periods of exposure in previous studies), adult patients with fibromyalgia entered the four-week open-label period of the current study for evaluation of ongoing treatment response. After the four-week period to confirm new baseline status, 151 patients taking Milnacipran ≥100 mg/day and reporting ≥50% improvement from pre-Milnacipran exposure in Visual Analogue Scale (VAS) pain scores were classified as responders. These responders entered the 12-week, double-blind withdrawal period in which they were randomized 2:1 to continue Milnacipran or switched to placebo. The prespecified primary parameter was loss of therapeutic response (LTR), defined as increase in VAS pain score to <30% reduction from pre-Milnacipran exposure or worsening of fibromyalgia requiring alternative treatment. Adverse events and vital signs were also monitored. Time to LTR was shorter in patients randomized to placebo than in patients continuing Milnacipran (P < 0.001). Median time to LTR was 56 days with placebo and was not calculable for Milnacipran, because less than half of the latter group of patients lost therapeutic response by study end. Additionally, 81% of patients continuing on Milnacipran maintained clinically meaningful pain response (≥30% improvement from pre-Milnacipran exposure), compared with 58% of patients switched to placebo (sensitivity analysis II; P < 0.001). The incidences of treatment-emergent adverse events were 58% and 47% for placebo and Milnacipran, respectively. Mean decreases in blood pressure and heart rate were found in both groups, with greater decreases for patients switched to placebo. Continuing efficacy of Milnacipran was demonstrated by the loss of effect following withdrawal of treatment in patients who received an average of three years of Milnacipran treatment. ClinicalTrials.gov: NCT01014585
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Continuing efficacy of Milnacipran following long-term treatment in fibromyalgia: a randomized trial
Arthritis research & therapy, 2013Co-Authors: Daniel J Clauw, Philip J Mease, Robert H Palmer, Joel M Trugman, Yong WangAbstract:Previous studies of long-term treatment response in fibromyalgia and other chronic pain states have generally been limited to approximately one year, leaving questions about the longer-term durability of response. The purpose of this study was to demonstrate continuing efficacy of Milnacipran by characterizing changes in pain and other fibromyalgia symptoms after discontinuing long-term treatment. The mean length of Milnacipran treatment at the time of randomized withdrawal was 36.1 months from initial exposure to Milnacipran (range, 17.9 to 54.4 months). After completing a long-term, open-label, lead-in study of Milnacipran (which followed varying periods of exposure in previous studies), adult patients with fibromyalgia entered the four-week open-label period of the current study for evaluation of ongoing treatment response. After the four-week period to confirm new baseline status, 151 patients taking Milnacipran ≥100 mg/day and reporting ≥50% improvement from pre-Milnacipran exposure in Visual Analogue Scale (VAS) pain scores were classified as responders. These responders entered the 12-week, double-blind withdrawal period in which they were randomized 2:1 to continue Milnacipran or switched to placebo. The prespecified primary parameter was loss of therapeutic response (LTR), defined as increase in VAS pain score to
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a pooled analysis of two randomized double blind placebo controlled trials of Milnacipran monotherapy in the treatment of fibromyalgia
Pain Practice, 2011Co-Authors: Michael E Geisser, Yong Wang, Robert H Palmer, Michael R Gendreau, Daniel J ClauwAbstract:Milnacipran has been shown to significantly improve the pain, global well-being, and physical function of fibromyalgia (FM), and is approved by the U.S. Food and Drug Administration for the management of this disorder. Post hoc analyses of data from two pivotal trials were conducted to further assess the clinical benefits of Milnacipran, to determine the impact of baseline pain severity on treatment outcomes, and to confirm the safety and tolerability of this medication in patients with FM. Patients in these trials were randomized to placebo (n=624), Milnacipran 100 mg/day (n=623), or Milnacipran 200 mg/day (n=837). Two different composite responder analyses were used to evaluate efficacy: a 2-measure analysis, requiring ≥30% improvement from baseline visual analog scale 24-hour recall pain scores and a Patient Global Impression of Change (PGIC) score of "very much improved" or "much improved"; and a 3-measure analysis, requiring a ≥6-point improvement from baseline in SF-36 Physical Component Summary scores in addition to the pain and PGIC criteria. Additionally, a pooled analysis of mean changes from baseline pain scores was conducted in order to evaluate the efficacy of Milnacipran over the entire course of treatment. At 3 months, composite responder rates were significantly higher in the Milnacipran treatment groups than in the placebo group (2- and 3-measure composite responder analyses: P ≤ 0.001, both doses vs. placebo). These improvements were not dependent on baseline pain severity. Similar composite responder results were observed in patients who continued treatment for up to 6 months. Significant improvements in mean pain scores were seen with both doses of Milnacipran vs. placebo as early as 1 week after treatment initiation and were sustained for up to 6 months of Milnacipran treatment. The most common adverse events associated with Milnacipran were nausea, headache, and constipation.
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durability of therapeutic response to Milnacipran treatment for fibromyalgia results of a randomized double blind monotherapy 6 month extension study
Pain Medicine, 2010Co-Authors: Don L Goldenberg, Daniel J Clauw, Philip J Mease, Robert H Palmer, Wei Chen, Michael R GendreauAbstract:Objective. To evaluate the durability of improvement and long-term efficacy of Milnacipran treatment in fibromyalgia, to assess efficacy in patients re-randomized from placebo to Milnacipran, and to collect additional information on the tolerability and efficacy of long-term treatment with Milnacipran. Design. A total of 449 patients who successfully completed a 6-month lead-in study enrolled in this 6-month extension study (87.7% of eligible subjects). Patients initially receiving Milnacipran 200 mg/day during the lead-in study were maintained at 200 mg/day (n = 209); patients initially assigned to placebo or Milnacipran 100 mg/day were re-randomized (1:4) to either 100 mg/day (n = 48) or 200 mg/day (n = 192) of Milnacipran for an additional 6 months of treatment. Efficacy assessments included visual analog scale pain ratings, Fibromyalgia Impact Questionnaire (FIQ) total score, and Patient Global Impression of Change (PGIC). Results. Patients continuing on Milnacipran demonstrated a sustained reduction in pain over the full 12-month period. Additional beneficial effects were also maintained, as indicated by the PGIC and FIQ. Patients initially assigned to either placebo or Milnacipran 100 mg/day in the lead-in study and subsequently re-randomized to Milnacipran 200 mg/day in the extension study experienced further improvements in their mean pain scores, FIQ total scores, and PGIC ratings at 1 year. Milnacipran treatment was generally well tolerated. The most commonly reported newly emergent adverse event was nausea. Conclusions. In addition to confirming that Milnacipran safely and effectively improves the multiple symptoms of fibromyalgia, these data indicate that Milnacipran provides 1-year durable efficacy in this patient population.
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the efficacy and safety of Milnacipran for treatment of fibromyalgia a randomized double blind placebo controlled trial
The Journal of Rheumatology, 2009Co-Authors: Philip J Mease, Srinivas G. Rao, Daniel J Clauw, Wei Chen, Michael R Gendreau, Jay D Kranzler, Robert H PalmerAbstract:Objective. To evaluate the safety and efficacy of Milnacipran, a dual norepinephrine and serotonin reuptake inhibitor, in the treatment of fibromyalgia (FM). Methods. A 27-week, randomized, double-blind, multicenter study compared Milnacipran 100 and 200 mg/day with placebo in the treatment of 888 patients with FM. Two composite responder definitions were used to classify each patient’s individual response to therapy. “FM responders” concurrently satisfied response criteria for improvements in pain (visual analog scale 24-h morning recall), patient global impression of change (PGIC), and physical functioning (SF-36 Physical Component Summary); while “FM pain responders” concurrently satisfied response criteria for improvements in pain and PGIC. Results. At the primary endpoint, after 3-month stable dose treatment, a significantly higher percentage of Milnacipran-treated patients met criteria as FM responders versus placebo (Milnacipran 200 mg/day, p = 0.017; Milnacipran 100 mg/day, p = 0.028). A significantly higher percentage of patients treated with Milnacipran 200 mg/day also met criteria as FM pain responders versus placebo (p = 0.032). Significant pain reductions were observed after Week 1 with both Milnacipran doses. At 15 weeks, Milnacipran 200 mg/day led to significant improvements over placebo in pain (realtime, daily and weekly recall; all measures, p Conclusion. Milnacipran is safe and effective for the treatment of multiple symptoms of FM.
Yong Wang - One of the best experts on this subject based on the ideXlab platform.
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continuing efficacy of Milnacipran following long term treatment in fibromyalgia a randomized trial
Arthritis Research & Therapy, 2013Co-Authors: Daniel J Clauw, Philip J Mease, Robert H Palmer, Joel M Trugman, Yong WangAbstract:Previous studies of long-term treatment response in fibromyalgia and other chronic pain states have generally been limited to approximately one year, leaving questions about the longer-term durability of response. The purpose of this study was to demonstrate continuing efficacy of Milnacipran by characterizing changes in pain and other fibromyalgia symptoms after discontinuing long-term treatment. The mean length of Milnacipran treatment at the time of randomized withdrawal was 36.1 months from initial exposure to Milnacipran (range, 17.9 to 54.4 months). After completing a long-term, open-label, lead-in study of Milnacipran (which followed varying periods of exposure in previous studies), adult patients with fibromyalgia entered the four-week open-label period of the current study for evaluation of ongoing treatment response. After the four-week period to confirm new baseline status, 151 patients taking Milnacipran ≥100 mg/day and reporting ≥50% improvement from pre-Milnacipran exposure in Visual Analogue Scale (VAS) pain scores were classified as responders. These responders entered the 12-week, double-blind withdrawal period in which they were randomized 2:1 to continue Milnacipran or switched to placebo. The prespecified primary parameter was loss of therapeutic response (LTR), defined as increase in VAS pain score to <30% reduction from pre-Milnacipran exposure or worsening of fibromyalgia requiring alternative treatment. Adverse events and vital signs were also monitored. Time to LTR was shorter in patients randomized to placebo than in patients continuing Milnacipran (P < 0.001). Median time to LTR was 56 days with placebo and was not calculable for Milnacipran, because less than half of the latter group of patients lost therapeutic response by study end. Additionally, 81% of patients continuing on Milnacipran maintained clinically meaningful pain response (≥30% improvement from pre-Milnacipran exposure), compared with 58% of patients switched to placebo (sensitivity analysis II; P < 0.001). The incidences of treatment-emergent adverse events were 58% and 47% for placebo and Milnacipran, respectively. Mean decreases in blood pressure and heart rate were found in both groups, with greater decreases for patients switched to placebo. Continuing efficacy of Milnacipran was demonstrated by the loss of effect following withdrawal of treatment in patients who received an average of three years of Milnacipran treatment. ClinicalTrials.gov: NCT01014585
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Continuing efficacy of Milnacipran following long-term treatment in fibromyalgia: a randomized trial
Arthritis research & therapy, 2013Co-Authors: Daniel J Clauw, Philip J Mease, Robert H Palmer, Joel M Trugman, Yong WangAbstract:Previous studies of long-term treatment response in fibromyalgia and other chronic pain states have generally been limited to approximately one year, leaving questions about the longer-term durability of response. The purpose of this study was to demonstrate continuing efficacy of Milnacipran by characterizing changes in pain and other fibromyalgia symptoms after discontinuing long-term treatment. The mean length of Milnacipran treatment at the time of randomized withdrawal was 36.1 months from initial exposure to Milnacipran (range, 17.9 to 54.4 months). After completing a long-term, open-label, lead-in study of Milnacipran (which followed varying periods of exposure in previous studies), adult patients with fibromyalgia entered the four-week open-label period of the current study for evaluation of ongoing treatment response. After the four-week period to confirm new baseline status, 151 patients taking Milnacipran ≥100 mg/day and reporting ≥50% improvement from pre-Milnacipran exposure in Visual Analogue Scale (VAS) pain scores were classified as responders. These responders entered the 12-week, double-blind withdrawal period in which they were randomized 2:1 to continue Milnacipran or switched to placebo. The prespecified primary parameter was loss of therapeutic response (LTR), defined as increase in VAS pain score to
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a pooled analysis of two randomized double blind placebo controlled trials of Milnacipran monotherapy in the treatment of fibromyalgia
Pain Practice, 2011Co-Authors: Michael E Geisser, Yong Wang, Robert H Palmer, Michael R Gendreau, Daniel J ClauwAbstract:Milnacipran has been shown to significantly improve the pain, global well-being, and physical function of fibromyalgia (FM), and is approved by the U.S. Food and Drug Administration for the management of this disorder. Post hoc analyses of data from two pivotal trials were conducted to further assess the clinical benefits of Milnacipran, to determine the impact of baseline pain severity on treatment outcomes, and to confirm the safety and tolerability of this medication in patients with FM. Patients in these trials were randomized to placebo (n=624), Milnacipran 100 mg/day (n=623), or Milnacipran 200 mg/day (n=837). Two different composite responder analyses were used to evaluate efficacy: a 2-measure analysis, requiring ≥30% improvement from baseline visual analog scale 24-hour recall pain scores and a Patient Global Impression of Change (PGIC) score of "very much improved" or "much improved"; and a 3-measure analysis, requiring a ≥6-point improvement from baseline in SF-36 Physical Component Summary scores in addition to the pain and PGIC criteria. Additionally, a pooled analysis of mean changes from baseline pain scores was conducted in order to evaluate the efficacy of Milnacipran over the entire course of treatment. At 3 months, composite responder rates were significantly higher in the Milnacipran treatment groups than in the placebo group (2- and 3-measure composite responder analyses: P ≤ 0.001, both doses vs. placebo). These improvements were not dependent on baseline pain severity. Similar composite responder results were observed in patients who continued treatment for up to 6 months. Significant improvements in mean pain scores were seen with both doses of Milnacipran vs. placebo as early as 1 week after treatment initiation and were sustained for up to 6 months of Milnacipran treatment. The most common adverse events associated with Milnacipran were nausea, headache, and constipation.
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Milnacipran for the treatment of fibromyalgia in adults a 15 week multicenter randomized double blind placebo controlled multiple dose clinical trial
Clinical Therapeutics, 2008Co-Authors: Daniel J Clauw, Philip J Mease, Robert H Palmer, Michael R Gendreau, Yong WangAbstract:Abstract Background: Preclinical and clinical studies have suggested that Milnacipran, a dual norepinephrine-serotonin reuptake inhibitor, may be efficacious in the treatment of fibromyalgia (FM). Objective: This study was conducted to evaluate the efficacy and tolerability of Milnacipran in treating the multiple domains of FM. Methods: This was a multicenter, double-blind, placebo-controlled trial. Adult patients (age 18–70 years) who met 1990 American College of Rheumatology criteria for FM were randomized to receive Milnacipran 100 mg/d, Milnacipran 200 mg/d, or placebo for 15 weeks. Because this was a pivotal registration trial, the primary end points were chosen to investigate efficacy for 2 potential indications: the treatment of FM and the treatment of FM pain. Thus, the 2 primary efficacy end points were rates of FM composite responders and FM pain composite responders. FM composite responders were defined as patients concurrently experiencing clinically meaningful improvements in the following 3 domain criteria: pain (≥30% improvement, as recorded in an electronic diary); patients' global status (a rating of very much improved or much improved on the Patient Global Impression of Change [PGIC] scale); and physical function (a ≥6-point improvement on the 36-item Short-Form Health Survey [SF-36] Physical Component Summary score). FM pain composite responders were defined as those who met the pain and PGIC criteria. Adverse events reported by patients or observed by investigators were recorded throughout the trial. Results: Of 2270 patients screened, 1196 were randomized to receive Milnacipran 100 mg/d (n = 399), Milnacipran 200 mg/d (n = 396), or placebo (n = 401). The majority of patients were female (96.2%) and white (93.5%). The population had a mean age of 50.2 years, a mean baseline weight of 180.8 pounds, and a mean baseline body mass index of 30.6 kg/m 2 . Compared with placebo, significantly greater proportions of Milnacipran-treated patients were FM composite responders (100 mg/d: P = 0.01; 200 mg/d: P = 0.02) and FM pain composite responders (100 mg/d: P = 0.03; 200 mg/d: P = 0.004). Milnacipran was associated with significant improvements in pain after 1 week of treatment (100 mg/d: P = 0.004; 200 mg/d: P = 0.04), as well as significant improvements in multiple secondary efficacy end points, including global status (PGIC: P P P = 0.02), and fatigue (Multidimensional Fatigue Inventory— 100 mg/d: P = 0.04). The most commonly reported adverse events with Milnacipran were nausea (100 mg/d, 34.3%; 200 mg/d, 37.6%), headache (18.0% and 17.7%, respectively), and constipation (14.3% and 17.9%). Adverse events resulted in premature study discontinuation in 19.5% and 23.7% of those who received Milnacipran 100 and 200 mg/d, respectively, compared with 9.5% of placebo recipients. Conclusion: In these adult patients with FM, both doses of Milnacipran (100 and 200 mg/d) were associated with significant improvements in pain and other symptoms. Clinical Trials Identification Number: NCT00098124.
Fabienne Marcaillou - One of the best experts on this subject based on the ideXlab platform.
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Milnacipran poorly modulates pain in patients suffering from fibromyalgia a randomized double blind controlled study
Drug Design Development and Therapy, 2018Co-Authors: Gisèle Pickering, Nicolas Macian, Noémie Delage, Pascale Picard, Jean-michel Cardot, Fatiha Giron, Christian Dualé, Bruno Pereira, Sophia Sickoutarondo, Fabienne MarcaillouAbstract:Introduction Fibromyalgia is characterized by widespread and chronic pain, and its prevalence is increasing worldwide. Milnacipran, an antidepressant, is often prescribed for fibromyalgia with a possible beneficial effect on central pain modulation. The aim of this study was to evaluate if Milnacipran could modify the status of conditioned pain modulation (CPM) in patients suffering from fibromyalgia. Design and setting Randomized, double-blind controlled trial. Subjects and methods Women with fibromyalgia received Milnacipran 100 mg or placebo. The primary end point was the evolution of CPM with treatments after a 30-second painful stimulus. Secondary outcomes included the predictability of Milnacipran efficacy from CPM performance, evolution of global pain, mechanical sensitivity, thermal pain threshold, mechanical allodynia, cognitive function, and tolerance. Results Fifty-four women with fibromyalgia (46.7±10.6 years) were included and randomized, and 24 patients were analyzed in each group. At inclusion, CPM was dysfunctional (CPM30=-0.5±1.9), and global pain was 6.5±1.8. After treatment, there was a nonsignificant CPM difference between Milnacipran and placebo (CPM30=-0.46±1.22 vs -0.69±1.43, respectively, p=0.55) and 18.8% vs 6.3% (p=0.085) patients did reactivate CPM after Milnacipran vs placebo. Initial CPM was not a predictor of Milnacipran efficacy. Global pain, mechanical and thermal thresholds, allodynia, cognition, and tolerance were not significantly different between both groups. Conclusion Milnacipran did not display a significant analgesic effect after 1-month treatment, but the tendency of Milnacipran to reactivate CPM in a number of patients must be explored with longer treatment duration in future studies and pleads for possible subtypes of fibromyalgia patients.
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Milnacipran poorly modulates pain in patients suffering from fibromyalgia: a randomized double-blind controlled study
Drug Design Development and Therapy, 2018Co-Authors: Gisèle Pickering, Nicolas Macian, Noémie Delage, Pascale Picard, Jean-michel Cardot, Sophia Sickout-arondo, Fatiha Giron, Christian Dualé, Bruno Pereira, Fabienne MarcaillouAbstract:Introduction: Fibromyalgia is characterized by widespread and chronic pain, and its prevalence is increasing worldwide. Milnaeipran, an antidepressant, is often prescribed for fibromyalgia with a possible beneficial effect on central pain modulation. The aim of this study was to evaluate if milnaeipran could modify the status of conditioned pain modulation (CPM) inpatients suffering from fibromyalgia. Design and setting: Randomized, double-blind controlled trial. Subjects and methods: Women with fibromyalgia received milnaeipran 100 mg or placebo. Tlie primary end point was the evolution of CPM with treatments after a 30-second painful stimulus. Secondary outcomes included the predictability of milnaeipran efficacy from CPM performance, evolution of global pain, mechanical sensitivity, thermal pain threshold, mechanical allodynia, cognitive function, and tolerance. Results: Fifty-four women with fibromyalgia (46.7 +/- 10.6 years) were included and randomized, and 24 patients were analyzed in each group. At inclusion. CPM was dysfunctional (CPM30=-0.5 +/- 1.9), and global pain was 6.5 +/- 1.8. After treatment, there was a nonsignificant CPM difference between milnaeipran and placebo (CPM30=-0.46 +/- 1 .22 vs -0.69 +/- 1.43. respectively, p=0.55) and 18.8% vs 6.3 % (p=0.085) patients did reactivate CPM alter Milnacipran vs placebo. Initial CPM was not a predictor of milnaeipran efficacy. Global pain, mechanical and thermal thresholds, allodynia, cognition, and tolerance were not significantly different between both groups. Conclusion: Milnaeipran did not display a significant analgesic effect after 1-month treatment, but the tendency of milnaeipran to reactivate CPM in a number of patients must be explored with longer treatment duration in future studies and pleads for possible subtypes of fibromyalgia patients.
A Tournoux - One of the best experts on this subject based on the ideXlab platform.
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A randomised, double-blind comparison of Milnacipran and imipramine in the treatment of depression
Journal of affective disorders, 2002Co-Authors: A.p Van Amerongen, G Ferrey, A TournouxAbstract:This multicentre, double-blind, randomised trial in 109 patients compared the efficacy and tolerance of the novel selective serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressant Milnacipran (50 mg twice daily, n=53) with the established tricyclic agent imipramine (75 mg twice daily, n=56) over a period of 6 weeks, in patients with major depression (Montgomery-Asberg depression rating score (MADRS) > or =25). Initiation of antidepressant medication was conducted during a 2-week period of hospitalisation, after a 3- to 7-day washout period. Concomitant psychiatric medication was limited to lorazepam, cyamemazine, chloral hydrate and long-term uncomplicated lithium therapy. Assessment for efficacy using the MADRS and Hamilton rating scales of depression, a visual analogue scale and global evaluation revealed both agents to be highly effective (P=0.0001) in this group of patients. Milnacipran was found to be of similar efficacy to imipramine. Tolerance, assessed by physiological and biochemical examinations with routine inventory and spontaneous report of adverse events, revealed a clear advantage for Milnacipran. The incidence of anticholinergic events with Milnacipran was about half that with imipramine and the overall incidence of adverse events by either reporting method was markedly lower with Milnacipran than with imipramine. Furthermore, the patient drop-out rate with imipramine was double that experienced with Milnacipran. Milnacipran appears to possess equal antidepressant efficacy to imipramine but with markedly superior tolerance. Therefore, Milnacipran constitutes an important new treatment option in major depression.
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A double-blind comparison of the efficacy and safety of Milnacipran and fluoxetine in depressed inpatients.
International clinical psychopharmacology, 1998Co-Authors: J. D. Guelfi, A Tournoux, M Ansseau, E Corruble, J C Samuelian, I. Tonelli, Y PletanAbstract:This double-blind, randomised, multicentre study compared the antidepressant efficacy and safety of two doses of Milnacipran (100 mg/day and 200 mg/day) and fluoxetine (20 mg/day) in 289 inpatients with endogenous depression. After a placebo washout period of 4-7 days, assessments were performed weekly during the first 4 weeks, and then after 6, 8 and 12 weeks, using the 17-item Hamilton Depression Rating Scale (HDRS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI). HDRS total score was reduced by a mean of 14.8 in the Milnacipran 100 mg/day group, 12.9 in the Milnacipran 200 mg/day group and 12.1 in the fluoxetine 20 mg/day group. MADRS total score decreased by 17.4, 15.8 and 14.6, respectively. No significant difference could be shown between the three treatment groups for either the HDRS or MADRS total scores. However, the time-by-time change showed a trend in favour of Milnacipran 100 mg/day, which was found significantly superior to fluoxetine at day 28 for several converging parameters (MADRS, CGI-3). Overall, efficacy ratings for all parameters were highest for Milnacipran 100 mg/day, followed by Milnacipran 200 mg/day and fluoxetine 20 mg/day. Side-effect profiles were not significantly different between groups except for a significantly greater frequency of dose-related increase in heart rate > or = 100 bpm in Milnacipran recipients and a significantly greater weight loss in fluoxetine recipients.
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comparative studies with Milnacipran and tricyclic antidepressants in the treatment of patients with major depression a summary of clinical trial results
International Clinical Psychopharmacology, 1996Co-Authors: Siegfried Kasper, A Solles, Y Pletan, A TournouxAbstract:Milnacipran is a novel antidepressant agent which selectively inhibits the reuptake of serotonin and noradrenaline. Seven randomized, double-blind trials with a comparable design have compared the efficacy and tolerability of Milnacipran with that of tricyclic antidepressants (TCAs) in patients with major depression. At a dose of 50 mg twice a day, Milnacipran therapy is associated with a response rate (50% reduction in Hamilton Depression Rating Scale) of 64%. The rate of response to TCAs in these studies was 67%. In contrast to the TCAs, Milnacipran was very well tolerated by the patients. The only adverse event that occurred more frequently in Milnacipran-treated patients than in TCA-treated patients was dysuria (2.1% of patients treated with Milnacipran). Milnacipran is as effective as TCAs in the treatment of patients with major depression and is better tolerated. Milnacipran's lack of effects on cardiovascular function offers improved safety in cases of overdose.
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Milnacipran and selective serotonin reuptake inhibitors in major depression.
International Clinical Psychopharmacology, 1996Co-Authors: J. Lopez-ibor, A Tournoux, Y Pletan, J. D. Guelfi, J F ProstAbstract:In drug development the move from tricyclic antidepressants (TCAs) to selective serotonin reuptake inhibitors (SSRIs) involved not only the loss of the direct receptor interactions responsible for the adverse side effects of TCAs, but also the ability to inhibit the reuptake of noradrenaline. Selectivity for the single neurotransmitter, serotonin, may explain why SSRIs tend to be less efficacious than the TCAs, especially in more serious forms of depression. The advent of selective serotonin and noradrenaline reuptake inhibitors (SNRIs) has tended to confirm the idea that an action on both monoamine systems is important for maximal antidepressant efficacy. This paper reviews clinical trials comparing the new SNRI Milnacipran with the SSRIs fluoxetine and fluvoxamine. A meta-analysis of the principal trials shows greater response rates (the proportion of patients with a decrease in symptom scores of 50% or more) with Milnacipran (50 mg twice a day) than with fluoxetine (20 mg once a day), or fluvoxamine (100 mg twice a day) (Milnacipran : 64% ; SSRIs : 50%). Remission rates (the proportion of patients with Hamilton Depression Rating Scores of 7 or below) were also higher with Milnacipran than with SSRIs (39 versus 28%). In one study, in which 100 mg Milnacipran was given once a day in the evening, the higher response rate obtained with fluoxetine appears to be largely attributable to an inappropriate Milnacipran dosage regimen. Data from a pharmacovigilance database including all patients participating in clinical trials with Milnacipran (n = 5732) showed that, compared with the SSRIs, Milnacipran produced fewer gastrointestinal side effects, such as nausea, and less anxiety. Milnacipran was, however, associated with a higher incidence of headache, dry mouth and dysuria. The results of these studies suggest that Milnacipran is superior in efficacy to SSRIs and is equally well tolerated. Milnacipran, therefore, appears to offer a therapeutic advantage over the SSRIs.
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Clinical efficacy of Milnacipran: placebo-controlled trials.
International Clinical Psychopharmacology, 1996Co-Authors: Yves Lecrubier, A Solles, Y Pletan, A Tournoux, V. MagneAbstract:The clinical efficacy of Milnacipran, a selective serotonin and noradrenaline reuptake inhibitor, was reviewed on the basis of three, multicentre, placebo-controlled trials in major depression. A dose-range study showed the superiority of Milnacipran at 50 or 100 mg twice a day compared with placebo whereas the effect of 25 mg twice a day was not clearly distinguished from that of placebo. This has been confirmed by other studies where the 50-mg twice-a-day regimen was shown to be significantly more efficacious than placebo on all outcome measures (Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale, Clinical Global Impression). The positive results in the individual studies were supported by a meta-analysis of the data from the three studies. A subgroup analysis of hospitalized patients in the meta-analysis showed an advantage for Milnacipran, suggesting that Milnacipran is effective in more severe depression.