Longterm Therapeutic Response to Milnacipran Treatment for Fibromyalgia. A European 1-Year Extension Study Following a 3-Month Study

2011 ◽  
Vol 38 (7) ◽  
pp. 1403-1412 ◽  
Author(s):  
JAIME C. BRANCO ◽  
PATRICK CHERIN ◽  
AGNES MONTAGNE ◽  
ATHMANE BOUROUBI
Keyword(s):  
Fibromyalgia Impact Questionnaire ◽  
Change Score ◽  
Extension Study ◽  
Therapeutic Effects ◽  
Double Blind ◽  
Quality Of Life Measures ◽  
Common Drug ◽  
Patient Global Impression ◽  
Global Impression Of Change

Objective.This double-blind, 1-year extension study investigated the longterm efficacy and safety of milnacipran 100, 150, and 200 mg/day in the treatment of fibromyalgia (FM) in completers of a 3-month European double-blind lead-in study of milnacipran 200 mg/day versus placebo.Methods.A total of 468 patients with FM successfully completing the lead-in study were either blindly maintained on milnacipran 200 mg/day (MLN200:MLN200, n = 198) or (if previously receiving placebo) rerandomized to milnacipran 100 mg/day (PBO:MLN100, n = 91), 150 mg/day (PBO:MLN150, n = 92), or 200 mg/day (PBO:MLN200, n = 87) for an additional 12 months (including a 4-week dose escalation). The main efficacy endpoint was a 2-measure composite responder rate (relative to lead-in study baseline) incorporating the weekly-recall pain score recorded on a visual analog scale and the Patient Global Impression of Change score. A panel of other assessments including the Fibromyalgia Impact Questionnaire explored the multidimensional aspects of FM. Descriptive analyses using the last observation carried forward approach were performed.Results.At the 1-year endpoint, the proportion of composite responders (relative to the lead-in study baseline) ranged from 27.5% (PBO:MLN100) to 35.9% (MLN200:MLN200), and had increased from the extension study baseline by 15.2% (PBO:MLN150) to 20.7% (PBO:MLN200 and MLN200:MLN200). At endpoint, an improvement from both baselines was shown in all groups on pain, fatigue, sleep, and quality of life measures. Up to 1 year, all doses of milnacipran were safe and well tolerated. The most common drug-related adverse events were hyperhidrosis and nausea.Conclusion.Over 1 year, milnacipran 100, 150, and 200 mg/day exhibited sustained and safe therapeutic effects on predominant symptoms of FM. Registered as trial no.NCT00757731.

485 Efficacy and Safety of Once- and Twice-Nightly Dosing of Lower-Sodium Oxybate in Adults With Idiopathic Hypersomnia

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A191-A192
Author(s):  
Isabelle Arnulf ◽  
Anne Marie Morse ◽  
Patricia Chandler ◽  
Rupa Parvataneni ◽  
Dan Chen ◽  
...  
Keyword(s):  
Sodium Oxybate ◽  
Mean Difference ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Patient Global Impression ◽  
Idiopathic Hypersomnia ◽  
Secondary Endpoints ◽  
Global Impression Of Change

Abstract Introduction Idiopathic hypersomnia (IH) is a rare central hypersomnolence disorder. In a randomized, controlled study of lower-sodium oxybate (LXB; Xywav™) in adults with IH (NCT03533114), significant differences for LXB compared with placebo were observed in Epworth Sleepiness Scale (ESS; primary efficacy endpoint), self-reported Patient Global Impression of Change (PGIc), and IH Severity Scale (IHSS; key secondary endpoints). In this clinical study, investigators were permitted to initiate LXB dosing on a once-nightly or twice-nightly regimen. Methods Eligible participants aged 18–75 years began LXB treatment, administered once or twice nightly during an open-label treatment/titration and optimization period (OLTTOP; 10–14 weeks); dose amount/regimen could be adjusted during this period. Participants next entered a 2-week, open-label, stable-dose period (SDP), then were randomized to placebo or to continue LXB treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP). P values are nominal for this exploratory analysis. Results Of 154 enrolled participants, 40 (26%) initiated LXB treatment on a once-nightly regimen. In the efficacy population (n=115), 27 participants were on a once-nightly regimen during SDP (48.1% of whom initiated treatment once nightly during OLTTOP) and 88 participants were on a twice-nightly regimen during SDP (86.4% of whom initiated treatment twice nightly during OLTTOP). During SDP, median (min, max) LXB total dose was 4.5 (2.5, 6) g/night (once-nightly group) and 7.5 (4.5, 9) g/night (twice-nightly group). ESS scores worsened in participants randomized to placebo vs those continuing LXB in the once-nightly group (n=11 and n=15, respectively; LS mean difference [95% CI]: −4.93 [−7.41, −2.46]; P=0.0004) and twice-nightly group (n=47 and n=41, respectively; LS mean difference [95% CI]: −7.44 [−9.15, −5.72]; P<0.0001). Worsening was also observed in PGIc (once-nightly: 81.8% [placebo] vs 26.7% [LXB]; P=0.0077; twice-nightly: 89.4% [placebo] vs 19.5% [LXB]; P<0.0001) and IHSS score (estimated median difference [95% CI], once-nightly: −9.00 [−16.0, −3.0]; P=0.0028; twice-nightly: −12.00 [−15.0, −8.0]; P<0.0001). Common adverse events included nausea (21.4%), headache (16.2%), anxiety (14.9%), dizziness (11.7%), insomnia (11.7%), and vomiting (10.4%). Conclusion The efficacy and safety of LXB in IH were demonstrated for both once-nightly and twice-nightly regimens. The majority of participants initiated and remained on a twice-nightly regimen. Support (if any) Jazz Pharmaceuticals

scholarly journals Psychometric assessment of the PROMIS Fatigue Short Form 6a in women with moderate-to-severe endometriosis-associated pain

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Robin Pokrzywinski ◽  
Ahmed M. Soliman ◽  
Eric Surrey ◽  
Michael C. Snabes ◽  
Karin S. Coyne
Keyword(s):  
Internal Consistency ◽  
Short Form ◽  
Intraclass Correlation ◽  
Change Score ◽  
Reproductive Age ◽  
Phase Iii ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Good Reliability ◽  
Global Impression Of Change

Abstract Background Endometriosis is a common problem in women of reproductive age and has impacts on health-related quality of life and productivity. Fatigue is an important part of the burden of endometriosis, it is not often included as an endpoint in clinical trials. Objectives The study assessed the psychometric properties of the PROMIS Fatigue Short Form 6a in women with moderate-to-severe endometriosis-associated pain. Methods In a phase III double-blind, placebo-controlled clinical trial (NCT01620528), women aged 18–49 years with moderate-to-severe endometriosis-related pain were randomized to elagolix 150 mg once daily, elagolix 200 mg twice daily, or placebo for 6 months. PROMIS Fatigue and dysmenorrhea and non-menstrual pelvic pain (NMPP) scores were assessed at baseline and months 1, 3, and 6, and Patient Global Impression of Change (PGIC) was assessed at months 1, 3, and 6. Reliability (internal consistency and test-retest reliability), construct validity (convergent and known groups validity), and responsiveness were evaluated. Results The analysis included 871 women, mean age 31.5 years. Internal consistency supported a single concept (Cronbach’s alpha 0.93). For the 238 patients with no change in PGIC at month 1, the intraclass correlation coefficient for the PROMIS Fatigue T-score was 0.7 and paired t-test statistically significant (2.84, p = 0.0049). Correlations with other measures were expected to be fairly low as concepts were not redundant. The PROMIS Fatigue discriminated among known groups with mean scores of 55.3, 62.3, and 65.8 at month 3 (PGIC improvement, no change, worsening, respectively). Statically significant discrimination, and change score responsiveness, were seen using clinically relevant anchors (dysmenorrhea and NMPP) at months 3 and 6 between responders and non-responders. Anchor-based (PGIC) responsiveness showed significant improvement from baseline to months 3 and 6 (p < 0.0001). Conclusions PROMIS Fatigue has good reliability, validity, and responsiveness in women with moderate-to-severe endometriosis-associated pain.

Comparative Efficacy and Safety of Sertraline Versus Nortriptyline in Major Depression in Patients 70 and Older

1999 ◽  
Vol 11 (1) ◽  
pp. 85-99 ◽  
Author(s):  
Sanford I. Finkel ◽  
Ellen M. Richter ◽  
Cathryn M. Clary
Keyword(s):  
Major Depression ◽  
Rating Scale ◽  
Antidepressant Treatment ◽  
Change Score ◽  
Attrition Rate ◽  
Double Blind ◽  
Almost All ◽  
Positive Effect ◽  
Population Segment

Background. Few randomized, double-blind studies that examine antidepressant treatment in patients 70 years and older are available. To provide additional data on the safety and efficacy of antidepressants in this rapidly growing population segment, a subgroup analysis of a larger sertraline vs. nortriptyline elderly depression treatment study was performed. Methods. Outpatients (N = 76) who met DSM-III-R criteria for major depression with a minimum Hamilton Depression Rating Scale (HAM-D) severity score of 18 were randomized to 12 weeks of flexible dose treatment with sertraline (50–150 mg) or nortriptyline (25–100 mg). Results. Both treatments significantly improved depression as measured by the HAM-D and Clinical Global Impression scales. At Weeks 10, 12, and endpoint, sertraline demonstrated a significantly greater reduction in depression severity compared to nortriptyline as measured by improvement on the 24-item HAM-D (mean adjusted change score of 14.8 vs. 7.6, respectively, at Week 12; p = .001). Sixty-five percent of sertraline-treated patients were responders by Week 12 (50% or greater reduction from baseline in 24-item HAM-D score) compared to 26% of nortriptyline-treated patients (p < .05). Sertraline treatment had a significantly more positive effect, when compared to nortriptyline, across almost all associated measures of cognitive function, energy, anxiety, and quality of life and was better tolerated than nortriptyline, with a lower attrition rate/side effect burden. Conclusion. The efficacy advantage of sertraline appeared to be even greater in this subgroup of older patients drawn from a larger treatment study of depression that included elderly individuals over the age of 60.

scholarly journals Randomized, Placebo-Controlled, Double-Blind Pilot Study of D-Cycloserine in Chronic Stroke

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Andrew J. Butler ◽  
Justiss Kallos ◽  
Stephen N. Housley ◽  
Michelle C. LaPlaca ◽  
Stephen F. Traynelis ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Stroke Survivors ◽  
Double Blind ◽  
Quality Of Life Measures ◽  
Nmda Receptor Function ◽  
The Usa ◽  
Physical Therapy Treatment ◽  
Preliminary Study ◽  
Therapy Treatment

Stroke is a leading cause of death and disability in the USA. Up to 60% of patients do not fully recover despite intensive physical therapy treatment. N-Methyl-D-aspartate receptors (NMDA-R) have been shown to play a role in synaptic plasticity when activated. D-Cycloserine promotes NMDA receptor function by binding to receptors with unoccupied glycine sites. These receptors are involved in learning and memory. We hypothesized that D-cycloserine, when combined with robotic-assisted physiotherapy (RAP), would result in greater gains compared with placebo + RAP in stroke survivors. Participants (n=14) were randomized to D-cycloserine plus RAP or placebo plus RAP. Functional, cognitive, and quality-of-life measures were used to assess recovery. There was significant improvement in grip strength of the affected hand within both groups from baseline to 3 weeks (95% confidence interval for mean change, 3.95 ± 2.96 to 4.90 ± 3.56 N for D-cycloserine and 5.72 ± 3.98 to 8.44 ± 4.90 N for control). SIS mood domain showed improvement for both groups (95% confidence interval for mean change, 72.6 ± 16.3 to 82.9 ± 10.9 for D-cycloserine and 82.9 ± 13.5 to 90.3 ± 9.9 for control). This preliminary study does not provide evidence that D-cycloserine can provide greater gains in learning compared with placebo for stroke survivors.

The Efficacy and Safety of Milnacipran for Treatment of Fibromyalgia. A Randomized, Double-blind, Placebo-controlled Trial

2009 ◽  
Vol 36 (2) ◽  
pp. 398-409 ◽  
Author(s):  
PHILIP J. MEASE ◽  
DANIEL J. CLAUW ◽  
R. MICHAEL GENDREAU ◽  
SRINIVAS G. RAO ◽  
JAY KRANZLER ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Response To Therapy ◽  
Response Criteria ◽  
Individual Response ◽  
Double Blind ◽  
Patient Global Impression ◽  
Sf 36 ◽  
Pain Visual Analog Scale ◽  
Global Impression Of Change ◽  
Multiple Symptoms

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 < 0.05), PGIC (p < 0.001), fatigue (p = 0.016), cognition (p = 0.025), and multiple SF-36 domains. Milnacipran was safe and well tolerated by the majority of patients during 27 weeks of treatment; nausea and headache were the most common adverse events.Conclusion.Milnacipran is safe and effective for the treatment of multiple symptoms of FM.

scholarly journals Clinical impact of confinement due to the COVID-19 pandemic on patients with fibromyalgia: A cohort study

2020 ◽  
Author(s):  
Javier Rivera ◽  
Isabel Castrejón ◽  
Laura Vallejo-Slocker ◽  
Martin Offenbächer ◽  
Juan Molina-Collada ◽  
...  
Keyword(s):  
Daily Living ◽  
Clinical Manifestations ◽  
Repeated Measurements ◽  
Anxiety And Depression ◽  
Passive Coping ◽  
Patient Global Impression ◽  
Clinical Impairment ◽  
Index Of Severity ◽  
Global Impression Of Change

Abstract Background: Data on the effect of the COVID-19 pandemic on fibromyalgia (FM) patients are lacking. FM patients often experience clinical impairment with stress situations.The objective of this study was to determine whether severity of FM increases because of confinement due to the COVID-19 pandemic.Methods: Prospective study including patients from the Combined Index of Severity of Fibromyalgia (ICAF) cohort who met the 2010 ACR FM criteria. In this cohort, all patients have a periodical evaluation of their quality of life through two questionnaires, the ICAF -which assesses the ability to perform daily living activities, anxiety and depression-, and through the Patient Global Impression of Change (PGIC), which assesses overall change after a therapeutical intervention. Pre and post-confinement measurements were analyzed. Inferential statistical analysis and ANOVA for repeated measurements were used.Results: A total of 93 patients received a phone consultation, (95.5% females), mean (SD) age of 48.23 (8.38) years. Four patients were excluded as presenting COVID-19 and 51 (57%) completed the post-confinement ICAF. Following confinement, 25 (49%) patients got worse (group worse) and 26 (51%) patients experienced no change or improved (group stable). Comparisons between pre and post confinement ICAF did not show significant differences in both groups. Passive coping was significantly different in group worse in pre-confinement evaluation. In the 80% of patients with passive coping predominance there were no change in coping strategy.Conclusions: No clinical impairment due to COVID-19 confinement occurred. The perceived worsening among FM patients relies primarily on how patients cope with their disease, without a real impact on clinical manifestations.

scholarly journals Ingestion of a THC-Rich Cannabis Oil in People with Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Pain Medicine ◽  
2020 ◽  
Vol 21 (10) ◽  
pp. 2212-2218
Author(s):  
Carolina Chaves ◽  
Paulo Cesar T Bittencourt ◽  
Andreia Pelegrini
Keyword(s):  
Quality Of Life ◽  
Clinical Trial ◽  
Placebo Group ◽  
Low Cost ◽  
Fibromyalgia Impact Questionnaire ◽  
Health Condition ◽  
Depression Score ◽  
Controlled Clinical Trial ◽  
Double Blind

Abstract Objective To determine the benefit of a tetrahydrocannabinol (THC)-rich cannabis oil on symptoms and quality of life of fibromyalgia patients. Methods A double-blind, randomized, placebo-controlled clinical trial was conducted for eight weeks to determine the benefit of a THC-rich cannabis oil (24.44 mg/mL of THC and 0.51 mg/mL of cannabidiol [CBD]) on symptoms and quality of life of 17 women with fibromyalgia, residents of a neighborhood with a low socioeconomic profile and a high incidence of violence in the city of Florianopolis, Brazil. The initial dose was one drop (∼1.22 mg of THC and 0.02 mg of CBD) a day with subsequent increases according to symptoms. The Fibromyalgia Impact Questionnaire (FIQ) was applied at pre- and postintervention moments and in five visits over eight weeks. Results There were no significant differences on baseline FIQ score between groups. However, after the intervention, the cannabis group presented a significant decrease in FIQ score in comparison with the placebo group (P = 0.005) and in comparison with cannabis group baseline score. (P &lt; 0.001). Analyzing isolated items on the FIQ, the cannabis group presented significant improvement on the “feel good,” “pain,” “do work,” and “fatigue” scores. The placebo group presented significant improvement on the “depression” score after intervention. There were no intolerable adverse effects. Conclusions Phytocannabinoids can be a low-cost and well-tolerated therapy to reduce symptoms and increase the quality of life of patients with fibromyalgia. Future studies are still needed to assess long-term benefits, and studies with different varieties of cannabinoids associated with a washout period must be done to enhance our knowledge of cannabis action in this health condition.

Minimal Clinically Important Difference in the Fibromyalgia Impact Questionnaire

2009 ◽  
Vol 36 (6) ◽  
pp. 1304-1311 ◽  
Author(s):  
ROBERT M. BENNETT ◽  
ANDREW G. BUSHMAKIN ◽  
JOSEPH C. CAPPELLERI ◽  
GERGANA ZLATEVA ◽  
ALESIA B. SADOSKY
Keyword(s):  
Clinical Utility ◽  
Minimal Clinically Important Difference ◽  
Fibromyalgia Impact Questionnaire ◽  
Pooled Analysis ◽  
Meaningful Change ◽  
Clinically Important Difference ◽  
Patient Global Impression ◽  
Change In The Mean ◽  
The Mean ◽  
Global Impression Of Change

Objective.The Fibromyalgia Impact Questionnaire (FIQ) is a disease-specific composite instrument that measures the effect of problems experienced by patients with fibromyalgia (FM). Utilization of the FIQ in measuring changes due to interventions in FM requires derivation of a clinically meaningful change for that instrument. Analyses were conducted to estimate the minimal clinically important difference (MCID), and to propose FIQ severity categories.Methods.Data from 3 similarly designed, 3-month placebo-controlled, clinical treatment trials of pregabalin 300, 450, and 600 mg/day in patients with FM were modeled to estimate the change in the mean FIQ total and stiffness items corresponding to each category on the Patient Global Impression of Change. FIQ severity categories were modeled and determined using established pain severity cutpoints as an anchor.Results.A total of 2228 patients, mean age 49 years, 93% women, with a mean baseline FIQ total score of 62 were treated in the 3 studies. Estimated MCID on a given measure were similar across the studies. In a pooled analysis the estimated MCID (95% confidence interval) was 14% (13; 15) and for FIQ stiffness it was 13% (12; 14). In the severity analysis a FIQ total score from 0 to < 39 was found to represent a mild effect, ≥ 39 to < 59 a moderate effect, and ≥ 59 to 100 a severe effect.Conclusion.The analysis indicates that a 14% change in the FIQ total score is clinically relevant, and results of these analyses should enhance the clinical utility of the FIQ in research and practice.

scholarly journals Eptinezumab for the prevention of chronic migraine: efficacy and safety through 24 weeks of treatment in the phase 3 PROMISE-2 (Prevention of migraine via intravenous ALD403 safety and efficacy–2) study

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Stephen Silberstein ◽  
Merle Diamond ◽  
Nada A. Hindiyeh ◽  
David M. Biondi ◽  
Roger Cady ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Patient Reported Outcomes ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Patient Global Impression ◽  
Calcitonin Gene ◽  
Patient Reported ◽  
Global Impression Of Change

Abstract Background PROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of repeat intravenous (IV) doses of the calcitonin gene-related peptide–targeted monoclonal antibody eptinezumab (ALD403) for migraine prevention in adults with chronic migraine. This report describes the results of PROMISE-2 through 24 weeks of treatment. Methods Patients received up to two 30-min IV administrations of eptinezumab 100 mg, 300 mg, or placebo separated by 12 weeks. Patients recorded migraine and headache endpoints in a daily eDiary. Additional assessments, including patient-reported outcomes, were performed at regularly scheduled clinic visits throughout the 32-week study period (screening, day 0, and weeks 2, 4, 8, 12, 16, 20, 24, and 32). Results A total of 1072 adults received treatment: eptinezumab 100 mg, n = 356; eptinezumab 300 mg, n = 350; placebo, n = 366. The reduction in mean monthly migraine days observed during the first dosing interval (100 mg, − 7.7 days; 300 mg, − 8.2 days; placebo, − 5.6 days) was further decreased after an additional dose (100 mg, − 8.2 days; 300 mg, − 8.8 days; placebo, − 6.2 days), with both doses of eptinezumab demonstrating consistently greater reductions from baseline compared to placebo. The ≥50% and ≥ 75% migraine responder rates (MRRs) increased after a second dose, with more eptinezumab-treated patients experiencing migraine response than placebo patients (≥50% MRRs weeks 13–24: 100 mg, 61.0%; 300 mg, 64.0%; placebo, 44.0%; and ≥ 75% MRRs weeks 13–24: 100 mg, 39.3%; 300 mg, 43.1%; placebo, 23.8%). The percentages of patients who improved on patient-reported outcomes, including the Headache Impact Test and Patient Global Impression of Change, increased following the second dose administration at week 12, and were greater with eptinezumab than with placebo at all time points. No new safety concerns were identified with the second dose regarding the incidence, nature, and severity of treatment-emergent adverse events. Conclusion Eptinezumab 100 mg or 300 mg administered IV at day 0 and repeated at week 12 provided sustained migraine preventive benefit over a full 24 weeks and demonstrated an acceptable safety profile in patients with chronic migraine. Trial registration ClinicalTrials.gov (Identifier: NCT02974153). Registered November 23, 2016.

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