While no clinical trial to date has specifically targeted fatigue , r and omized controlled trials , systematic review s , and meta-analyses indicate that treatment modalities studied in the context of other fibromyalgia symptoms could also improve fatigue .
Fatigue is a disabling , multifaceted symptom that is highly prevalent and stubbornly persistent .
Although fatigue is a frequent complaint among patients with fibromyalgia , it has not received the same attention as pain .
Reasons for this include lack of st and ardized nomenclature to communicate about fatigue , lack of evidence -based guidelines for fatigue assessment , and a deficiency in effective treatment strategies .
Fatigue does not occur in isolation ; rather , it is present concurrently in varying severity with other fibromyalgia symptoms such as chronic widespread pain , unrefreshing sleep , anxiety , depression , cognitive difficulties , and so on .
Survey-based and preliminary mechanistic studies indicate that multiple symptoms feed into fatigue and it may be associated with a variety of physiological mechanisms .
Safety and efficacy of esreboxetine in patients with fibromyalgia: An 8-week, multicenter, randomized, double-blind, placebo-controlled study.
BACKGROUND Esreboxetine is an investigational , highly selective norepinephrine reuptake inhibitor that has been reported to have antinociceptive effects in pre clinical pain models . OBJECTIVE This study assessed the efficacy and safety profile of esreboxetine in the management of fibromyalgia . METHODS This was a multicenter , r and omized , double-blind , placebo-controlled trial in patients aged ≥18 years who met American College of Rheumatology criteria for fibromyalgia . Eligible patients were required to have a score ≥40 mm on the 100-mm visual analog scale of the Short-Form McGill Pain Question naire at screening and r and omization , and a mean score ≥4 on an 11-point pain rating scale ( from 0 = no pain to 10 = worst possible pain ) based on the weekly mean pain score in the week before r and omization . After a 1-week baseline period and a 2-week , single-blind , placebo run-in period , patients were r and omized to receive esreboxetine or placebo for 8 weeks , followed by a 1-week follow-up period . Esreboxetine dosing was started at 2 mg/d and was escalated by 2 mg/d every 2 weeks until attainment of a dose of 8 mg/d or the maximum tolerated dose . The primary efficacy outcome was the change from baseline to week 8 in weekly mean pain scores , as derived from patients ' daily pain ratings on the 11-point scale . Additional primary efficacy outcomes included changes in the Fibromyalgia Impact Question naire ( FIQ ) total score and the Patient Global Impression of Change ( PGIC ) . The safety profile was evaluated based on observed and spontaneously reported adverse events , laboratory tests , and other safety measures . RESULTS One hundred thirty-four patients were r and omized to each study group , but 1 patient in the placebo group did not receive treatment . Thus , the study population consisted of 267 patients ( 89.5 % female ; 88.4 % white ; mean age , ∼50 years [ range , 20 - 84 years ] ) . Twenty-seven patients in each group discontinued the study . Adverse events were the most common reason for discontinuation in the esreboxetine group ( 11 patients ) , compared with 3 discontinuing due to adverse events in the placebo group . Patient default ( withdrawal of consent and loss to follow-up ) was the most common reason for discontinuation in the placebo group ( 13 patients ) , compared with 10 in the esreboxetine group . The esreboxetine group had significantly greater improvement in the weekly mean pain score compared with the placebo group ( mean [ SE ] change from baseline : -1.55 [ 0.16 ] vs -0.99 [ 0.16 ] , respectively ; P = 0.006 ) . A significantly greater percentage of patients in the esreboxetine group reported a ≥30 % reduction in pain scores compared with the placebo group ( 37.6 % [ 50/133 ] vs 22.6 % [ 30/133 ] ; P = 0.004 ) . Esreboxetine was associated with significant improvement compared with placebo in the FIQ total score ( mean change from baseline : -15.63 [ 1.56 ] vs -8.07 [ 1.54 ] ; P < 0.001 ) . On the PGIC , significantly more patients in the esreboxetine group than in the placebo group reported their condition much or very much improved ( odds ratio = 2.42 ; 90 % CI , 1.549 - 3.786 ; P < 0.001 ) . Esreboxetine also was associated with significant improvements in secondary outcomes compared with placebo . These included fatigue , as reflected in scores on the Multidimensional Assessment of Fatigue ( mean [ SE ] change from baseline : -6.39 [ 0.75 ] vs -2.82 [ 0.75 ] , respectively ; P < 0.001 ) , and scores on measures of patient function and health-related quality of life , including the 36-item Short Form Health Survey ( SF-36 ) Physical Component Summary ( mean change from baseline : 4.36 [ 0.59 ] vs 1.86 [ 0.59 ] ; P = 0.002 ) , the SF-36 Mental Component Summary ( mean change from baseline : 4.25 [ 0.83 ] vs 1.81 [ 0.83 ] ; P = 0.019 ) , and the Sheehan Disability Scale total score ( mean change from baseline : -6.50 [ 0.64 ] vs -2.79 [ 0.61 ] ; P < 0.001 ) . Numerically more patients in the esreboxetine group than in the placebo group reported at least one adverse event ( 71.6 % vs 57.1 % ) , most commonly constipation ( 17.2 % vs 5.3 % ) , insomnia ( 15.7 % vs 3.0 % ) , dry mouth ( 15.7 % vs 2.3 % ) , and headache ( 10.4 % vs 2.3 % ) . CONCLUSIONS In this 8-week trial in patients with fibromyalgia , esreboxetine was associated with significant reductions in pain scores compared with placebo . It was also associated with improvements in outcomes relevant to fibromyalgia , including the PGIC , function , and fatigue . Clinical Trials.gov identifier : NCT00357825
While no clinical trial to date has specifically targeted fatigue , r and omized controlled trials , systematic review s , and meta-analyses indicate that treatment modalities studied in the context of other fibromyalgia symptoms could also improve fatigue .
Fatigue is a disabling , multifaceted symptom that is highly prevalent and stubbornly persistent .
Although fatigue is a frequent complaint among patients with fibromyalgia , it has not received the same attention as pain .
Reasons for this include lack of st and ardized nomenclature to communicate about fatigue , lack of evidence -based guidelines for fatigue assessment , and a deficiency in effective treatment strategies .
Fatigue does not occur in isolation ; rather , it is present concurrently in varying severity with other fibromyalgia symptoms such as chronic widespread pain , unrefreshing sleep , anxiety , depression , cognitive difficulties , and so on .
Survey-based and preliminary mechanistic studies indicate that multiple symptoms feed into fatigue and it may be associated with a variety of physiological mechanisms .