Mease, P.J. et al., "The Efficacy and Safety of Milnacipran for Treatment of Fibromyalgia. A Randomized, Double-blind, Placebo-controlled Trial"

Mease, P.J. et al., "The Efficacy and Safety of Milnacipran for Treatment of Fibromyalgia. A Randomized, Double-blind, Placebo-controlled Trial," J. Rheumatol Dec 15 (2008). [Epub ahead of print] PMID: 19132781

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 (real-time, 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.

Cordero, M.D. et al., "Coenzyme Q10 Distribution in Blood is Altered in Patients with Fibromyalgia"

Cordero, M.D. et al., "Coenzyme Q10 Distribution in Blood is Altered in Patients with Fibromyalgia," Clin Biochem 42, Nos. 7-8 (2009): 732-735. 

Objective. Coenzyme Q-10 (CoQ (10)) is an essential electron carrier in the mitochondrial respiratory chain and a strong antioxidant. Signs and symptoms associated with muscular alteration and mitochondrial dysfunction, including oxidative stress, have been observed in patients with fibromyalgia (FM). The aim was to study CoQ (10) levels in plasma and mononuclear cells, and oxidative stress in FM patients.

Methods. We studied CoQ (10) level by HPLC in plasma and peripheral mononuclear cells obtained from patients with FM and healthy control subjects. Oxidative stress markers were analyzed in both plasma and mononuclear cells from FM patients.

Results. Higher level of oxidative stress markers in plasma was observed in FM patients in respect to control subjects. CoQ (10) level in plasma samples from FM patients was doubled compared to healthy controls, and in blood mononuclear cells isolated from 37 FM patients was found to be about 40% lower. Higher levels of reactive oxygen species (ROS) production was observed in mononuclear cells from FM patients compared to controls, and a significant decrease was induced by the presence of CoQ (10). [N.B. ROS are produced when cells are under oxidative stress. They damage cells.]

Conclusion. The distribution of CoQ (10) in blood components was altered in FM patients. Also, our results confirm the oxidative stress background of this disease probably due to a defect on the distribution and metabolism of CoQ (10) in cells and tissues. The protection caused in mononuclear cells by CoQ (10) would indicate the benefit of its supplementation in FM patients.

Pamuk, O.N. et al., "Increased Frequencies of Hysterectomy and Early Menopause in Fibromyalgia Patients: A Comparative Study"

Pamuk, O.N. et al., "Increased Frequencies of Hysterectomy and Early Menopause in Fibromyalgia Patients: A Comparative Study," Clin Rheumatol Jan 24 (2009). [Epub ahead of print] PMID: 19169621

Methods and Results. The objective was to determine the relationship between symptoms of fibromyalgia (FM) and early menopause and hysterectomy.

We included 115 postmenopausal patients with FM (mean age 54.6 +/- 7.6) and 67 rheumatoid arthritis (RA) patients (mean age 55.5 +/- 9) into our study. All patients were questioned about the severity of their symptoms of FM, anxiety, and depression by using a visual analog scale and FM impact questionnaire. Patients' history of menopause and hysterectomy were recorded.

Menopause at age less than 45 years was accepted to mean "early". The frequencies of early menopause (38.3% vs. 13.4%, p < 0.001) and hysterectomy (16.5% vs. 6%, p 0.05). FM-related symptoms started in 30 patients (26.1%) with FM with menopause or within the first postmenopausal year. When the clinical features of FM patients whose symptoms started within the first menopausal year were compared to other FM patients; it was observed that the frequency of early menopause was higher in the former group (p < 0.048). The Duke anxiety and depression score was higher in patients with hysterectomy whose FM symptoms started within the first year of post-hysterectomy than other FM patients (9.1 +/- 2.7 vs. 6.7 +/-2.7, p < 0.022).

Conclusion. Early menopause and hysterectomy may be one of the factors contributing to the development of FM.

Wang, H. et al., "The Role of IL-8 in Patients with Fibromyalgia: A Prospective Longitudinal Study of 6 Months"

Wang, H. et al., "The Role of IL-8 in Patients with Fibromyalgia: A Prospective Longitudinal Study of 6 Months," Clin J Pain 25 (1) (2009): 1-4. PMID: 19158539

(Note: IL-8 or Interleukin-8 is a chemical with an important role in the immune system.)

Methods. IL-8 in sera was measured in 20 patients with FM undergoing pain treatment and 80 healthy participants at 4 fixed time points: at the beginning of the study, at 10 days, 21 days, and 6 months, respectively. Pain intensity, back function, depression, nicotine/alcohol consumption, and medication were assessed in the patient group and correlated with IL-8 levels.

Results. Before and during the inpatient therapy, the serum level of IL-8 was significantly higher in patients with FM compared with controls (P<0.001), but did not correlate with pain intensity and medication. Already at ten days into the study there was a significant reduction of IL-8 serum level (P=0.023) in the patient group. Six months after multidisciplinary pain therapy, IL-8 serum level in FM patients was still significantly higher than controls (P=0.044) but reduced approximately to normal range and correlated significantly negatively with pain intensity (r=-0.782, P=0.001). Patients with FM had significantly less pain (P<0.001) and better back function (P<0.001) at day 2 than at day 0. In addition, in patients with FM, IL-8 serum level correlated with nicotine consumption (r=0.471, P=0.042).

Conclusions. Our results suggest that IL-8 level contributes in patients with FM, but their pain intensity and back function can be improved under influence of multidisciplinary pain therapy without need of an anti-IL-8 therapy.

Jones, K.D. et al., "Fibromyalgia is Associated with Impaired Balance and Falls"

Jones, K. D. et al., "Fibromyalgia is Associated with Impaired Balance and Falls," J Clin Rheumatol 15(1) (2009): 16-21. PMID: 19125137

Methods. Thirty-four FM patients and 32 age-matched controls were administered the Balance Evaluation-Systems Test (BESTest), rated their balance confidence with the Activities-Specific Balance Confidence (ABC) Scale, and reported the number of falls in the last 6 months. The Fibromyalgia Impact Questionnaire was used to assess FM severity.

Results. FM patients had significantly impaired balance in all components of the BESTest compared with controls. They also scored more poorly on balance confidence. Overall FM severity (Fibromyalgia Impact Questionnaire) correlated significantly with the BESTest and the ABC scale. The BESTest and ABC correlated significantly with 6 commonly reported FM symptoms (excluding pain). FM patients reported a total of 37 falls over the last 6-months compared with 6 falls in healthy controls.

Conclusion. FM is associated with balance problems and increased fall frequency. Patients were aware of their balance problems. These results suggest that FM may affect peripheral and/or central mechanisms of postural control. Further objective study is needed to identify the relative contributions of various neural and musculoskeletal and other impairments to postural stability in FM to provide clinicians with methods to maximize postural stability and help fall prevention.