Fibromyalgia: Moldofsky H

Brosseau L, Wells GA, Tugwell P, Egan M, Wilson KG, Dubouloz CJ, Casimiro L, Robinson VA, McGowan J, Busch A, Poitras S, Moldofsky H, Harth M, Finestone HM, Nielson W, Haines-Wangda A, Russell-Doreleyers M, Lambert K, Marshall AD, Veilleux L, Anonymous00378. · Clinical Epidemiology Unit, Ottawa Hospital Research Institute, Ottawa Hospital, Civic Campus, Ottawa, Ontario, Canada. · Phys Ther. · Pubmed #18497302 links to  free full text

Abstract: BACKGROUND AND PURPOSE: The objective of this study was to create guidelines for the use of strengthening exercises in the management of adult patients (>18 years of age) with fibromyalgia (FM), as defined by the 1990 American College of Rheumatology criteria. METHODS: Following Cochrane Collaboration methods, the Ottawa Methods Group found and synthesized evidence from comparative controlled trials and formed the Ottawa Panel, with nominated experts from key stakeholder organizations. The Ottawa Panel then developed criteria for grading the recommendations based on experimental design (I for randomized controlled trials, II for nonrandomized studies) and strength of evidence (A, B, C+, C, D+, D, or D-). From the rigorous literature search, 5 randomized controlled trials were selected. Statistical analysis was based on Cochrane Collaboration methods. Continuous data were calculated with weighted mean differences between the intervention and control groups, and dichotomous data were analyzed with relative risks. Clinical improvement was calculated using absolute benefit and relative difference in change from baseline. Clinical significance was attained when an improvement of 15% relative to a control was found. RESULTS: There were 5 positive recommendations: 2 grade A and 3 grade C+. All 5 were of clinical benefit. DISCUSSION AND CONCLUSION: The Ottawa Panel recommends strengthening exercises for the management of fibromyalgia as a result of the emerging evidence (grades A, B, and C+, although most trials were rated low quality) shown in the literature.

Brosseau L, Wells GA, Tugwell P, Egan M, Wilson KG, Dubouloz CJ, Casimiro L, Robinson VA, McGowan J, Busch A, Poitras S, Moldofsky H, Harth M, Finestone HM, Nielson W, Haines-Wangda A, Russell-Doreleyers M, Lambert K, Marshall AD, Veilleux L, Anonymous00377. · Clinical Epidemiology Unit, Ottawa Hospital Research Institute, Ottawa Hospital, Civic Campus, Ottawa, Ontario, Canada. · Phys Ther. · Pubmed #18497301 links to  free full text

Abstract: BACKGROUND AND PURPOSE: The objective of this study was to create guidelines for the use of aerobic fitness exercises in the management of adult patients (>18 years of age) with fibromyalgia, as defined by the 1990 American College of Rheumatology criteria. METHODS: Following Cochrane Collaboration methods, the Ottawa Methods Group found and synthesized evidence from comparative controlled trials and formed the Ottawa Panel, with nominated experts from key stakeholder organizations. The Ottawa Panel then developed criteria for grading the recommendations based on experimental design (I for randomized controlled trials, II for nonrandomized studies) and strength of evidence (A, B, C+, C, D+, D, or D-). From the rigorous literature search, 13 randomized control trials and 3 controlled clinical trials were selected. Statistical analysis was based on Cochrane Collaboration methods. Continuous data were calculated with weighted mean differences between the intervention and control groups, and dichotomous data were analyzed with relative risks. Clinical improvement was calculated using absolute benefit and relative difference in change from baseline. Clinical significance was attained when an improvement of 15% relative to a control was found. RESULTS: There were 24 positive recommendations: 10 grade A, 1 grade B, and 13 grade C+. Of these 24 positive recommendations, only 5 were of clinical benefit. DISCUSSION AND CONCLUSION: The Ottawa Panel recommends aerobic fitness exercises for the management of fibromyalgia as a result of the emerging evidence (grades A, B, and C+, although most trials were rated low quality) shown in the literature.

Moldofsky H. · Faculty of Medicine, University of Toronto, Sleep Disorders Clinic of the Centre for Sleep and Chronobiology, 340 College Street, Suite 580, Toronto, ON MST 3A9, Canada. · Joint Bone Spine. · Pubmed #18456536 No free full text.

Abstract: The clinical focus of rheumatologists on the widespread pain and numerous tender points in specific anatomic regions in their patients who show no evidence for disease pathology has lead to the characterization of such peripheral symptoms as a specific disorder of the musculoskeletal system, now commonly known as fibromyalgia. This rheumatologic diagnostic entity has resulted in relative inattention to an understanding of their patients' common complaints of unrefreshing sleep, chronic fatigue and psychological distress. Experimental evidence from humans and animal studies indicate that there is an inter-relationship of disturbances in the physiology of the sleeping-waking brain with the widespread musculoskeletal pain, chronic fatigue, and psychological distress in patients with hitherto unexplained pain/fatigue illnesses, e.g., fibromyalgia and chronic fatigue syndromes. The emerging knowledge of the dysfunction of the nervous system in such patients has lead to the study of novel medications that affect neurotransmitter functions, e.g., pregabalin, serotonin/noradrenaline compounds and sodium oxybate that are shown to improve many of the symptoms of such patients.

Moldofsky H. · Sleep Disorders Clinic of the Centre for Sleep and Chronobiology, Toronto, Ontario, Canada. · CNS Spectr. · Pubmed #18323770 links to  free full text

Abstract: People with fibromyalgia syndrome (FMS) experience unrefreshing sleep, aches, hypersensitivity, and cognitive and emotional difficulties. Although no specific causative factor or biological agent is known to account for all of the features of FMS and these related diagnoses, the generalized hypersensitivity of the body is considered to be affected by disturbances in central nervous system (CNS) functions. Such CNS disturbances are intrinsic to the sleeping-waking brain, where the common symptom elements in all these illnesses are poor quality of sleep, nonspecific pain, fatigue, and psychological distress in the absence of known disease pathology.

Benca RM, Ancoli-Israel S, Moldofsky H. · University of Wisconsin, Madison, USA. · J Clin Psychiatry. · Pubmed #15153065 No free full text.

Abstract: Patients with insomnia who also have chronic pain or depression or who are elderly represent segments of the population that are particularly difficult to treat. These populations tend to be at higher risk for experiencing difficulty sleeping and are more likely to experience chronic insomnia, sleep maintenance problems, and/or nonrestorative sleep. Worsening insomnia may exacerbate other somatic and psychological symptoms and vice versa. Conversely, there is evidence that appropriate recognition and management of the sleep complaint may alleviate other symptoms related to the associated condition and help interrupt this vicious cycle.

Moldofsky H. · Sleep Disorders Clinic of the Centre for Sleep and Chronobiology, 340 College Street, Suite 580, Toronto, ON M5T 3A9, Canada. · Rheum Dis Clin North Am. · Pubmed #12122923 No free full text.

Abstract: In summary, the treatment of patients with FM requires a proper assessment of the reason for the unrefreshing sleep, which is an important component of the FM syndrome. Sleep laboratory investigations provides a suitable rationale for management where a specific primary sleep disorder is determined. Nonspecific treatments include various behavioral approaches to improve sleep hygiene, fitness, and regular proper nutrition that serve to regularize disturbances in circadian sleep-wake rhythms. As yet, no medication is known to improve the EEG sleep arousal disorders that include phasic (alpha-delta), tonic alpha non-REM sleep disorders, or the periodic K alpha cycling alternating pattern disorder. Traditional hypnotic agents, while helpful in initiating and maintaining sleep and reducing daytime tiredness, do not provide restorative sleep or reduce pain. Tricyclic drugs, such as amitriptyline and cyclobenzaprine, may provide long term benefit for improving sleep but may not have a continuing benefit beyond one month for reducing pain. The use of a biologic agent that facilitates sleep-related neuroendocrine functions, for example growth hormone, is reported to improve symptoms but the need for injection and high cost restrict its use. No systematic studies have been reported on the use of remedial measures for the management of PLMS/restless legs syndrome and sleep apnea that occur in some patients with FM.

Chappell AS, Littlejohn G, Kajdasz DK, Scheinberg M, D'Souza DN, Moldofsky H. · Lilly Research Laboratories, Eli Lilly and Co, Indianapolis, IN 46285, USA. · Clin J Pain. · Pubmed #19454869 No free full text.

Abstract: OBJECTIVES: Evaluate the efficacy and safety of duloxetine at doses up to 120 mg once daily in patients with fibromyalgia. METHODS: This was a phase 3, 60-week study, which included an 8-week open-label period followed by a 52-week, randomized, double-blind period. Patients received duloxetine 30 mg daily for 1 week and duloxetine 60 mg daily for 7 weeks and were then randomized to receive either 60 or 120 mg daily (1:2 ratio). RESULTS: Enrolled patients (N=350, 95.7% female) exhibited moderate disease symptoms at study entry (Brief Pain Inventory average pain=6.7, Clinical Global Impression of Severity=4.1, and Patient's Global Impression of Severity=4.1). Significant pain reduction in patients was observed during the open-label study phase. This pain reduction continued during the 52-week double-blind study phase, as demonstrated by additional mean decreases in the Brief Pain Inventory average pain score within both duloxetine groups. The most common (> or =15%) treatment-emergent adverse events (overall phase) were nausea, headache, insomnia, dizziness, constipation, and dry mouth. Seventy-four (21.1%) patients reported adverse events as a reason for discontinuation [most common (>1%) were insomnia, vomiting, diarrhea, dizziness, and nausea]. The mean change (SD) in sitting systolic blood pressure (mm Hg) was -0.1 (14.4), in sitting diastolic blood pressure was -0.2 (9.6), in sitting pulse rate was 1.9 (10.4) bpm, and in weight was 0.7 (4.3) kg. DISCUSSION: The profile of duloxetine for the long-term treatment of fibromyalgia was consistent with that seen in other indications for which the drug is currently marketed.

Iaboni A, Ibanez D, Gladman DD, Urowitz MB, Moldofsky H. · University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada. · J Rheumatol. · Pubmed #17143980 No free full text.

Abstract: OBJECTIVE: To clarify the role of sleep disorders, sleepiness, and depression in patients with systemic lupus erythematosus (SLE) who complain of disabling tiredness. METHODS: Patients with SLE (31 women, 4 men) with disabling tiredness were evaluated with the Epworth Sleepiness Scale (ESS) and overnight polysomnography, followed by daytime multiple sleep latency tests (MSLT) and the Beck Depression Inventory (BDI). Their polysomnography was compared with 17 healthy, asymptomatic controls. RESULTS: Polysomnography of the patients in comparison with healthy controls showed impaired sleep efficiency (p < 0.02), high arousal frequencies (p < 0.01), increased stage 1 sleep (p < 0.02), decreased stage 3/4 slow-wave sleep (p < 0.02), and a high percentage (77% of patients) with increased alpha-EEG non-REM sleep. In 23% of patients periodic limb movement (PLM) disorder was observed (mean PLM index 31.1 +/- 15); 26% of patients had obstructive sleep apnea (mean apnea/hypopnea index 19.3 +/- 10), and one patient had narcolepsy-cataplexy. Remarkably, 51% of patients were excessively sleepy on both the ESS and MSLT (mean sleep latency < 10 min). This excessive daytime sleepiness was not related to sleep restriction. There was no association between sleepiness and SLE disease features such as neuropsychiatric SLE, medications, fibromyalgia, or disease activity. As a whole, the study group reported mild to moderate depression (mean BDI = 15.8 +/- 9.9). Within the group, the sleepy patients had lower BDI scores than the non-sleepy patients (p < 0.02), and fewer of the sleepy patients were depressed (p < 0.04). CONCLUSION: Primary sleep disorders, sleepiness, and depression are common in tired SLE patients. Tiredness in SLE that is the result of excessive daytime sleepiness can be distinguished from tiredness of depression. Such distinctions will help identify appropriate treatment for tired patients with SLE.

Hawley DJ, Wolfe F, Lue FA, Moldofsky H. · National Data Bank for Rheumatic Diseases--Arthritis Research Center Foundation, Wichita, KS 67214, USA. · J Rheumatol. · Pubmed #11508598 No free full text.

Abstract: OBJECTIVE: To examine the nature of seasonal symptoms, their prevalence, and differences among rheumatic disorders by examining longitudinal data over a period of up to 24 years. METHODS: We used a questionnaire assessment of seasonal symptoms using the Seasonal Pattern Assessment Questionnaire (SPAQ) in 1,424 patients with rheumatoid arthritis (RA), osteoarthritis (OA), and fibromyalgia (FM). Clinical status was evaluated with standard assessment measures, and reported symptoms were compared with actual seasonal differences measured for periods of up to 24 years. RESULTS: About 50% of patients with rheumatic disease reported exacerbation of rheumatic symptoms (pain, global severity, and fatigue) by seasonal changes. The presence of seasonal symptoms was not related to diagnosis or to seasonal affective disorder (SAD) symptoms, and symptoms were less common in older patients and in men. The number of symptoms and the severity of allied factors (depression, anxiety, pain, global severity, number of months with seasonal symptoms) were increased in persons with FM and/or complete SAD symptoms. Using circular statistics, the modal months for worse symptoms were December and January, and for best symptoms was July. Bimodal patterns of seasonality were identified for global severity, joint pain, fatigue, and socialization. Seasonal symptoms differed as to the degree at which they were dispersed around the 12 month circle. When pain and global severity measurements obtained over a 24 year period were analyzed, pain was slightly increased in the summer and global severity was not related to season at all. Even when patients who specifically reported worse symptoms in winter and best symptoms in summer were examined, no effect of season could be found. CONCLUSION: Seasonal rheumatic symptoms are commonly reported across all rheumatic diseases, but appear to reflect perception rather than reality since reported symptoms do not agree with measured clinical scores. In addition, regardless of seasonal complaints, measured pain and global severity scores are not worse in winter. Although patients with FM and Season (+) patients report more severe symptoms, their pattern of reporting and their actual scores do not differ according to season compared to persons without FM or positive seasonality.

Roizenblatt S, Moldofsky H, Benedito-Silva AA, Tufik S. · Departamento de Psicobiologia, São Paulo Federal University, Brazil. · Arthritis Rheum. · Pubmed #11212164 links to  free full text

Abstract: OBJECTIVE: To characterize the patterns of alpha electroencephalographic sleep and their associations with pain and sleep in patients with fibromyalgia. METHODS: Pain and sleep symptoms of 40 female patients with fibromyalgia and 43 healthy control subjects were studied before and after overnight polysomnography. Blinded analyses of alpha activity in non-rapid eye movement (non-REM) sleep were performed using time domain, frequency domain, and visual analysis techniques. RESULTS: Three distinct patterns of alpha sleep activity were detected in fibromyalgia: phasic alpha (simultaneous with delta activity) in 50% of patients, tonic alpha (continuous throughout non-REM sleep) in 20% of patients, and low alpha activity in the remaining 30% of patients. Low alpha activity was exhibited by 83.7% of control subjects (P < 0.01). All fibromyalgia patients who displayed phasic alpha sleep, activity reported worsening of pain after sleep, compared with 58.3% of patients with low alpha activity (P < 0.01) and 25.0% of patients with tonic alpha activity (P < 0.01). Postsleep increase in the number of tender points occurred in 90.0% of patients with phasic alpha activity, 41.7% of patients with low alpha activity, and 25.0% of patients with tonic alpha activity (P < 0.01). Self ratings of poor sleep were reported by all patients with phasic alpha activity, 58.3% of patients with low alpha activity (P < 0.01), and 12.5% of patients with tonic alpha activity (P < 0.01). Patients with phasic alpha activity reported longer duration of pain than patients in other subgroups (P < 0.01). Additionally, patients with phasic alpha sleep activity exhibited less total sleep time than patients in other subgroups (P < 0.05), as well as lower sleep efficiency (P < 0.05) and less slow wave sleep (P < 0.05) than patients with a tonic alpha sleep pattern. CONCLUSION: Alpha intrusion during sleep can be of different patterns. Phasic alpha sleep activity was the pattern that correlated better with clinical manifestations of fibromyalgia.