Objective. To assess the efficacy and safety of pramipexole, a dopamine 3 receptor agonist, in patients with fibromyalgia.Methods. In this 14-week, single-center, doubleblind, placebo-controlled, parallel-group, escalatingdose trial, 60 patients with fibromyalgia were randomized 2:1 (pramipexole:placebo) to receive 4.5 mg of pramipexole or placebo orally every evening. The primary outcome was improvement in the pain score (10-cm visual analog scale [VAS]) at 14 weeks. Secondary outcome measures were the Fibromyalgia Impact Questionnaire (FIQ), the Multidimensional Health Assessment Questionnaire (MDHAQ), the pain improvement scale, the tender point score, the 17-question Hamilton Depression Inventory (HAM-d), and the Beck Anxiety Index (BAI). Patients with comorbidities and disability were not excluded. Stable dosages of concomitant medications, including analgesics, were allowed.Results. Compared with the placebo group, patients receiving pramipexole experienced gradual and more significant improvement in measures of pain, fatigue, function, and global status. At 14 weeks, the VAS pain score decreased 36% in the pramipexole arm and 9% in the placebo arm (treatment difference -1.77 cm). Forty-two percent of patients receiving pramipexole and 14% of those receiving placebo achieved >50% decrease in pain. Secondary outcomes favoring pramipexole over placebo included the total FIQ score (treatment difference -9.57) and the percentages of improvement in function (22% versus 0%), fatigue (29% versus 7%), and global (38% versus 3%) scores on the MDHAQ. Compared with baseline, some outcomes showed a better trend for pramipexole treatment than for placebo, but failed to reach statistical significance, including improvement in the tender point score (51% versus 36%) and decreases in the MDHAQ psychiatric score (37% versus 28%), the BAI score (39% versus 27%), and the HAM-d score (29% versus 9%). No end points showed a better trend for the placebo arm. The most common adverse events associated with pramipexole were transient anxiety and weight loss. No patient withdrew from the study because of inefficacy or an adverse event related to pramipexole.Conclusion. In a subset of patients with fibromyalgia, ϳ50% of whom required narcotic analgesia and/or were disabled, treatment with pramipexole improved scores on assessments of pain, fatigue, function, and global status, and was safe and well-tolerated.Abnormal autonomic arousal (1-4), altered sleep stage architecture (5), chronic pain, and fatigue characterize fibromyalgia syndrome. The pathogenesis of fibromyalgia is a matter of debate, but centrally mediated abnormalities of sensory processing play an important role (6). Clinicians have tried various pharmacotherapies, including such agents as antidepressants, antiepileptics, muscle relaxants, antiinflammatories, sedative hypnotics, analgesics, and nutriceuticals (7). As a central neurotransmitter, dopamine influences human behavior, autonomic arousal, and sleep (8). Discovery of dopamine receptor subtypes (D 1-5 ) and thei...
This 14-week, phase 3, double-blind, randomized, controlled trial evaluated sodium oxybate (SXB) 4.5 and 6g per night versus placebo in patients with fibromyalgia (FM). SXB is the sodium salt of γ-hydroxybutyrate (GHB). GHB is an endogenous compound, synthesized from γ-aminobutyric acid (GABA) and found broadly in the central nervous system and body. Among 548 randomized patients, a ≥30% reduction in pain was experienced by 54.2% and 58.5% of patients treated with SXB 4.5 and 6g, respectively, versus 35.2% for placebo with a 100-mm Visual Analog Scale (VAS) (P<0.001 for both comparisons). Relative to placebo, both SXB doses significantly reduced fatigue (with a 100-mm VAS; P<0.001) and sleep disturbance (with the Jenkins Sleep Scale; P<0.001), and resulted in significant improvements in function as measured by the FM Impact Questionnaire (P=0.003 and P=0.001 for 4.5 and 6 g per night, respectively). On the Short-Form 36 Health Survey, SXB-related improvement was significant on the Physical, but not the Mental, Component Scale. The proportion of patients who reported a global improvement of "much" or "very much" better on the Patient Global Impression of Change was significantly greater in both SXB groups versus placebo (P<0.001). Headache, nausea, dizziness, vomiting, diarrhea, anxiety, and sinusitis were the most commonly reported adverse events, with an incidence at least twice that of placebo. These results expand the evidence from previous clinical trials suggesting that SXB is effective and safe in FM.
While biologic aspects of PD and FM differ considerably, compulsive gambling and shopping have become important, yet unexpected concerns related to use of dopamine agonists for patients with FM and their treating clinicians.
Fibromyalgia is a common disorder that is characterized by chronic widespread pain, tenderness to light palpation, fatigue and sleep disturbances. The present lack of a well-accepted model of the disorder has hampered progress towards adequate treatment. A review of potential models to explain the pathophysiology underlying its primary symptom (i.e., chronic widespread pain) lends insight on the therapeutic potential of novel therapies. Following this, a mechanistic evaluation of those medications that are under consideration for the treatment of the disorder is offered. Adequate treatment will be likely to involve the identification of biologic subgroups within the greater fibromyalgia construct. Key insights from basic research are the basis for increased optimism for effective relief among patients and clinicians.
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