A randomized, double‐blind, placebo‐controlled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications

Abstract

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...

Quetiapine Fumarate Extended‐Release for the Treatment of Major Depression With Comorbid Fibromyalgia Syndrome: A Double‐Blind, Randomized, Placebo‐Controlled Study

“…Similar findings were observed in a pooled analysis of 2 randomized, placebo-controlled trials of milnacipran monotherapy for the treatment of fibromyalgia (21). Dopaminergic agonists including pramipexole (22) and ropinirole (23) have been shown to be effective in the treatment of fibromyalgia, lending further support to the role of dopamine in the etiology of fibromyalgia.…”

Animal Models of Fibromyalgia

“…Duloxetine has been shown to significantly recover muscle hyperalgesia but not tactile allodynia in RIM rats. Further, the dopamine receptor agonist pramipexole has been shown to be efficacious in treating fibromyalgia pain symptoms in a phase II clinical study (Holman and Myers, 2005). In line with this, pramipexole attenuates muscle hyperalgesia and tactile allodynia at doses that cause hyper-locomotion in RIM rats.…”

Fibromiyaljide Farmakolojik Tedavi

“…Bu sebeple pramipeksol, ropinirol ve rotigotin gibi dopamin agonistleri fibromiyalji tedavisinde klinik çalışmalar ile araştırılmıştır. Birden fazla ilacın kombine kullanıldığı 12 haftalık bir çalışmanın sonuçlarına göre pramipeksol'ün Fibromiyalji Etki Anketi (FIQ) ve Çok Yönlü Sağlık Değerlendirme Anketi skorlarında anlamlı düzelmeler sağladığı gösterilmiştir 71 . Avrupa'da pramipeksol fibromiyalji tedavisinde kullanılabilecek ilaçlar listesinde yer alsa da monoterapide etkinliğini kesin olarak kanıtlayacak çalışmalara ihtiyaç olduğu vurgulanmıştır 72 .…”