David Baxter PhD
Late Founder
Pramipexole May Decrease Fibromyalgia Symptoms
July 28, 2005
by Laurie Barclay, MD
Pramipexole, a dopamine 3 receptor agonist, may decrease symptoms of fibromyalgia, according to the results of a randomized, double-blind trial reported in the August issue of Arthritis and Rheumatism.
"Blinded, placebo-controlled studies have demonstrated [pramipexole's] efficacy in the treatment of Parkinson's disease and restless legs syndrome," write Andrew J. Holman, MD, and Robin R. Myers, MS, ARNP, from Pacific Rheumatology Associates in Renton, Washington. "The cause of restless legs syndrome is unknown, but this arousal is more commonly found in patients with fibromyalgia than in healthy controls."
In this 14-week, parallel-group, escalating-dose trial, 60 patients with fibromyalgia were randomized 2:1 (pramipexole
lacebo) to receive either 4.5 mg of pramipexole or placebo orally every evening. Patients with comorbid conditions and disability were not excluded, and stable dosages of analgesics and other concomitant medications were permitted.
The main endpoint was improvement in the pain score (10-cm visual analog scale [VAS]) at 14 weeks, and secondary outcomes were scores on 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).
Compared with patients receiving placebo, those receiving pramipexole had gradual and more significant improvements in pain, fatigue, function, and global status. At 14 weeks, the VAS pain score decreased by 36% in the pramipexole group and by 9% in the placebo group (treatment difference, -1.77 cm). Decrease in pain by at least 50% occurred in 42% of patients receiving pramipexole and in 14% of those receiving placebo.
The pramipexole group also fared better than the placebo group in the total FIQ score (treatment difference, -9.57) and the percentages of improvement in function (22% vs 0%), fatigue (29% vs 7%), and global (38% vs 3%) scores on the MDHAQ. Compared with baseline, some outcomes showed a better trend with pramipexole than with placebo but did not reach statistical significance, including improvement in the tender point score (51% vs 36%) and decreases in the MDHAQ psychiatric score (37% vs 28%), the BAI score (39% vs 27%), and the HAM-d score (29% vs 9%).
Transient anxiety and weight loss were the most common adverse events reported with pramipexole. No patient withdrew from the study because of lack of efficacy or a pramipexole-related adverse event.
"In a subset of patients with fibromyalgia, [about] 50% 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," the authors write.
Study limitations include use of concomitant medications; inability to interpret why or how pramipexole may improve pain, fatigue, and function scores; insufficient power to predict which combination of concomitant medications might yield a positive response; short duration; inability to determine optimal dosage; and exclusion of patients with positional cervical myelopathy and untreated obstructive sleep apnea.
"In summary, a new treatment approach using a D3 [dopamine 3] receptor agonist offers hope to patients with fibromyalgia," the authors conclude. "Further investigation of this pramipexole treatment paradigm is warranted to determine its mechanism of action in patients with fibromyalgia, its long-term risks and benefits, and to confirm these findings in patients not taking concomitant medications."
Dr. Holman holds patents for the use of dopamine 2 and D3 receptor agonists in the treatment of fibromyalgia.
Arthritis Rheum. 2005;52:2495-2505
July 28, 2005
by Laurie Barclay, MD
Pramipexole, a dopamine 3 receptor agonist, may decrease symptoms of fibromyalgia, according to the results of a randomized, double-blind trial reported in the August issue of Arthritis and Rheumatism.
"Blinded, placebo-controlled studies have demonstrated [pramipexole's] efficacy in the treatment of Parkinson's disease and restless legs syndrome," write Andrew J. Holman, MD, and Robin R. Myers, MS, ARNP, from Pacific Rheumatology Associates in Renton, Washington. "The cause of restless legs syndrome is unknown, but this arousal is more commonly found in patients with fibromyalgia than in healthy controls."
In this 14-week, parallel-group, escalating-dose trial, 60 patients with fibromyalgia were randomized 2:1 (pramipexole
lacebo) to receive either 4.5 mg of pramipexole or placebo orally every evening. Patients with comorbid conditions and disability were not excluded, and stable dosages of analgesics and other concomitant medications were permitted.The main endpoint was improvement in the pain score (10-cm visual analog scale [VAS]) at 14 weeks, and secondary outcomes were scores on 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).
Compared with patients receiving placebo, those receiving pramipexole had gradual and more significant improvements in pain, fatigue, function, and global status. At 14 weeks, the VAS pain score decreased by 36% in the pramipexole group and by 9% in the placebo group (treatment difference, -1.77 cm). Decrease in pain by at least 50% occurred in 42% of patients receiving pramipexole and in 14% of those receiving placebo.
The pramipexole group also fared better than the placebo group in the total FIQ score (treatment difference, -9.57) and the percentages of improvement in function (22% vs 0%), fatigue (29% vs 7%), and global (38% vs 3%) scores on the MDHAQ. Compared with baseline, some outcomes showed a better trend with pramipexole than with placebo but did not reach statistical significance, including improvement in the tender point score (51% vs 36%) and decreases in the MDHAQ psychiatric score (37% vs 28%), the BAI score (39% vs 27%), and the HAM-d score (29% vs 9%).
Transient anxiety and weight loss were the most common adverse events reported with pramipexole. No patient withdrew from the study because of lack of efficacy or a pramipexole-related adverse event.
"In a subset of patients with fibromyalgia, [about] 50% 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," the authors write.
Study limitations include use of concomitant medications; inability to interpret why or how pramipexole may improve pain, fatigue, and function scores; insufficient power to predict which combination of concomitant medications might yield a positive response; short duration; inability to determine optimal dosage; and exclusion of patients with positional cervical myelopathy and untreated obstructive sleep apnea.
"In summary, a new treatment approach using a D3 [dopamine 3] receptor agonist offers hope to patients with fibromyalgia," the authors conclude. "Further investigation of this pramipexole treatment paradigm is warranted to determine its mechanism of action in patients with fibromyalgia, its long-term risks and benefits, and to confirm these findings in patients not taking concomitant medications."
Dr. Holman holds patents for the use of dopamine 2 and D3 receptor agonists in the treatment of fibromyalgia.
Arthritis Rheum. 2005;52:2495-2505
