| July 28, 2005 — 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:placebo) 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
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