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Use of nonergot dopamine agonists (NEDAs) in patients with moderate
to severe restless legs syndrome results in significant reductions in
the severity of symptoms, but a significant proportion of patients will
discontinue use as a result of adverse events, according to the results
of a meta-analysis reported in the May-June issue of the Annals of Family Medicine.
"Dopamine
agonists, particularly nonergot dopamine agonists (NEDAs), have become
the mainstay of therapy for patients with daily symptoms of restless
legs syndrome," write William L. Baker, PharmD, from the University of
Connecticut School of Pharmacy in Storrs, and colleagues. "NEDAs are
generally preferred to ergot dopamine agonists (eg, pergolide,
cabergoline), which have been associated with clinically important
heart valve damage and resultant regurgitation. Numerous clinical
trials have evaluated the efficacy and safety of NEDAs for restless
legs syndrome with conflicting results."
The reviewers performed
a systematic search of the literature through July 2007 for studies of
NEDA (pramipexole, ropinirole, rotigotine, and sumanirole) treatment of
restless legs syndrome. The main endpoints analyzed were the percentage
of responders to medication, as determined by the Clinical Global
Impression-Improvement (CGI-I) scale and the adjusted mean change in
the International Restless Legs Syndrome Study Group Scale (IRLS) score
from baseline vs placebo. A meta-regression analysis determined the
effect of study duration on the main efficacy endpoints, and safety
endpoints were also assessed.
The meta-analysis included 14
trials that enrolled a total of 3197 subjects. NEDA use was associated
with greater response rates on the CGI-I scale (relative risk [RR],
1.36; 95% confidence interval [CI], 1.24 - 1.49; P <.001) and greater reductions from baseline in IRLS scores (weighted mean difference [WMD], –4.93; 95% CI, –6.42 to –3.43; P <.001) vs placebo.
The
duration of the studies was inversely related with the reduction in
IRLS score, based on meta-regression analysis. There was a significant
risk for adverse events associated with treatment with NEDAs, including
nausea, dizziness, somnolence, and fatigue (RR, 1.35; 95% CI, 1.00 -
1.81).
"Use of NEDAs in patients with moderate-to-severe restless
legs syndrome results in significant reductions in symptom severity,
but a significant portion of patients will discontinue their use as a
result of adverse events," the study authors write.
Limitations
of the meta-analysis were inclusion of unpublished trials available
only online, hindering critical evaluation of their methods and
results; potential publication bias; and limitations of symptom score
and disease severity scales.
"There may be qualitative
differences in both efficacy and safety between agents, although no
definitive comparisons can be made," the reviewers conclude.
"Meta-regression analysis suggests that these agents are most
beneficial in the early stages of treatment. Future studies should be
conducted to compare directly the efficacy of individual NEDAs against
each other in patients with restless legs syndrome, as well as include
a longer period follow-up period to assess the long-term effects of
these agents."
The study authors have disclosed no relevant financial relationships.
Ann Fam Med. 2008;6:253-262.
http://www.medscape.com/viewarticle/574322?sssdmh=dm1.351312&src=nldne
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