Trial reportCNS drugs2025
Subclinical Augmentation in Relation to Previous Dopaminergic Treatment in Patients with Restless Legs Syndrome: A Post Hoc Analysis of Two Randomized, Placebo-Controlled, Crossover Trials.
Trial report in CNS drugs, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesAugmentation, a long-term complication of dopamine agonist treatment for restless legs syndrome (RLS), is preceded by a gradual loss of response. We investigated whether prior long-term dopaminergic treatment affects current and future responses to dopaminergic and non-dopaminergic drugs, which would suggest broader changes in RLS pathophysiology.
methodsWe retrospectively analysed two previously published, double-blind, randomized, crossover, placebo-controlled studies with the adenosine transport inhibitor dipyridamole and the orexin receptor antagonist suvorexant. Post hoc analyses compared responses between dopaminergic (DA)-naïve and dopaminergic (DA)-treated patients with RLS. None of these patients met the diagnostic criteria for augmentation. After a 2-week washout, patients received active treatment (10-20 mg suvorexant or 200-300 mg dipyridamole) or placebo for 2 weeks, followed by crossover. Efficacy was assessed using the International RLS Rating Scale (IRLS), Clinical Global Impressions-Severity scale (CGI-S), multiple suggested immobilization test (m-SIT), periodic leg movements of sleep (PLMS) and other polysomnographic measures.
resultsA total of 28 patients participated in the dipyridamole study (DA-pretreated, n = 10; DA-naïve group, n = 18), and 40 participated in the suvorexant study (DA-pretreated, n = 9; DA-naïve group, n = 31). Compared with DA-naïve patients, DA-pretreated patients responded significantly worse to both treatments on the basis of the IRLS, CGI-S, m-SIT, PLMS indices. There were no differences in sleep parameters.
conclusionsOur results suggest that previous long-term dopaminergic treatment, even before clinical augmentation is reached, induces pathophysiological changes in RLS that impair future responses to both dopaminergic and non-dopaminergic therapies. Our findings confirm previous results with gabapentin enacarbil and suggest that these changes develop well before clinical augmentation appears. Pathophysiological implications for the understanding of dopaminergic augmentation are discussed. Our results support the American Academy of Sleep Medicine (AASM) recommendation against using dopamine agonists as the initial choice for RLS treatment.
Indexed as
Identifiers
40467956What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.