Pregabalin Versus Pramipexole: Effects on Sleep Disturbance in Restless Legs Syndrome

Garcı́a-Borreguero, Diego; Patrick, Jeffrey; Dubrava, Sarah; Becker, Philip M.; Lankford, Alan; Chen, Crystal; Miceli, J.; Knapp, Lloyd; Allen, Richard P.

doi:10.5665/sleep.3558

Cited by 78 publications

(64 citation statements)

References 38 publications

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“…Because results of this Class I study were not statistically significant and CIs included both potentially clinically important and unimportant effects, there is insufficient evidence to support or refute the effect of gabapentin enacarbil on the PLMI. It is likely that gabapentin enacarbil improves RLS-specific QoL (1 Class I study 37 ) and mood (1 Class I study 36 24,25,40 ; there is insufficient evidence to support or refute doses of 50-100 mg/d because analyses did not reach statistical significance but CIs 1 of which had insufficient precision at many doses). Pregabalin 300 mg possibly improves RLS-related QoL (1 Class II study 25 ; 1 Class I study 39 reported no difference but did not provide data to assess).…”

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confidence: 99%

“…There is insufficient evidence to support or refute the superiority of pregabalin over pramipexole for treating IRLS symptoms (metaanalysis of 2 Class II studies 24,25 where the mean difference point estimate is not compared with pramipexole). Pregabalin likely improves subjective sleep outcomes more than pramipexole (2 Class II studies 24,25 ).…”

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confidence: 99%

“…It is highly likely that pramipexole improves RLS symptoms as measured by the IRLS (3 Class I 16-18 and 6 Class II studies [19][20][21][22][23][24] over varying timeframes). It is likely that pramipexole improves PLMS (3 Class II studies 20,22,25 ) and subjective sleep measures (1 Class I 17 and 3 Class II studies, 19,21,23 with an additional Class II study lacking the precision to exclude an important effect 24 ). There is insufficient evidence to support or refute an effect of pramipexole on other polysomnographic measures (e.g., sleep latency, sleep efficiency, WASO, or TST) on the basis of results with varied statistical significance and clinical importance across 3 Class II studies 20,22,25 with sometimes limited statistical reporting.…”

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confidence: 99%

“…It is likely that pramipexole improves PLMS (3 Class II studies 20,22,25 ) and subjective sleep measures (1 Class I 17 and 3 Class II studies, 19,21,23 with an additional Class II study lacking the precision to exclude an important effect 24 ). There is insufficient evidence to support or refute an effect of pramipexole on other polysomnographic measures (e.g., sleep latency, sleep efficiency, WASO, or TST) on the basis of results with varied statistical significance and clinical importance across 3 Class II studies 20,22,25 with sometimes limited statistical reporting. It is likely that pramipexole improves RLS-specific QoL at 12 weeks (1 Class I 16 and 3 Class II studies, 19,23,24 with one of the Class II studies showing limited improvement 24 ).…”

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confidence: 99%

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Practice guideline summary: Treatment of restless legs syndrome in adults

et al. 2016

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Practice guideline summary: Treatment of restless legs syndrome in adults

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“…Integration of newly reported indices into HSMD have the potential to provide valuable clinical information on the various PLM phenotypes, [7][8][9][10] genotypes [11,12] and efficacy of pharmacological interventions [13].…”

Section: Why Are Hsmd the Tools To Assess Plms?mentioning

confidence: 99%

Home Sleep-Monitoring Devices: Bridging the Periodic Limb Movement in Sleep Information Gap

Schramm¹

2017

J Sleep Disord Ther

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The prevalence of periodic limb movement in sleep (PLMS) in patients with Restless Legs Syndrome is estimated between 80 to 90%, >34% of the population over 60 years of age and 36% of healthy subjects were found to have a PLMS index >5 event per hour of sleep. PLMS can be associated with sleep breathing disorders, insomnia, narcolepsy, and REM Behavior disorder. Its prevalence in the general population is unknown. Home sleepmonitoring devices (HSMD) could be used to derive some consensus on the clinical and non-clinical characteristics of PLMS. There is need to derive age-adjusted normative values for PLMS, assess their clinical significance when presenting as comorbidities, phenotyping the genetic variants and tracking the pathophysiology along a continuum to determine signs and symptom changes from pre-clinical to clinical relevance. This article provides information on why and how HSMD is the logical approach in bridging the clinically relevant information gap associated with PLMS. It discusses future directions to be taken in utilizing HSMD to objectively measure PLMS and determine their effect on sleep quality.

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Targeting hypersensitive corticostriatal terminals in restless legs syndrome

Yepes

Guitart

Rea

et al. 2017

Annals of Neurology

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Objective The first aim was to demonstrate a previously hypothesized increased sensitivity of corticostriatal glutamatergic terminals in the rodent with brain iron deficiency (BID), a pathogenetic model of Restless Legs Syndrome (RLS). The second aim was to determine if these putative hypersensitive terminals could constitute a significant target for drugs effective in RLS, including dopamine agonists (pramipexole and ropinirole) and α2δ ligands (gabapentin). Methods A recently introduced in vivo optogenetic-microdialysis approach was used, which allows the measurement of the extracellular concentration of glutamate upon local light-induced stimulation of corticostriatal glutamatergic terminals. The method also allows to analyze the effect of local perfusion of compounds within the same area being sampled for glutamate. Results BID rats showed hypersensitivity of corticostriatal glutamatergic terminals (lower frequency of optogenetic stimulation to induce glutamate release). Both hypersensitive and control glutamatergic terminals were significant targets for locally perfused pramipexole, ropinirole and gabapentin, which significantly counteracted optogenetically-induced glutamate release. The use of selective antagonists demonstrated the involvement of dopamine D4 and D2 receptor subtypes on the effects of pramipexole. Interpretation Hypersensitivity of corticostriatal glutamatergic terminals can constitute a main pathogenetic mechanism of RLS symptoms. Selective D4 receptor agonists, by specifically targeting these terminals, should provide a new efficient treatment with less secondary effects.

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Pregabalin Versus Pramipexole: Effects on Sleep Disturbance in Restless Legs Syndrome

Abstract: ClinicalTrials.gov identifier, NCT00991276; http://clinicaltrials.gov/show/NCT00991276.

Cited by 78 publications

References 38 publications

Practice guideline summary: Treatment of restless legs syndrome in adults

Practice guideline summary: Treatment of restless legs syndrome in adults

Home Sleep-Monitoring Devices: Bridging the Periodic Limb Movement in Sleep Information Gap

Targeting hypersensitive corticostriatal terminals in restless legs syndrome

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