The Efficacy and Safety of Pharmacological Treatments for Restless Legs Syndrome: Systemic Review and Network Meta-Analysis

Abstract

Although various drugs are currently used for restless legs syndrome (RLS) in clinic, selecting appropriate drugs for patients is difficult. This network meta-analysis (NMA) aimed to compare the efficacy and safety of different drugs. After literature searching and screening, 46 trials, including 10,674 participants are included in this NMA. The pooled results showed that, compared with placebo, only levodopa is inefficient to relieve symptoms of RLS. Cabergoline decreases IRLS scores to the greatest extent among all drugs (MD −11.98, 95% CI −16.19 to −7.78). Additionally, pramipexole is superior to ropinirole in alleviating symptoms of RLS (MD −2.52, 95% CI −4.69 to −0.35). Moreover, iron supplement alleviates RLS symptoms significantly compared with placebo in patient with iron deficiency (MD −5.15, 95% CI −8.99 to −1.31), but not for RLS patients with normal serum ferritin level (MD −2.22, 95% CI −6.99 to 2.56). For primary RLS, these drugs are also effective, while there is insufficient data to analyze drug efficacy in secondary RLS. We analyzed risk of common adverse effects of drugs including nausea, somnolence, fatigue, headache and nasopharyngitis. Alpha-2-delta ligands and DAs are favorable choices for both primary and secondary RLS because of their significant efficacy and good tolerability. Iron supplement can significantly alleviate symptoms of RLS patients with iron deficiency than placebo. We recommend gabapentin, gabapentin enacarbil, and pregabalin for clinicians for first consideration mainly because that they rarely cause augmentation. Oxycodone-naloxone could be considered in patients with severe or very severe RLS who failed in treatment with above drugs.

Antiseizure Drugs and Movement Disorders

“…Larger trials with a similar design confirmed the efficacy of gabapentin on RLS [44]. A systematic review and meta-analysis recommend gabapentin as the first option for RLS mainly because it rarely causes augmentation [45].…”

“…Similarly, improvements were observed in terms of the CGI Scale, RLS-6 scale, and the Medical Outcomes Study Sleep Scale (all p < 0.01) [61]. Pregabalin is one of the main recommended drugs for RLS because in addition to the significant efficacy and good tolerability, it rarely causes augmentation according to a systematic review [45].…”

Brain iron acquisition: An overview of homeostatic regulation and disease dysregulation

“…RLS affects approximately 9.8% of the population, with women accounting for roughly two-thirds of all RLS patients (Berger et al, 2002). The exact pathological mechanisms at play are poorly understood; however, the improvement of RLS symptoms in response to iron supplementation and DA agonists points to dysregulation in these two processes (Zhou et al, 2021).…”

Exploration of restless legs syndrome under the new concept: A review

“…[ 65 ] This extended duration of action and sustained release of dopamine into the blood may minimize dopamine fluctuations at the receptor and may be associated with a low propensity to evolve into potentiation syndrome. [ 65 ] The dose of rotigotine can be started at a patch strength of 1.0 mg and increased weekly to a maximum daily dose of 2.0 or 3.0 mg. [ 66 ] Clinical trials of rotigotine have shown that a further dose increase to 4.0 mg per day could be considered, but this high dose may carry a greater risk of enhancement. [ 67 ] Rotigotine, as a transdermal patch, may cause skin reactions, such as excessive itching or redness of the skin at the application site.…”