Objective To assess the efficacy and safety of gabapentin for restless legs syndrome (RLS). Methods Such databases as PubMed, EMbase, CENTRAL and CBM were searched for collecting the randomized controlled trials (RCTs) on the efficacy and/or tolerability of gabapentin for restless legs syndrome. Methodological quality of the trials was evaluated using the Cochrane risk-of-bias criteria, and meta-analysis was carried out using RevMan 5.1. Results Seven RCTs involving 1 163 patients which met the criteria were included, of which 4 were placebo parallel controlled trials and 3 were placebo cross-over trials. The outcomes of meta-analysis suggested that a) As to the change of RLS severity based on IRLSSG score, gabapentin was superior to placebo in alleviating the severity of RLS (MD= –3.24, 95%CI –4.40 to –2.09, Plt;0.000 01); b) As to the response rate based on investigator-rated CGI-I scale, it was higher in the gabapentin group (77%) compared with that in the placebo group (50%) (RR=1.81, 95%CI 1.54 to 2.11, Plt;0.000 01); c) As to quality of sleep, gabapentin was superior to placebo in reducing sleep disturbance (MD= –11.31, 95%CI –14.46 to –8.16), assuring quality of sleep (MD= 0.27, 95%CI 0.10 to 0.44) and alleviating daytime somnolence (MD= –3.96, 95%CI –6.42 to –1.50); and d) As to the RLS pain score, gabapentin was better in relieving pain compared with placebo (MD= –0.97, 95%CI –1.47 to –0.47). In addition, main side effects were somnolence (3.1% to 26.5%) and dizziness (2.1% to 19.5%), and there was a significant difference between two groups. Conclusion Gabapentin can effectively alleviate RLS patients’ condition, improve quality of sleep, relieve pain and show good tolerability.
Objective To systematically review the efficacy and safety of non-ergoline dopamine agonists (pramipexole, ropinirole, and rotigotine) and α2δ ligands (pregabalin and gabapentin-enacarbil) in the treatment of restless legs syndrome (RLS). Methods The PubMed, EMbase, The Cochrane Library, CBM, WanFang Data, and CNKI databases were electronically searched for randomized controlled trials (RCTs) assessing different medications for RLS from 2000 to 2021. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. The network meta-analysis was then performed using Stata 16.0 software and R 4.1.0 software. Results A total of 36 RCTs involving 7 666 patients were included. The results of the network meta-analysis showed that gabapentin-enacarbil decreased IRLS scores to the greatest extent among all drugs (MD=−6.42, 95%CI −8.8 to −4.16), was superior to pramipexole (MD=−3.27, 95%CI −6.54 to −0.15), and was associated with the highest CGI-I response rates (RR=1.73, 95%CI 1.52 to 2.00). In terms of tolerance and safety, patients receiving rotigotine presented an increased incidence of withdrawal due to adverse events. Ropinirole had the highest incidence of nausea. Headache was most common side effect in rotigotine, while the incidences of somnolence and dizziness were higher in gabapentin-enacarbil than other treatments. Conclusion Current evidence suggests that gabapentin-enacarbil may be the best treatment for RLS. Rotigotine is associated with the worst tolerance. For safety, nausea is most common in ropinirole, headache is most common for rotigotine, and patients receiving gabapentin-enacarbil show increased incidences of somnolence and dizziness.