Meta-analysis on the effectiveness of Gabapentin encarbil in lowering severity of primary restless legs syndrome

Background:  Restless legs syndrome (RLS) is a neurologic disorder characterized by unpleasant sensations and uncontrollable urge to move the limbs. Dopaminergic agents are considered as first-line therapy; however, these agents are associated with risk of augmentation. Gabapentin enacarbil (GEn) has been considered as a treatment candidate for RLS. Most phase II and III clinical trials for GEn involve Caucasian subjects. In 2013, a study was conducted by Inoue et al. among Japanese subjects to establish the effect of GEn among Asians with RLS. To date, no study has included this in a meta-analysis.

Objective: To obtain a definite conclusion in available phase III clinical RCTs on the effectiveness of GEn compared to placebo for the treatment of Primary RLS.

Methods: Mean decrease from baseline in the International Restless Legs Syndrome Total Score (IRLS) from each study was recorded. The mean difference at 95% confidence interval was calculated using Review Manager 5.2. Proportion of responders to both treatment and placebo as assessed using the Clinical Global Impression Scale were also recorded. A random effects model was used to account for possible sources of heterogeneity.

Results: GEn in 600 mg, 900 mg and 1,200 mg doses were effective over placebo in lowering severity of RLS, with the 1,200 mg dose having the highest decrease on IRLS scores compared to baseline.

Conclusion: Several randomized, placebo-controlled studies have demonstrated that GEn is an effective alternative to first line therapy to RLS. The results of this meta-analysis confirmed that all dose interventions were effective compared to placebo in lowering severity of RLS as evidenced by significant improvement in IRLS scores compared to baseline. The most significant improvement was seen in the 1,200 mg dose of GEn.