Table 10Overall strength of evidence for individual outcomes in placebo-controlled studies of alpha-2-delta ligands

OutcomeTreatmentsNumber of TrialsnSummary Statistics [95% CI]Risk of BiasDirectnessPrecisionConsistencyEvidence Rating
IRLS responders (≥50% score reduction) reduction)All trials vs. placebo3503RR 1.66 [1.33 to 2.09]LowDirectPreciseConsistentHigh
Gabapentin enacarbil1321RR 1.54 [1.18 to 2.01]LowDirectPreciseUnknownModerate
Pregabalin2182RR 2.03 [1.33 to 3.11]LowDirectPreciseConsistentHigh
IRLS total score: mean change fromAll trials vs. placebo3475WMD −4.26 [−5.75 to −2.77]LowDirectPreciseConsistentHigh
BaselineGabapentin enacarbil2*431WMD −4.18 [−5.76 to −2.60]LowDirectPreciseConsistentHigh
Pregabalin144WMD −4.90 [−9.41 to −0.39]LowDirectPreciseUnknownModerate
Clinical global impressions: responders (much improved)All trials vs. placebo3662RR 1.60 [1.21 to 2.10]LowDirectPreciseConsistentHigh
Gabapentin enacarbil2**538RR 1.80 [1.51 to 2.14]LowDirectPreciseConsistentHigh
Pregabalin1124RR 1.14 [0.80 to 1.64]LowDirectImpreciseUnknownLow
RLS quality of lifeAll trials vs. placebo2263SMD 0.27 [−0.17 to 0.70]LowDirectImpreciseInconsistentLow
Gabapentin enacarbil1220SMD 0.42 [0.16 to 0.69]LowDirectPreciseUnknownModerate
Pregabalin143SMD −0.05 [−0.65 to 0.55] (300 mg dose)LowDirectImpreciseUnknownLow
Self-rated sleep MOS-sleep adequacyGabapentin enacarbil2431SMD 0.53 [0.33 to 0.72]LowDirectPreciseConsistentHigh
Any study withdrawalAll trials vs. placebo5936RR 0.71 [0.52 to 0.99]LowDirectPreciseConsistentHigh
Gabapentin enacarbil3741RR 0.70 [0.49 to 1.00]LowDirectPreciseConsistentHigh
Pregabalin2195RR 0.79 [0.37 to 1.68]LowDirectImpreciseInconsistentLow
Patients with ≥1 adverse eventAll trials vs. placebo5933RR 1.17 [0.1.00 to 1.36]LowDirectImpreciseConsistentModerate
Gabapentin enacarbil3738RR 1.09 [0.1.00 to 1.19]LowDirectPreciseConsistentHigh
Pregabalin2195RR 1.67 [0.74 to 3.80]LowDirectImpreciseConsistentModerate

CI = confidence interval; IRLS = International Restless Legs Study Group; MD = main difference; MOS = medical outcome scale; RLS = restless legs syndrome; RR = risk ratio; SMD = standardized mean difference; WMD = weighted mean difference

*

An additional crossover trial (Winkleman 2011) also reported significant improvement versus placebo (MD in improvement from baseline was −6.57 [95% CI −8.58 to −4.57].

**

An additional crossover trial (Winkleman 2011) also reported significant improvement versus placebo (Gabapentin enacarbil 74% much improved or very much improved versus 36% for placebo).

Fixed-dose trial (5 doses, 50–450 mg), range of SMDs from −0.05 to −0.43. No dose was significantly superior to placebo.

From: Results

Cover of Treatment for Restless Legs Syndrome
Treatment for Restless Legs Syndrome [Internet].
Comparative Effectiveness Reviews, No. 86.
Wilt TJ, MacDonald R, Ouellette J, et al.

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