Article Figures & Data
Figures
- Figure 1.
Flow diagram of trial identification, inclusion, and exclusion.
IRLS = International Restless Legs Syndrome Study Group Scale score; CGI-I = Clinical Global Impression-Improvement scale.
- Figure 2.
Nonergot dopamine agonist’s impact on response to clinical global impression-improvement scale (A) and International Restless Legs Syndrome Study Group Scale score (B).
CI=confidence interval.
Note: The squares represent individual studies and the size of the square represents the weight given to each study in the meta-analysis. Error bars represent 95% CIs. The diamond represents the combined results. The solid vertical line extending upwards from 0 (CGI) or 1 (IRLS) is the null value.
- Figure 3.
Subgroup and sensitivity analyses of nonergot dopamine agonists evaluating response to Clinical Global Impression-Improvement scale.
CI=confidence interval; DA = dopamine agonists; ITT = intention to treat; NEDA = nonergot dopamine agonist; RR = relative risk.
Note: The dashed vertical line represents the combined treatment effect for the original analysis.
- Figure 4.
Subgroup and sensitivity analyses of nonergot dopamine agonists evaluating mean change in International Restless Legs Syndrome Study Group scale.
CI=confidence interval; DA = dopamine agonists; ITT = intention to treat; NEDA = nonergot dopamine agonist; WMD = weighted mean difference.
Note: The dashed vertical line represents the combined treatment effect for the original analysis.
- Figure 5.
Random-effects meta-regression evaluating effect of NEDAs on mean change in IRLS (A) and CGI-I (B) over time.
NEDAs = nonergot dopamine agonists; IRLS = International Restless Legs Syndrome Study Group Scale; CGI-I = Clinical Global Impression-Improvement; RR=relative risk.
Note: The circles represent individual studies, and the area of the circle is proportional to the weight of each study. The dark line represents the regression equation as represented by the following equation: (A) weighted mean difference = −11.3545 + 0.6574 × study duration; (B) LnRR=0.5304–0.0219 × study duration.
Tables
Reference Design N Baseline IRLS Mean+SD Follow-up (weeks) Drug/Dose Adjusted Mean Difference IRLS Mean+SE Treatment CGI-I Responder Rate (%) Jadad Score CGI-I = Clinical Global Impression – Improvement scale; DB = double-blind; IRLS = International Restless Legs Syndrome Study Group scale; N/A=not available; P=prospective; PC=placebo control; R=randomized. Allen (2004)17 P, R, DB, PC 55 N/A 12 Ropinirole 0.25–4.0 mg/d –1.2±2.1 Ropinirole=17/32 (53) Placebo=17/33 (52) 3 Stiasny-Kolster (2004)18 P, R, DB, PC 63 25.0 ± 5.0 1 Rotigotine 1.125–4.5 mg/24 h N/A Rotigotine=34/49 (69) Placebo=6/14 (43) 4 Trenkwalder (2004)19 P, R, DB, PC 284 24.4 ± 5.8 12 Ropinirole 0.25–4.0 mg/d –3.0±1.1 Ropinirole=78/146 (53) Placebo=56/138 (41) 4 Walters (2004)20 P, R, DB, PC 267 23.6 ± 5.9 12 Ropinirole 0.25–4.0 mg/d –2.5±1.1 Ropinirole=78/131 (60) Placebo=53/135 (39) 5 Bogan (2006)21 P, R, DB, PC 381 22.0 ± 5.0 12 Ropinirole 0.25–4.0 mg/d –3.7±0.9 Ropinirole=137/187 (73) Placebo=109/193 (56) 5 Inoue (2006)22 P, R, DB, PC 41 N/A 6 Pramipexole 0.125–0.75 mg/d –11.5±3.0 Pramipexole=16/20 (80) Placebo=11/21 (52) 3 Partinen (2006)23 P, R, DB, PC 107 22.7 ± 4.1 3 Pramipexole 0.125–0.75 mg/d –9.2±1.7 Pramipexole=65/86 (76) Placebo=9/21 (43) 3 Winkelman (2006)24 P, R, DB, PC 339 23.4 ± 5.1 12 Pramipexole 0.25–0.75 mg/d –4.3±1.1 Pramipexole=183/254 (72) Placebo=44/85 (52) 4 Garcia-Borreguero (2007)25 P, R, DB. PC 270 25.4 8 Sumanirole 0.5–4.0 mg/d N/A Sumanirole=104/212 (49) Placebo=26/51 (51) 3 Oertel (2007)26 P, R, DB. PC 341 28.0 ± 6.3 6 Rotigotine 0.5–4 mg/24 h N/A Rotigotine=212/280 (76) Placebo=29/53 (55) 5 Oertel (2007)27 P, R, DB. PC 338 24.7 ± 5.2 6 Pramipexole 0.125–0.75 mg/d –6.6±1.1 Pramipexole=141/224 (63) Placebo=37/114 (32) 3 RRL10001328 P, R, DB, PC 359 26.0 ± 4.4 12 Ropinirole 0.5–6.0 mg/d –4.1±1.0 Ropinirole=124/175 (71) Placebo=92/184 (50) 4 ROP10189229 P, R, DB, PC 298 23.5 ± 6.2 12 Ropinirole 0.25–4.0 mg/d N/A Ropinirole=92/152 (61) Placebo=76/146 (52) 4 SKF10146830 P, R, DB, PC 54 26.6 ± 5.3 7 Ropinirole 0.25–4.0 mg/d –9.9±2.9 N/A 3 Group W/D due to ADEs RR (95% CI) Headache RR (95% CI) Nausea RR (95% CI) Dizziness RR (95% CI) Somnolence RR (95% CI) Fatigue RR (95% CI) ADEs=adverse drug events; CI=confidence interval; N/A = not available; RR = relative risk; W/D = withdrawal. a P<.05. Dopamine agonists 1.35 (1.00–1.81)a 1.20 (0.98–1.47) 3.25 (2.36–4.48)a 1.47 (1.02–2.13)a 1.94 (1.45–2.61)a 1.37 (1.01–1.86)a Pramipexole 1.15 (0.49–2.69) 0.99 (0.64–1.54) 2.68 (1.51–4.76)a 1.03 (0.51–2.07) 1.55 (0.75–3.20) 1.09 (0.64–1.85) Ropinirole 1.49 (1.06–2.10)a 1.21 (0.95–1.54) 3.95 (2.76–5.66)a 1.72 (1.13–2.62)a 2.03 (1.47–2.80)a 1.72 (1.18–2.68)a Rotigotine 0.46 (0.08–2.58) 1.34 (0.54–3.33) 0.82 (0.16–4.24) 0.58 (0.19–1.73) N/A 0.78 (0.32–1.92) Sumanirole 1.11 (0.06–19.45) 2.68 (1.01–7.11)a 4.77 (0.65–34.69) 4.53 (0.62–33.04) N/A N/A
The Article in Brief
Background People with restless legs syndrome experience unpleasant sensations in the legs and an uncontrollable urge to move to relieve these feelings. A type of drug called nonergot dopamine agonists (NEDAs) is often used to treat restless legs syndrome. This study examines existing research to evaluate the effectiveness of NEDAs in treating restless legs syndrome, the risk of side effects, and the influence of side effects on whether patients continue to take the drugs.
What This Study Found Patients taking NEDAs show significant improvement in symptoms and severity of restless legs syndrome, especially in the early stages of treatment. Many patients discontinue use of the drugs, however, because of side effects, including nausea, dizziness, sleepiness, and fatigue.
Implications
- It is possible that individual NEDA drugs might differ from one another in terms of effectiveness and safety. Future research should directly compare NEDAs with each other in patients with restless legs syndrome and examine the drugs� long-term effects.
