Table DFuture research recommendations

Topical IssuesSpecific Research GapsRecommendations
Limited evidence base
  • Evidence base consists almost exclusively of pharmacologic treatments, and dopamine agonists in particular.
  • Many classes of drugs used in clinical practice such as opioids and sedative hypnotics have not been evaluated in clinical trials.
  • We found no evidence for effectiveness of therapies in specific subgroups such as children, older adults with multimorbidities, or individuals with secondary RLS.
Long-term durability of treatment benefits
  • Long-term durability of treatment benefits remains unknown.
  • High-quality, long-term, open-label extension studies from randomized trials that establish the time frame over which treatment benefits are sustained for different drugs and in specific group of patients.
Impact of patient characteristics on treatment outcomes
  • We found no studies that address how patient characteristics, such as disease duration and previous therapy, affect treatment outcomes.
  • Randomized trials that report effectiveness of treatments for subgroups of patients such as those with different disease duration, those new to treatment, and those for whom previous treatment failed.
  • Augmentation is a significant harm with dopaminergic therapy and can lead to treatment discontinuation; yet, little is known about patient characteristics that may lead to augmentation.
  • Long-term studies of augmentation with dopaminergic therapy. Potential study designs could include RCTs, prospective observational studies, and retrospective observational studies, including case-control studies..
  • Studies that evaluate specific patient characteristics such as iron status and disease severity that may make patients susceptible to augmentation with dopaminergic therapy.
Methodological IssuesFindingsResearch Needs
Outcome measures
  • It is not clear if the degree of benefit as established by symptom scale scores such as IRLS scale translate to meaningful improvement for patients.
  • The clinical relevance of objective measures of assessment such as polysomnography is not clear.
  • Establish minimum important differences in scale scores that translate to clinically significant improvement for individual patients.
  • Report outcomes such as proportions of patients with remission of symptoms (IRLS score=0), patient-reported sleep outcomes, and quality of life.
  • Establish clinical relevance of polysomnography and other objective outcomes (perform studies correlating polysomnography outcomes to clinically significant changes such as remission of symptoms).
Time frame for evaluation of treatments
  • Most clinical trials were of short duration (typically 12 weeks) yet RLS patients whose symptoms are severe confront a chronic, progressive disease that may require lifelong treatment.
  • Longer term (>6 months) studies to establish if treatment benefits are sustained over time and to ascertain long-term harms such as augmentation.
Severity of disease
  • Clinical trials include patients with moderate to very severe disease typically by specifying a cut-off in IRLS scale score (IRLS score>15).
  • Evaluate and report treatment effectiveness for RLS patients with different degrees of symptom severity. (e.g., categories of severity by IRLS scale scores: 1–10: mild; 11–20: moderate; 21–30: severe; 31–40: very severe).
Assessment of augmentation with dopaminergic therapy
  • Considerable variation in reported prevalence of augmentation by type of drug, time frame of evaluation, and method of assessment.
  • Assess augmentation with different dopaminergic drugs using standard criteria and methods of assessment.

IRLS = International Restless Legs Syndrome Study Group Rating Scale; RCT = randomized controlled trial; RLS = restless legs syndrome

From: Executive Summary

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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