February 26, 2014

DynaMed EBM Journal Volume 9, Issue 9

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Physicians: .25 AMA PRA Category ICreditsTM

Family Physicians: .25 Prescribed credits

Nurse Practitioners: .25 Contact hours

Release Date: February 26, 2014

Expiration Date: February 26, 2015

Estimated Completion Time: 15 minutes

There is no fee for this activity.

To Receive Credit

In order to receive your certificate of participation, you should read the information about this activity, including the disclosure statements, review the entire activity, take the post-test, and complete the evaluation form. You may then follow the directions to print your certificate of participation. To begin, click the CME icon at the end of the article.

Program Overview

Learning Objectives

Upon successful completion of this educational program, the reader should be able to:
1. Discuss the significance of this article as it relates to your clinical practice.
2. Be able to apply this knowledge to your patient's diagnosis, treatment and management.

Faculty Information

Alan Ehrlich, MD - Assistant Clinical Professor in Family Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; Senior Deputy Editor, DynaMed, Ipswich, Massachusetts, USA

Michael Fleming, MD, FAAFP - Assistant Clinical Professor of Family Medicine and Comprehensive Care, LSU Health Science Center School of Medicine, Shreveport, Louisiana, USA; Assistant Clinical Professor of Family Medicine, Department of Family and Community Medicine, Tulane University Medical School, New Orleans, Louisiana, USA; Chief Medical Officer, Amedisys, Inc. & Antidote Education Company


Dr. Ehrlich, Dr. Fleming, DynaMed Editorial Team members, and the staff of Antidote Education Company have disclosed that they have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity.

No commercial support has been received for this activity.

Accreditation Statements

ACCME: This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Antidote EducationCompany and EBSCO Publishing. Antidote is accredited by the ACCME to provide continuing medical education for physicians. Antidote Education Company designates this enduring activity for a maximum of 0.25 AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

AAFP: Enduring Material activity, DynaMed EBM Focus, has been reviewed and is acceptable for up to 13 Prescribed credits by the American Academy of Family Physicians. AAFP certification begins March 7, 2012. Term of approval is for one year from this date with the option of yearly renewal. Each EBM Focus is worth .25 Prescribed credits. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AANP: This program is approved for 0.25 contact hour of continuing education by the American Academy of Nurse Practitioners.

Program ID: 1304159Q


Last week 593 journal articles were evaluated via DynaMed's Systematic Literature Surveillance and summaries of 245 articles were added to DynaMed content.

Based on criteria for selecting "articles most likely to change clinical practice," one article was selected by the DynaMed Editorial Team.

In Adults with Restless Legs Syndrome, Pregabalin Has Greater Efficacy With Less Iatrogenic Worsening of Symptoms Than Higher Doses of Pramipexole
Reference: N Engl J Med 2014 Feb 13;370(7):621 (level 2 [mid-level] evidence)

Dopamine agonists are currently the standard first-line treatment for patients with daily symptoms of restless legs syndrome (RLS). A Cochrane review has provided high-quality evidence that dopamine agonists reduce symptoms of RLS (Cochrane Database Syst Rev 2011 Mar 16;(3):CD006009), and the American Academy of Sleep Medicine guidelines currently recommend treatment of these patients with either pramipexole or ropinirole (Sleep 2012 Aug 1;35(8):1039 full-text). However, dopamine agonists may result in worsening of symptoms months after treatment, an effect referred to as augmentation. The anticonvulsant pregabalin is an alternative treatment that was previously found to be beneficial for RLS in a small randomized trial (Neurology 2010 Jun 8;74(23):1897). Now, a randomized trial compares pregabalin to placebo and to 2 separate doses of pramipexole in adults with RLS.

A total of 731 adults with moderate-to-severe RLS symptoms for ≥ 6 months were randomized to 1 of 4 oral treatments for 12 weeks: pregabalin 300 mg/day, pramipexole 0.25 mg/day, pramipexole 0.5 mg/day, or placebo. Patients initially randomized to placebo were re-randomized to active treatment with pregabalin, pramipexole 0.25 mg/day, or pramipexole 0.5 mg/day for an additional 40 weeks. RLS symptoms were assessed with the International RLS Study Group Rating Scale (range 0-40, with higher scores indicating greater symptom severity, and the minimal clinical important difference defined as 3 points). At baseline, all patients had an RLS symptom score ≥ 15 points (mean score 22.3 points). The 12-week change in RLS symptom score was a primary analysis, and included 696 patients (95% of those randomized) who received study treatment and had at least 1 post-baseline assessment.

The mean reduction from baseline in RLS symptom score at 12 weeks was 11.4 points with pregabalin (p < 0.001 vs. placebo), 7.8 points with pramipexole 0.25 mg/day (not significant vs. placebo), 10.1 points with pramipexole 0.5 mg/day (p < 0.001 vs. placebo), and 6.9 points with placebo. Pregabalin was associated with lower RLS symptom scores than pramipexole 0.25 or 0.5 mg/day at 52 weeks (p < 0.001 for each). The proportion of patients with a clinical global impression of “much improved” or “very much improved” symptoms at 12 weeks was 71.4% with pregabalin (p < 0.001 vs. placebo, NNT 4), 51.2% with pramipexole 0.25 mg/day (not significant vs. placebo), 62.7% with pramipexole 0.5 mg/day (p = 0.002 vs. placebo, NNT 7), and 46.8% with placebo. The augmentation rates at the end of trial were 2.1% with pregabalin (p < 0.001 vs. pramipexole 0.5 mg, NNT 18, and p = 0.08 vs. pramipexole 0.25 mg), 5.3% with pramipexole 0.25 mg, and 7.7% with pramipexole 0.5 mg.

Although dopamine agonists have demonstrated efficacy in reducing symptoms of restless legs syndrome, the augmentation of symptoms after treatment initiation is now recognized as an important limitation. A recent cohort study found that augmentation rates were consistent after the first year and persisted for up to 10 years, with only 58% of patients on pramipexole continuing with treatment after 5 years (Sleep Med 2011 May;12(5):440). This new randomized trial shows that pregabalin is at least as effective as pramipexole, with a significantly lower rate of augmentation. However, it is important to keep in mind that pregabalin has not been studied extensively in this patient population, and long-term safety and efficacy data are not yet available.

For more information see the Restless legs syndrome (RLS) topic in Dynamed.

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