PMID- 30772697
OWN - NLM
STAT- MEDLINE
DCOM- 20200429
LR  - 20200429
IS  - 1878-5506 (Electronic)
IS  - 1389-9457 (Linking)
VI  - 55
DP  - 2019 Mar
TI  - Reduced response to gabapentin enacarbil in restless legs syndrome following 
      long-term dopaminergic treatment.
PG  - 74-80
LID - S1389-9457(18)30509-4 [pii]
LID - 10.1016/j.sleep.2018.11.025 [doi]
AB  - OBJECTIVES: To determine whether long-term treatment with dopaminergic agents 
      (DAs) might dampen the response to a non-dopaminergic agent, such as gabapentin 
      enacarbil. METHODS: We performed a two-week randomized, double-blind, crossover, 
      and placebo-controlled study in a single, referral center in dopamine 
      treatment-naive patients and non-augmented patients continuously treated with 
      dopaminergics for the last five consecutive years. Following washout from any 
      previous CNS-active drugs, patients were randomized into one of two groups for 
      two consecutive two-week treatment periods with gabapentin enacarbil (GBPen) and 
      placebo. Treatment was administered at 7 PM at a fixed dose of 600 mg/day. RLS 
      severity was measured weekly using the International RLS Scale (IRLS) and 
      Clinical Global Improvement (CGI). An M-SIT was also performed between 6 pm and 
      midnight at the end of each treatment condition. RESULTS: There were no 
      significant differences between groups in age, sex, duration of disease, ferritin 
      levels, RLS severity at baseline, or existing concomitant conditions. Both groups 
      improved more during treatment with GBPen than during placebo on the IRLS scale, 
      CGI and mSIT. However, improvements were greater in the DA-naive group than in 
      long-term treatment with DAs group on the IRLS (p < 0.05), CGI (p < 0.01), and 
      mSIT (p < 0.01). CONCLUSIONS: Previous long-term treatment with DAs reduces 
      future response to GBPen in RLS patients. Potential pathiophysiological 
      explanations are discussed. Our finding has strong implications for the initial 
      choice of treatment in RLS and supports the notion that initial treatment should 
      not be started with DAs. CLASSIFICATION OF EVIDENCE: The study provides class II 
      evidence supporting reduced effects of gabapentin enacarbil in RLS patients 
      previously exposed to long-term treatment with dopamine agonists.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Garcia-Borreguero, Diego
AU  - Garcia-Borreguero D
AD  - Sleep Research Institute, Madrid, Spain. Electronic address: dgb@iis.es.
FAU - Cano-Pumarega, Irene
AU  - Cano-Pumarega I
AD  - Sleep Research Institute, Madrid, Spain. Electronic address: 
      irene.cano@yahoo.com.
FAU - Garcia Malo, Celia
AU  - Garcia Malo C
AD  - Sleep Research Institute, Madrid, Spain. Electronic address: 
      celia.garcia.malo@gmail.com.
FAU - Cruz Velarde, Jose Antonio
AU  - Cruz Velarde JA
AD  - Neuronae, Villaviciosa de Odon, Spain. Electronic address: 
      jacruzvelarde@gmail.com.
FAU - Granizo, Juan Jose
AU  - Granizo JJ
AD  - Sleep Research Institute, Madrid, Spain. Electronic address: 
      jjgranizo@granadatos.com.
FAU - Wanner, Vivian
AU  - Wanner V
AD  - European Sleep Institute, Santiago, Chile. Electronic address: 
      vwanner@institutoeuropeodelsueno.cl.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20181226
PL  - Netherlands
TA  - Sleep Med
JT  - Sleep medicine
JID - 100898759
RN  - 0 (1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic 
      acid)
RN  - 0 (Carbamates)
RN  - 0 (Dopamine Agents)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
SB  - IM
MH  - Aged
MH  - Carbamates/*administration & dosage
MH  - Cross-Over Studies
MH  - Dopamine Agents/*administration & dosage
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Restless Legs Syndrome/*diagnosis/*drug therapy/physiopathology
MH  - Time Factors
MH  - Treatment Outcome
MH  - gamma-Aminobutyric Acid/administration & dosage/*analogs & derivatives
OTO - NOTNLM
OT  - Alpha-2 delta ligands
OT  - Augmentation
OT  - Dopamine agonists
OT  - Restless legs syndrome
OT  - Treatment failure
OT  - Willis Ekbom disease
EDAT- 2019/02/18 06:00
MHDA- 2020/04/30 06:00
CRDT- 2019/02/18 06:00
PHST- 2018/08/07 00:00 [received]
PHST- 2018/11/04 00:00 [revised]
PHST- 2018/11/26 00:00 [accepted]
PHST- 2019/02/18 06:00 [pubmed]
PHST- 2020/04/30 06:00 [medline]
PHST- 2019/02/18 06:00 [entrez]
AID - S1389-9457(18)30509-4 [pii]
AID - 10.1016/j.sleep.2018.11.025 [doi]
PST - ppublish
SO  - Sleep Med. 2019 Mar;55:74-80. doi: 10.1016/j.sleep.2018.11.025. Epub 2018 Dec 26.