Entacapone prolongs the reduction of PLM by levodopa/carbidopa in restless legs syndrome.
OBJECTIVE
Levodopa is effective in the treatment of restless legs syndrome (RLS). However, due to the short duration of action of conventional levodopa/decarboxylase inhibitor formulations, multiple dosing may be required in individual patients with persisting symptoms. We assessed whether a new levodopa formulation containing levodopa, carbidopa, and entacapone (LCE) improves levodopa action in RLS.


METHODS
Twenty-eight RLS patients with periodic limb movement (PLM) received single doses of Stalevo 50 (LCE50; 50/12.5/200 mg), Stalevo 100 (LCE100; 100/25/200 mg), Stalevo 150 (LCE150; 150/37.5/200 mg), Sinemet 100 (LC100; 100/25 mg), or placebo in a randomized, double-blind, crossover study with polysomnography. Periodic limb movements per hour (PLM/h) during total sleep time and PLM during total time in bed were the primary and secondary variables, respectively.


RESULTS
Mean PLM/h during total sleep time after Stalevo 50 (12.6/h, P < 0.05), LCE100, LCE150, and LC100 (6.4/h, 3.5/h and 9.5/h, respectively; P < 0.01) were significantly reduced compared with placebo (25.7/h). Improvement was also observed in PLM/h during total time in bed for all treatments (P < 0.01) and a significant dose response observed between LCE doses (P < 0.05). Compared with LC100, LCE100 and LCE150 reduced PLMs during the second half (P = 0.06 and P < 0.001, respectively) or during the last 3 early morning hours (hours 5-7 from the start of recording) of the night (P < 0.05 and P < 0.01, respectively). All formulations were well tolerated.


CONCLUSIONS
Single doses of LCE tablets decreased PLMs in a dose-related manner in RLS patients. Prolonged effects of levodopa on PLMs suggest that, compared with standard levodopa, this new levodopa formulation provides longer symptom control throughout the night in patients with previously untreated RLS.
Polo
Olli
O
Sleep Research Unit, Department of Physiology, University of Turku and Tampere University Hospital, Finland.
Ylä-Sahra
Riitta
R
Hirvonen
Kari
K
Karvinen
Johanna
J
Vahteristo
Mikko
M
Ellmén
Juha
J
D002230:Carbidopa / Q000627:therapeutic use*; D002396:Catechols / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D009068:Movement / Q000187:drug effects; D009570:Nitriles / Q000627:therapeutic use*; D017286:Polysomnography / Q000379:methods; D011446:Prospective Studies; D012148:Restless Legs Syndrome / Q000188:drug therapy* / Q000503:physiopathology*; D012720:Severity of Illness Index
D002396:Catechols; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D009570:Nitriles; C481098:Stalevo; D007980:Levodopa; C071192:entacapone; D002230:Carbidopa