title: Effect of rasagiline as adjunct therapy to levodopa on severity of OFF in Parkinson's disease.
abstract: BACKGROUND
  The LARGO study demonstrated that rasagiline 1 mg/day as adjunct to levodopa significantly reduces OFF time to the same magnitude as adjunct entacapone. This substudy of LARGO aimed to assess the effect of rasagiline and entacapone on the motor symptoms of PD during the practically defined OFF state.
  
  
  METHODS
  LARGO was a randomized, double-blind, multicenter trial that assessed the efficacy and safety of rasagiline (1 mg/day), entacapone (200 mg with each levodopa dose), and placebo in 687 levodopa-treated PD patients with motor fluctuations. A substudy of LARGO measured UPDRS motor scores in the practically defined OFF state in 32 rasagiline, 36 entacapone, and 37 placebo patients.
  
  
  RESULTS
  Treatment with rasagiline produced a significant improvement over placebo of 5.64 units in UPDRS motor OFF score (P = 0.013 vs. placebo). By contrast, the effect of adjunct entacapone was not significant (P = 0.14 vs. placebo). Whereas rasagiline also showed a trend in reducing the UPDRS-ADL OFF score (P = 0.058 vs. placebo), no such trend was noted for entacapone (P = 0.26 vs. placebo). Retrospective analysis, using the Bonferroni correction, of UPDRS motor subdomains further revealed that rasagiline, but not entacapone, significantly improved bradykinesia (P < 0.001) and showed trends for improvements in facial expression, speech, and axial impairment during OFF time.
  
  
  CONCLUSIONS
  This study provides the first objectively measured evidence that adjunct rasagiline 1 mg/day is effective in reducing the severity of motor symptoms in the OFF state. This suggests a continuous effect of rasagiline 1 mg/day throughout the day and night and is consistent with its extended duration of therapeutic action.
authors: Institute of Neurology, IRCCS San Raffaele, Pisana, Rome, Italy. fabrizio.stocchi@sanraffaele.it
authors: F
authors: F
authors: Stocchi
authors: J M
authors: JM
authors: Rabey
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002396:Catechols / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004401:Dysarthria / Q000188:drug therapy / Q000209:etiology; D005149:Facial Expression; D005260:Female; D006801:Humans; D018476:Hypokinesia / Q000188:drug therapy / Q000209:etiology; D007189:Indans / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects; D009127:Muscle Rigidity / Q000188:drug therapy / Q000209:etiology; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index; D014202:Tremor / Q000188:drug therapy / Q000209:etiology
chemical_list: D000978:Antiparkinson Agents; D002396:Catechols; D007189:Indans; D008996:Monoamine Oxidase Inhibitors; D009570:Nitriles; C031967:rasagiline; D007980:Levodopa; C071192:entacapone