title: Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson's disease (PD MED): a large, open-label, pragmatic randomised trial.
abstract: BACKGROUND
  Whether initial treatment for Parkinson's disease should consist of levodopa, dopamine agonists, or monoamine oxidase type B inhibitors (MAOBI) is uncertain. We aimed to establish which of these three classes of drug, as initial treatment, provides the most effective long-term control of symptoms and best quality of life for people with early Parkinson's disease.
  
  
  METHODS
  In this pragmatic, open-label randomised trial, patients newly diagnosed with Parkinson's disease were randomly assigned (by telephone call to a central office; 1:1:1) between levodopa-sparing therapy (dopamine agonists or MAOBI) and levodopa alone. Patients and investigators were not masked to group assignment. Primary outcomes were the mobility dimension on the 39-item patient-rated Parkinson's disease questionnaire (PDQ-39) quality-of-life scale (range 0-100 with six points defined as the minimally important difference) and cost-effectiveness. Analysis was intention to treat. This trial is registered, number ISRCTN69812316.
  
  
  RESULTS
  Between Nov 9, 2000, and Dec 22, 2009, 1620 patients were assigned to study groups (528 to levodopa, 632 to dopamine agonist, 460 to MAOBI). With 3-year median follow-up, PDQ-39 mobility scores averaged 1·8 points (95% CI 0·5-3·0, p=0·005) better in patients randomly assigned to levodopa than those assigned to levodopa-sparing therapy, with no increase or attrition of benefit during 7 years' observation. PDQ-39 mobility scores were 1·4 points (95% CI 0·0-2·9, p=0·05) better in patients allocated MAOBI than in those allocated dopamine agonists. EQ-5D utility scores averaged 0·03 (95% CI 0·01-0·05; p=0·0002) better with levodopa than with levodopa-sparing therapy; rates of dementia (hazard ratio [HR] 0·81, 95% CI 0·61-1·08, p=0·14), admissions to institutions (0·86, 0·63-1·18; p=0·4), and death (0·85, 0·69-1·06, p=0·17) were not significantly different, but the upper CIs precluded any substantial increase with levodopa compared with levodopa-sparing therapy. 179 (28%) of 632 patients allocated dopamine agonists and 104 (23%) of 460 patients allocated MAOBI discontinued allocated treatment because of side-effects compared with 11 (2%) of 528 patients allocated levodopa (p<0·0001).
  
  
  CONCLUSIONS
  Very small but persistent benefits are shown for patient-rated mobility scores when treatment is initiated with levodopa compared with levodopa-sparing therapy. MAOBI as initial levodopa-sparing therapy was at least as effective as dopamine agonists.
  
  
  BACKGROUND
  UK National Institute for Health Research Health Technology Assessment Programme and UK Department of Health.
authors.forename: Richard
authors.initials: R
authors.lastname: Gray
authors.forename: Natalie
authors.initials: N
authors.lastname: Ives
authors.forename: Caroline
authors.initials: C
authors.lastname: Rick
authors.forename: Smitaa
authors.initials: S
authors.lastname: Patel
authors.forename: Alastair
authors.initials: A
authors.lastname: Gray
authors.forename: Crispin
authors.initials: C
authors.lastname: Jenkinson
authors.forename: Emma
authors.initials: E
authors.lastname: McIntosh
authors.forename: Keith
authors.initials: K
authors.lastname: Wheatley
authors.forename: Adrian
authors.initials: A
authors.lastname: Williams
authors.forename: Carl E
authors.initials: CE
authors.lastname: Clarke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000187:drug effects; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D008996:Monoamine Oxidase Inhibitors; D007980:Levodopa; D008995:Monoamine Oxidase