title: The effect of pramipexole on mood and motivational symptoms in Parkinson's disease: a meta-analysis of placebo-controlled studies.
abstract: BACKGROUND
  Mood and motivational symptoms have been reported in up to 35% and 51%, respectively, of patients with Parkinson's disease (PD). Preliminary evidence indicates that pramipexole may have a positive effect on these symptoms.
  
  
  OBJECTIVE
  This analysis was conducted to evaluate the effects of pramipexole on mood and motivational symptoms in patients with PD.
  
  
  METHODS
  Data for the meta-analysis were extracted from all randomized, double-blind, placebo-controlled trials of pramipexole in the manufacturer's database that included part I of the Unified Parkinson's Disease Rating Scale (UPDRS) as an outcome measure. Only patients with baseline scores >0 (range, 0-4) on item 3 (mood) and item 4 (motivation) were included. Separate analyses were performed for mood and motivational symptoms. The outcome of interest was improvement in scores, with no improvement including both unchanged and increased scores. Odds ratios (ORs), 95% CIs, and Cochran-Mantel-Haenszel tests were calculated to compare rates of improvement and no improvement, stratified by trial.
  
  
  RESULTS
  Fourteen randomized, double-blind, placebo-controlled trials of pramipexole were identified, all employing the severity of motor symptoms of PD as a primary outcome. Seven of these trials (N = 1296) employed part I of the UPDRS as a secondary outcome measure and were included in the meta-analysis; no other measure of mood or motivational symptoms was used in any of the 14 studies. Six of the 7 studies included patients with motor fluctuations due to levodo-pa treatment, and the remaining study included patients who did not yet require levodopa. Six studies were published in peer-reviewed journals, and all 7 were included in the New Drug Application for pramipexole. The published study reports were usually limited to motor symptoms; only 1 reported on mood and motivation. However, for the purpose of this meta-analysis, the authors had access to data that were not reported in the original publications. In the pooled data set, 480 patients (59.8% male; mean age, 63.3 years) had a baseline score >0 on item 3 (mood). These mood symptoms improved in 64.7% of patients treated with pramipexole and 43.4% of those receiving placebo (OR weighted by trial = 2.41; P < 0.001). Five hundred seventy patients (64.9% male; mean age, 64.1 years) had a baseline score >0 on item 4 (motivation). These motivational symptoms improved in 63.2% of patients treated with pramipexole and 45.0% of those receiving placebo (OR weighted by trial = 2.06; P < 0.001).
  
  
  CONCLUSIONS
  This meta-analysis of 7 randomized controlled trials suggests that pramipexole had a beneficial effect on mood and motivational symptoms in PD patients who did not have major depressive disorder. The clinical value of pramipexole in the treatment of depressive and apathetic syndromes requires further investigation.
authors.affiliation: Department of Psychiatry, Maastricht University Hospital, Maastricht, The Netherlands. a.leentjens@np.unimaas.nl
authors.forename: Albert F G
authors.initials: AF
authors.lastname: Leentjens
authors.forename: Jürgen
authors.initials: J
authors.lastname: Koester
authors.forename: Barbara
authors.initials: B
authors.lastname: Fruh
authors.forename: D Toby S
authors.initials: DT
authors.lastname: Shephard
authors.forename: Paolo
authors.initials: P
authors.lastname: Barone
authors.forename: John J G
authors.initials: JJ
authors.lastname: Houben
mesh_terms: D000339:Affect / Q000187:drug effects*; D000368:Aged; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use*; D052160:Benzothiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009042:Motivation; D016017:Odds Ratio; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D000077487:Pramipexole; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index
chemical_list: D000978:Antiparkinson Agents; D052160:Benzothiazoles; D000077487:Pramipexole