• Tiago A Mestre, Prakesh Shah, Connie Marras, George Tomlinson, and Anthony E Lang.
• From the Movement Disorders Centre and Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University Health Network, Division of Neurology (T.A.M., C.M., A.E.L.), the Department of Paediatrics and Institute of Health Policy, Management and Evaluation (P.S.), the Department of Public Health Sciences (G.T.), and the Department of Medicine (T.A.M., C.M., G.T., A.E.L.), University of Toronto; and the Department of Pediatrics (P.S.), Mount Sinai Hospital, Toronto. T.A.M. is currently with the Parkinson's Disease and Movement Disorders Clinic, Division of Neurology, Ottawa Hospital, University of Ottawa.
• Neurology. 2014 Apr 22; 82 (16): 1402-9.

ObjectiveTo study the impact of negative expectation related to receiving a placebo (the "lessebo effect") on efficacy outcome measures of symptomatic treatments in Parkinson disease (PD).MethodsWe conducted meta-analyses of double-blind randomized controlled trials (RCTs) of dopamine agonists in PD and compared the pooled mean score change of the motor section of the Unified Parkinson's Disease Rating Scale (mUPDRS) across active treatment arms according to the presence of a placebo arm or the probability of placebo assignment (0%, <50%, and 50%) of the original RCT. A mixed-effects model was used. Heterogeneity was assessed by subgroup analyses and meta-regression modeling.ResultsA total of 28 study arms were extracted from active-controlled trials (3,277 patients) and 42 from placebo-controlled trials (4,554 patients). The overall difference between groups in the pooled mean score change in the mUPDRS was 1.6 units (95% confidence interval [CI] 0.2, 3.0; p = 0.023), in favor of the active-controlled group. In subgroup analyses, this difference was of higher magnitude in the early PD group without motor fluctuations (3.3 mUPDRS units, 95% CI 1.1, 5.4; p = 0.003) and for study duration ≤ 12 weeks (4.1 mUPDRS units, 95% CI 1.0, 7.2; p = 0.009). There was no between-group difference using probability of placebo assignment as criterion.ConclusionsThis study shows that the use of a placebo can be associated with a clinically significant reduction in the magnitude of change of the mUPDRS after an active treatment in RCTs for PD. These new findings have potential implications in the development of new treatments and appraisal of current treatment options for PD and possibly for other neurologic disorders.

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