P Stathis1, M Smpiliris1, S Konitsiotis2, D D Mitsikostas3. 1. Neurology Department, Sismanoglion Hospital, Athens, Greece. 2. Neurology Department, University of Ioannina, Ioannina, Greece. 3. Neurology Department, Athens Naval Hospital, Athens, Greece.
Abstract
BACKGROUND AND PURPOSE: Nocebo refers to adverse events (AEs) generated by patient's negative expectations that medical treatment will likely harm instead of heal and can be assessed in placebo-controlled randomized controlled trials (RCTs). We examined AEs following placebo administration in RCTs for Parkinson's disease (PD). METHODS: After a systematic Medline search for RCTs for PD pharmacologic treatments published between 2000 and 2010, we assessed percentages of placebo-treated patients reporting at least one AE or discontinuing due to placebo intolerance and searched for factors influencing nocebo's extent. RESULTS: Data were extracted from 41 RCTs fulfilling search criteria. Of 3544 placebo-treated patients, 64.7% (95% CI: 53.6-74.4) reported at least one AE and 8.8% (95% CI: 6.8-11.5) discontinued placebo treatment due to intolerance. The number of AEs per 100 person-months was 25.9 (95% CI: 16.8-39.8). Nocebo dropout rate was positively related to study population size and year of publication. Increased number of AEs per 100 person-months was negatively correlated with the duration of treatment. AE rates, dropout rates, and AEs per 100 person-months in placebo- and active drug-treated patients were strongly correlated (r = 0.941, 0.695, and 0.824, respectively). CONCLUSIONS: Our analysis indicates a significant dropout rate related to nocebo in trials for PD treatment. Adherence and efficacy may be adversely affected with additional implications for clinical practice.
BACKGROUND AND PURPOSE: Nocebo refers to adverse events (AEs) generated by patient's negative expectations that medical treatment will likely harm instead of heal and can be assessed in placebo-controlled randomized controlled trials (RCTs). We examined AEs following placebo administration in RCTs for Parkinson's disease (PD). METHODS: After a systematic Medline search for RCTs for PD pharmacologic treatments published between 2000 and 2010, we assessed percentages of placebo-treated patients reporting at least one AE or discontinuing due to placebo intolerance and searched for factors influencing nocebo's extent. RESULTS: Data were extracted from 41 RCTs fulfilling search criteria. Of 3544 placebo-treated patients, 64.7% (95% CI: 53.6-74.4) reported at least one AE and 8.8% (95% CI: 6.8-11.5) discontinued placebo treatment due to intolerance. The number of AEs per 100 person-months was 25.9 (95% CI: 16.8-39.8). Nocebo dropout rate was positively related to study population size and year of publication. Increased number of AEs per 100 person-months was negatively correlated with the duration of treatment. AE rates, dropout rates, and AEs per 100 person-months in placebo- and active drug-treated patients were strongly correlated (r = 0.941, 0.695, and 0.824, respectively). CONCLUSIONS: Our analysis indicates a significant dropout rate related to nocebo in trials for PD treatment. Adherence and efficacy may be adversely affected with additional implications for clinical practice.