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Nocebo effect in Parkinson’s disease : a systematic review and meta-analysis

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Resumo:Background: The placebo effect is well recognized in Parkinson’s disease (PD) and is thought to be at least in part the result of an increase in dopaminergic neurotransmission. Its counterpart, the nocebo effect, remains ill-characterized. Objective: To estimate the nocebo response in PD, and characterize its determinants. Methods: Databases were searched up to February 2017. Randomized, parallel-designed, placebo-controlled trials of patients with PD were included. Nocebo response was defined as the proportion of patients experiencing adverse events in the placebo arm. It was further characterized as the proportion of withdrawals, withdrawals due to AE and deaths in the placebo arm. Random-effects meta-analysis was used to pool data. Statistical heterogeneity was assessed with I2 statistic. The same analyses were repeated with data from the intervention arm to provide a term of comparison. Results: We included 239 randomized controlled trials (47,797 participants). Pooled nocebo response was 55,8% (95% CI 51,5%–60,1%, 149 trials; I2=97.5%). 13,9% (95% CI 12,4%– 15,4%, 229 trials; I2=90,54%) patients withdrew from trials, 5,7% (95% CI 5,0%–6,4%, 222 trials; I2=72,44%) did it because of AE and 0,6% (95% CI 0,5%–0,7%, 231 trials; I2=0%) died during follow up. Similar proportions were identified in patients in intervention arms. Conclusion: The magnitude of the nocebo response in parallel-designed randomized clinical trials in PD is substantial. This information should be integrated in the evaluation, planning and designing of future clinical trials.
Autores principais:Rato, Miguel Leal
Assunto:Farmacologia clínica Doença de Parkinson Placebo Nocebo
Ano:2017
País:Portugal
Tipo de documento:dissertação de mestrado
Tipo de acesso:acesso restrito
Instituição associada:Universidade de Lisboa
Idioma:inglês
Origem:Repositório da Universidade de Lisboa
Descrição
Resumo:Background: The placebo effect is well recognized in Parkinson’s disease (PD) and is thought to be at least in part the result of an increase in dopaminergic neurotransmission. Its counterpart, the nocebo effect, remains ill-characterized. Objective: To estimate the nocebo response in PD, and characterize its determinants. Methods: Databases were searched up to February 2017. Randomized, parallel-designed, placebo-controlled trials of patients with PD were included. Nocebo response was defined as the proportion of patients experiencing adverse events in the placebo arm. It was further characterized as the proportion of withdrawals, withdrawals due to AE and deaths in the placebo arm. Random-effects meta-analysis was used to pool data. Statistical heterogeneity was assessed with I2 statistic. The same analyses were repeated with data from the intervention arm to provide a term of comparison. Results: We included 239 randomized controlled trials (47,797 participants). Pooled nocebo response was 55,8% (95% CI 51,5%–60,1%, 149 trials; I2=97.5%). 13,9% (95% CI 12,4%– 15,4%, 229 trials; I2=90,54%) patients withdrew from trials, 5,7% (95% CI 5,0%–6,4%, 222 trials; I2=72,44%) did it because of AE and 0,6% (95% CI 0,5%–0,7%, 231 trials; I2=0%) died during follow up. Similar proportions were identified in patients in intervention arms. Conclusion: The magnitude of the nocebo response in parallel-designed randomized clinical trials in PD is substantial. This information should be integrated in the evaluation, planning and designing of future clinical trials.