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A meta-analytic approach to estimating nocebo effects in neuropathic pain trials

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Abstract

The development of non-specific adverse effects following the administration of an active or inert substance is referred to as nocebo phenomenon. We aimed to estimate the frequency and severity of nocebo responses in clinical trials of pharmacological treatments for neuropathic pain. A systematic Medline search for all randomized, placebo-controlled neuropathic pain trials published between 2000 and 2010 was carried out. Meta-analysis of the frequency of nocebo responses was performed by pooling the percentage of placebo-treated patients that exhibited drug-related adverse events. Nocebo severity was calculated from the percentage of placebo-treated patients that dropped out due to drug-related adverse events. The pooled frequency of nocebo responses in neuropathic pain trials was 52.0% (95% CI: 35.7–67.9) and the pooled nocebo severity was 6.0% (95% CI: 4.5–8.0). Meta-regression analysis revealed an association between the frequency of nocebo responses and the percentage of females in the placebo-treated group (p = 0.0028). Furthermore, nocebo severity displayed a significant association with the study population (p = 0.0386). Our data indicates a powerful nocebo effect in neuropathic pain trials that may be influenced by gender- and population-related factors. A strong nocebo effect may be adversely affecting adherence and efficacy of current treatments for neuropathic pain in clinical practice.

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Acknowledgments

The authors thank Mrs. Evie Delicha, MSc for her expert advice on the statistical analysis.

Conflicts of interest

Dr. D. Papadopoulos reports no disclosures. Dr. D.D. Mitsikostas received honoraria for lecturing, traveling and research grants from Bayer-Schering, Merck-Serono, MSD, Novartis, Pfizer, Lilly, and UCB. He is a member of the scientific board of Merck-Serono, Greece, Bayer-Schering, Greece, and Novartis Greece. No funding source had a role in the conception or preparation of this article.

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  1. Department of Neurology, Athens Naval Hospital, 70 Deinokratous Street, 115-21, Athens, Greece

    Dimitrios Papadopoulos & Dimos Dimitrios Mitsikostas

  2. Neurology Section, Evangelismos General Hospital, Athens, Greece

    Dimitrios Papadopoulos

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  1. Dimitrios Papadopoulos
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  2. Dimos Dimitrios Mitsikostas
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Correspondence to Dimos Dimitrios Mitsikostas.

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Papadopoulos, D., Mitsikostas, D.D. A meta-analytic approach to estimating nocebo effects in neuropathic pain trials. J Neurol 259, 436–447 (2012). https://doi.org/10.1007/s00415-011-6197-4

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  • DOI: https://doi.org/10.1007/s00415-011-6197-4

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