Nocebo in motor neuron disease: systematic review and meta-analysis of placebo-controlled clinical trials

Abstract

Introduction: Nocebo is very prevalent among neurological disorders, resulting in low adherence and treatment outcome. We sought to examine the AEs following placebo administration in placebo-controlled randomised clinical trials (RCTs) for motor neuron disease (MND). Methods: After a systematic literature search for RCTs for MND pharmacotherapy treatments, we assessed the number of discontinuations because of placebo intolerance. Results: Data were extracted from 12 RCTs fulfilling our search criteria. Approximately eight in 10 placebo-treated patients (78.3%, 95% CI 74.3–82.0%) reported at least one AE and approximately one in 12 placebo-treated patients discontinued placebo treatment because of AEs (8.4%, 95% CI 6.7–10.4%). All patients participating in the MND trials reported similar AEs independently of the study arm to which they belonged. Conclusion: Our study indicates significant nocebo in trials for MND treatment, adversely affecting adherence and efficacy of current treatments in clinical practice, with additional implications for trial design.

Keywords:

• Nocebo
• placebo
• motor neuron disease
• adverse events
• trial design

Acknowledgements

We are sincerely thankful to Dr Stamatina Iliodromiti for her contribution to the statistical analysis.

Declaration of interest

Dr Zis, Miss Shafiq and Dr Mitsikostas report no disclosures related to the context of this article.