Background: Nocebo refers to adverse effects (AEs) generated by negative expectations that medical treatment will likely harm instead of heal and can be assessed in placebo-controlled randomized clinical trials (RCTs). We examined AEs following placebo administration in RCTs for fibromyalgia (FM), a condition characterized by patients' poor medication adherence, which may affect outcome and/or increase healthcare costs.
Methods: Following a systematic Medline search for RCTs for FM pharmacologic treatment published between 2001 and 2010, we assessed percentages of placebo-treated patients reporting at least one AE or discontinuing because of placebo intolerance and searched for factors influencing nocebo's extent. Percentages were compared with those revealed by similar meta-analyses of RCTs for multiple sclerosis and primary headaches.
Results: Data were extracted from 16 RCTs fulfilling search criteria. Of 2026 placebo-treated patients, 67.2% (95%CI: 51.0-81.5%) reported at least one AE, and 9.5% (95%CI: 8.3-10.9%) discontinued placebo treatment because of intolerance. AEs in placebo arms corresponded quantitatively and qualitatively to those in active drug arms (ρ > 0.88, P < 0.0001). Younger age and larger placebo arm size were associated with increased dropout rates. Patients with depression were more likely to withdraw from trials. Nocebo dropouts in FM trials were fourfold and twofold higher than in RCTs for multiple sclerosis treatment and migraine preventive treatment, respectively.
Conclusions: Nocebo is remarkably prevalent in FM patients participating in RCTs. Because nocebo contributes to drug intolerance and treatment failure in clinical practice, identification of predisposing factors and efforts to prevent nocebo by educating these patients appropriately may be important for FM outcome.
© 2011 The Author(s). European Journal of Neurology © 2011 EFNS.