Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.

Nocebo in Fibromyalgia: Meta-Analysis of Placebo-Controlled Clinical Trials and Implications for Practice.

Mitsikostas1,  DD, Chalarakis1,  NG, Mantonakis1,  LI, Delicha2,  E., Sfikakis2,  PP

Naval Hospital, Athens, Greece, Athens, Greece
First Department of Propaedeutic and Internal Medicine, Laiko, Athens University Medical School, Greece, Athens, Greece


Poor medication adherence has long been observed in clinical practice in patients with fibromyalgia. This may result in treatment failure and/or increased total healthcare costs, and can be partly related to nocebo. Nocebo refers to adverse effects generated by patients' fear that medical treatment will likely harm instead of heal and can be assessed in placebo-controlled randomized clinical trials (RCTs). The present meta-analysis examined adverse effects following placebo administration in RCTs for fibromyalgia.


Following a systematic Medline search for RCTs for fibromyalgia pharmacologic monotherapy treatment published between 2001–2010, we assessed percentages of placebo-treated patients reporting at least one adverse effect or discontinuing due to placebo intolerance and searched for factors influencing nocebo's extent. Percentages were compared to those revealed by similarly performed meta-analyses of placebo-controlled RCT's for multiple sclerosis (Mult Scler, 2010;16:816–828) and primary headaches (Cephalalgia 2011;31:550–61)


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 adverse effect, and 9.5% (95%CI:8.3%–10.9%) discontinued placebo treatment due to intolerance. Adverse effects in placebo arms corresponded quantitatively and qualitatively to those in active drug arms (r>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 fibromyalgia trials were 4-fold and 2-fold higher than in RCT's for multiple sclerosis treatment and migraine preventive treatment, respectively.


Nocebo is remarkably prevalent in fibromyalgia patients participating in RCTs probably being a serious confounding factor. Since 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 seems to be important for fibromyalgia outcome.

To cite this abstract, please use the following information:
Mitsikostas, DD, Chalarakis, NG, Mantonakis, LI, Delicha, E., Sfikakis, PP; Nocebo in Fibromyalgia: Meta-Analysis of Placebo-Controlled Clinical Trials and Implications for Practice. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :739

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