Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 8, 5

The Nocebo Effect as a Source of Bias in the Assessment of Treatment Effects


The Nocebo Effect as a Source of Bias in the Assessment of Treatment Effects

Karolina Wartolowska. F1000Res.


The term nocebo effect refers to the harmful outcomes that result from people's negative beliefs, anticipations, or experiences related to the treatment rather than the pharmacological properties of the treatment. These outcomes may include a worsening of symptoms, a lack of expected improvement, or adverse events, and they may occur after the active treatment and the placebo that is supposed to imitate it. The nocebo effect is always unwanted and may distort estimates of treatment effectiveness and safety; moreover, it may cause discontinuation of therapy or withdrawal from a trial. The nocebo effect may be unintentionally evoked by the explanations given by healthcare professionals during a clinical consultation or consent procedures, or by information from other patients, the media, or the Internet. Moreover, it may be a consequence of previous bad experiences with the treatment, through learning and conditioning, and the conditioning may happen without patients' conscious awareness. In trial settings, a study design, for example lack of blinding, may introduce bias from the nocebo effect. Unlike the placebo effect, which is usually taken into consideration while interpreting treatment outcomes and controlled for in clinical trials, the nocebo effect is under-recognised by clinical researchers and clinicians. This is worrying, because the nocebo phenomenon is common and may have potentially negative consequences for the results of clinical treatment and trials. It is therefore important that doctors and medical researchers consider any potential nocebo effect while assessing the treatment effect and try to minimise it through careful choice and phrasing of treatment-related information given to patients.

Keywords: Adverse Events in Clinical Trials; Nocebo Effect; Placebo Group; Randomised Clinical Trial (RCT); Review (article).

Conflict of interest statement

No competing interests were disclosed.

Similar articles

See all similar articles


    1. Al Ameri MN, Whittaker C, Tucker A, et al. : A survey to determine the views of renal transplant patients on generic substitution in the UK. Transpl Int. 2011;24(8):770–779. 10.1111/j.1432-2277.2011.01268.x - DOI - PubMed
    1. Amanzio M, Corazzini LL, Vase L, et al. : A systematic review of adverse events in placebo groups of anti-migraine clinical trials. Pain. 2009;146(3):261–269. 10.1016/j.pain.2009.07.010 - DOI - PubMed
    1. Aslaksen PM, Lyby PS: Fear of pain potentiates nocebo hyperalgesia. J Pain Res. 2015;8:703–710. 10.2147/JPR.S91923 - DOI - PMC - PubMed
    1. Aslaksen PM, Zwarg ML, Eilertsen HI, et al. : Opposite effects of the same drug: reversal of topical analgesia by nocebo information. Pain. 2015;156(1):39–46. 10.1016/j.pain.0000000000000004 - DOI - PubMed
    1. Babel P, Bajcar EA, Adamczyk W, et al. : Classical conditioning without verbal suggestions elicits placebo analgesia and nocebo hyperalgesia. PLoS One. 2017;12(7):e0181856. 10.1371/journal.pone.0181856 - DOI - PMC - PubMed

Grant support

The author(s) declared that no grants were involved in supporting this work.

LinkOut - more resources