Nonspecific medication side effects and the nocebo phenomenon

Barsky, Arthur J.

doi:10.1001/jama.287.5.622

Cited by 784Pain Management and Placebo EffectPsychosomatic Disorders and Their TreatmentsPharmacovigilance and Adverse Drug Reactions

Nonspecific medication side effects and the nocebo phenomenon

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Barsky, Arthur J.·2002·JAMA

DOI 10.1001/jama.287.5.622

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Abstract

Patients taking active medications frequently experience adverse, nonspecific side effects that are not a direct result of the specific pharmacological action of the drug. Although this phenomenon is common, distressing, and costly, it is rarely studied and poorly understood. The nocebo phenomenon, in which placebos produce adverse side effects, offers some insight into nonspecific side effect reporting. We performed a focused review of the literature, which identified several factors that appear to be associated with the nocebo phenomenon and/or reporting of nonspecific side effects while taking active medication: the patient's expectations of adverse effects at the outset of treatment; a process of conditioning in which the patient learns from prior experiences to associate medication-taking with somatic symptoms; certain psychological characteristics such as anxiety, depression, and the tendency to somatize; and situational and contextual factors. Physicians and other health care personnel can attempt to ameliorate nonspecific side effects to active medications by identifying in advance those patients most at risk for developing them and by using a collaborative relationship with the patient to explain and help the patient to understand and tolerate these bothersome but nonharmful symptoms.

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Negative expectations may play a role in producing side effects and adverse events during trials and treatment.
“Similarly, there is evidence suggesting that negative expectations can contribute to a variety of side effects and adverse events in clinical trials and medical care (Amanzio et al., 2009; Barsky et al., 2002; Colloca and Finniss, 2012; Petersen et al., 2014).”
From Distinct neural representations of placebo and nocebo effects (2015) · cites this paper as Barsky et al., 2002

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Authors: Barsky, A. J.
Affiliations: Brigham and Women's Hospital (US)
Corresponding author: Barsky, Arthur J.
Venue: JAMA
Publisher: American Medical Association (AMA)
Published: 2002-02-06
Volume: 287
Issue: 5
Pages: 622
ISSN: 0002-9955 (ISSN-L)
0098-7484
DOI: 10.1001/jama.287.5.622
OpenAlex: W2030711540
Cited by: 784
References: 69
Citations by year: 2026: 19 · 2025: 36 · 2024: 23 · 2023: 34 · 2022: 54 · 2021: 49 · 2020: 47 · 2019: 53 · 2018: 45 · 2017: 42 · 2016: 39 · 2015: 33 · 2014: 31 · 2013: 27 · 2012: 31
FWCI: 12.69
Type: journal article
Language: en
Open access: green
dash.harvard.edu
Licence: cc-by
Locations: JAMA (publishedVersion)
PubMed (publishedVersion)
Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
Keywords: nocebo effect, adverse drug reactions, placebo effect, patient expectations, conditioning, anxiety, depression, somatization, patient-physician communication, risk factors
MeSH terms: Attitude to Health, Drug Therapy, Humans, Negativism, Placebos, Risk Factors, Effect Modifier, Epidemiologic, Placebo Effect, Drug-Related Side Effects and Adverse Reactions

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Nonspecific medication side effects and the nocebo phenomenon

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