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Nonspecific Medication Side Effects and the Nocebo Phenomenon
Open accessAbstract
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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In the citing paper
“This discrepancy may be attributed to nonpharmacological processes, such as nocebo effects, due to the commonality of symptoms.”
From Incidence and Nature of Antidepressant Discontinuation Symptoms (2025) · cites this paper as [42]
In the citing paper
“Undue emphasis on discontinuation effects may increase the likelihood of real and debilitating symptoms, which arise (or are maintained) via processes distinct from pharmacological mechanisms (eg, nocebo effects).”
From Incidence and Nature of Antidepressant Discontinuation Symptoms (2025) · cites this paper as [42]
In the citing paper
“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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Metadata
- 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
- 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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