A systematic review of adverse events in placebo groups of anti-migraine clinical trials

Amanzio, Martina; Corazzini, Luca Latini; Vase, Lene; Benedetti, Fabrizio

doi:10.1016/j.pain.2009.07.010

Cited by 232Pain Management and Placebo EffectMigraine and Headache StudiesStatistical Methods in Clinical Trials

A systematic review of adverse events in placebo groups of anti-migraine clinical trials

Amanzio, Martina, Corazzini, Luca Latini, Vase, Lene, Benedetti, Fabrizio·2009·Pain

DOI 10.1016/j.pain.2009.07.010

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Abstract

In analgesic clinical trials, adverse events are reported for the painkiller under evaluation and compared with adverse events in the placebo group. Interestingly, patients who receive the placebo often report a high frequency of adverse events, but little is understood about the nature of these negative effects. In the present study, we compared the rates of adverse events reported in the placebo arms of clinical trials for three classes of anti-migraine drugs: NSAIDs, triptans and anticonvulsants. We identified 73 clinical trials in 69 studies describing adverse events in placebo groups: 8 were clinical trials with NSAIDs, 56 were trials with triptans, and 9 were trials with anticonvulsants. Studies were selected of all Medline/PubMed or CENTRAL referenced trials published until 2007. Adverse event profiles of the three classes were compared using a systematic review approach. We found that the rate of adverse events in the placebo arms of trials with anti-migraine drugs was high. In addition, and most interestingly, the adverse events in the placebo arms corresponded to those of the anti-migraine medication against which the placebo was compared. For example, anorexia and memory difficulties, which are typical adverse events of anticonvulsants, were present only in the placebo arm of these trials. These results suggest that the adverse events in placebo arms of clinical trials of anti-migraine medications depend on the adverse events of the active medication against which the placebo is compared. These findings are in accordance with the expectation theory of placebo and nocebo effects.

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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 Amanzio et al., 2009

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Authors: Amanzio, M., Corazzini, L. L., Vase, L., & Benedetti, F.
Affiliations: Aarhus University (DK)
University of Turin (IT)
Corresponding author: Amanzio, Martina
ORCID: Amanzio, Martina
Vase, Lene
Benedetti, Fabrizio
Venue: Pain
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2009-12
Volume: 146
Issue: 3
Pages: 261-269
ISSN: 0304-3959 (ISSN-L)
DOI: 10.1016/j.pain.2009.07.010
OpenAlex: W2064879719
Cited by: 232
References: 90
Citations by year: 2026: 5 · 2025: 12 · 2024: 7 · 2023: 11 · 2022: 13 · 2021: 11 · 2020: 17 · 2019: 23 · 2018: 13 · 2017: 9 · 2016: 18 · 2015: 16 · 2014: 23 · 2013: 11 · 2012: 20
FWCI: 0.99
Type: journal article
Language: en
Open access: closed
Locations: Pain (publishedVersion)
PubMed (publishedVersion)
Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Funders: Regione Piemonte
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
Health Sciences › Medicine › Psychiatry and Mental health › Migraine and Headache Studies
Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
Keywords: antimigraine drugs, migraine, triptans, nonsteroidal anti-inflammatory drugs, antiepileptic drugs, adverse event profiles, nocebo effect
MeSH terms: Analgesics, Anti-Inflammatory Agents, Non-Steroidal, Anticonvulsants, Data Interpretation, Statistical, Ethnicity, Humans, Migraine Disorders, Tryptamines, Randomized Controlled Trials as Topic, Serotonin Receptor Agonists

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A systematic review of adverse events in placebo groups of anti-migraine clinical trials

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