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

Amanzio, Martinaa,b,*; Corazzini, Luca Latinia,b; Vase, Lenec; Benedetti, Fabriziod,e

doi: 10.1016/j.pain.2009.07.010
Research papers

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.

aDepartment of Psychology, University of Turin, Via Verdi 10, 10123 Turin, Italy

bNeuroscience Institute of Turin (NIT), University of Turin, Italy

cDepartment of Psychology, University of Aarhus, Jens Chr. Skous Vej 4, DK – 8000 Århus C, Denmark

dDepartment of Neuroscience, University of Turin Medical School, Corso Raffaello 30, 10125 Turin, Italy

eNational Institute of Neuroscience (INN), Turin, Italy

*Corresponding author. Address: Department of Psychology, University of Turin, Via Verdi 10, 10123 Turin, Italy. Tel.: +39 11 6702468; fax: +39 11 6702061.



Article history:

Received March 24, 2009

Received in revised form June 4, 2009

Accepted July 13, 2009.

© 2009 Lippincott Williams & Wilkins, Inc.
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