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Review
. 2017 Jul 31:10:1831-1839.
doi: 10.2147/JPR.S134745. eCollection 2017.

A systematic review of sex differences in the placebo and the nocebo effect

Sara M Vambheim  1 , Magne Arve Flaten  2
Affiliations
Review

A systematic review of sex differences in the placebo and the nocebo effect

Sara M Vambheim et al. J Pain Res. .

Abstract

Objectives: The present review investigated whether there are systematic sex differences in the placebo and the nocebo effect.

Methods: A literature search was conducted in multiple electronic databases. Studies were included if the study compared a group or condition where a placebo was administered to a natural history group or similar cohort.

Results: Eighteen studies were identified - 12 on placebo effects and 6 on nocebo effects. Chi-square tests revealed that 1) males responded more strongly to placebo treatment, and females responded more strongly to nocebo treatment, and 2) males responded with larger placebo effects induced by verbal information, and females responded with larger nocebo effects induced by conditioning procedures.

Conclusion: This review indicates that there are sex differences in the placebo and nocebo effects, probably caused by sex differences in stress, anxiety, and the endogenous opioid system.

Keywords: nocebo hyperalgesia; nocebo response; placebo analgesia; placebo response; sex differences.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

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PRISMA flow diagram.
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References

Reference list of the included studies

    1. Abrams K, Kushner MG. The moderating effects of tension-reduction alcohol outcome expectancies on placebo responding in individuals with social phobia. Addictive Behaviors. 2004;29:1221–1224. - PubMed
    1. Aslaksen PM, Lyby PS. Fear of pain potentiates nocebo hyperalgesia. Journal of Pain Research. 2015;8:703–710. - PMC - PubMed
    1. Aslaksen PM, Bystad M, Vambheim SM, Flaten MA. Gender differences in placebo analgesia: event-related potentials and emotional modulation. Psychosomatic Medicine. 2011;73:193–199. - PubMed
    1. Aslaksen PM, Flaten MA. The roles of physiological and subjective stress in the effectiveness of a placebo on experimentally induced pain. Psychosomatic Medicine. 2008;70:811–818. - PubMed
    1. Bjørkedal E, Flaten MA. Interaction between expectancies and drug effects: an experimental investigation of placebo analgesia with caffeine as an active placebo. Psychopharmacology. 2011;215:2233–4. - PMC - PubMed

References

    1. Flaten MA, al’Absi M. Placebo and placebo effect. In: Gellman MD, Rick Turner J, editors. Encyclopedia of Behavioral Medicine. New York: Springer; 2013. pp. 1497–1499.
    1. Benedetti F. The opposite effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia. Pain. 1996;64(3):535–543. - PubMed
    1. Aslaksen PM, Lyby PS. Fear of pain potentiates nocebo hyperalgesia. J Pain Res. 2015;8:703–710. - PMC - PubMed
    1. Aslaksen PM, Bystad M, Vambheim SM, Flaten MA. Gender differences in placebo analgesia: event-related potentials and emotional modulation. Psychosom Med. 2011;73(2):193–199. - PubMed
    1. Butcher BE, Carmody JJ. Sex differences in analgesic response to ibuprofen are influenced by expectancy: a randomized, crossover, balanced placebo-designed study. Eur J Pain. 2012;16(7):1005–1013. - PubMed

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