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Open-label placebo reduces fatigue in cancer survivors: a randomized trial



Cancer-related fatigue (CRF) is a common and challenging late effect for many cancer survivors. Clinical trials demonstrate robust placebo effects on CRF in blinded trials. Recently, open-label placebo (OLP) has been shown to improve a variety of symptoms in other populations. We conducted a randomized controlled trial to investigate the effect of OLP on CRF in cancer survivors, and to explore biologic and psychological correlates of placebo efficacy.


Forty cancer survivors (92.5% female; mean age 47.3 years) were randomized to OLP or no treatment control. OLP participants were prescribed two placebo tablets twice daily, for 3 weeks. All participants completed assessments at Baseline, Day 8, and Day 22. The primary endpoint was change in CRF (FACIT-F), and secondary outcomes included exercise frequency, mood, and quality of life. We examined whether personality characteristics or a genetic variation important in dopamine catabolism (catechol-O-methyltransferase; COMT) affected the placebo response.


The OLP group reported significantly improved CRF at both Day 8 (p = 0.005) and Day 22 (p = .02), while the control group did not (ps > .05). CRF improvement differed by COMT genotype, but was not associated with personality characteristics. Marginal improvements were noted in the placebo group for some secondary outcomes (exercise frequency and quality of life), but not in the control group.


Results demonstrate that even when administered openly, placebos improve CRF in cancer survivors and dopaminergic systems may be associated with this response. This novel research has meaningful implications for the use of OLP in symptom management for cancer survivors.

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The authors thank Ted J. Kaptchuk, John M. Kelley, and Irving Kirsch for their valuable consultation.


This study was funded by the Foundation for the Science of the Therapeutic Encounter.

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Corresponding author

Correspondence to Christopher J. Recklitis.

Ethics declarations

Study procedures were approved by the hospital IRB and registered in the (NCT no. 02452710). All participants gave a written consent.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Zhou, E.S., Hall, K.T., Michaud, A.L. et al. Open-label placebo reduces fatigue in cancer survivors: a randomized trial. Support Care Cancer 27, 2179–2187 (2019).

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  • Open-label placebo
  • Cancer-related fatigue, cancer survivors
  • Genetics
  • Quality of life