Skip to main content

Advertisement

SpringerLink
Log in

Experiences of Patients Taking Conditioned Open-Label Placebos for Reduction of Postoperative Pain and Opioid Exposure After Spine Surgery

  • Full length manuscript
  • Published:
International Journal of Behavioral Medicine Aims and scope Submit manuscript

Abstract

Background

Pain after spine surgery is difficult to manage, often requiring the use of opioid analgesics. While traditional “deceptive” or concealed placebo has been studied in trials and laboratory experiments, the acceptability and patient experience of taking honestly prescribed placebos, such as “open-label” placebo (non-deceptive placebo), or conditioned placebo (pairing placebo with another active pharmaceutical) is relatively unexamined.

Methods

Qualitative thematic analysis was performed using semi-structured, post-treatment interviews with spine surgery patients (n = 18) who had received conditioned open-label placebo (COLP) during the first 2–3 weeks after surgery as part of a RCT. Interview transcripts were reviewed by 3 investigators using an immersion/crystallization approach, followed by iterative large-group discussions with additional investigators, to identify, refine, and codify emergent themes.

Results

Patients’ experiences and perceptions of COLP efficacy varied widely. Some emergent themes included the power of the mind over pain, how COLP might provide distraction from or agency over pain, bandwidth required and engagement with COLP, and its modulation of opioid tapering, as well as negative attitudes toward opioids and pill taking in general. Other themes included uncertainty about COLP efficacy, observations of how personality may relate to COLP efficacy, and a recognition of the greater impact of COLP on reduction of opioid use rather than on pain itself. Interestingly, participant uncertainty, disbelief, and skepticism were not necessarily associated with greater opioid consumption or worse pain.

Conclusion

Participants provided insights into the experience of COLP which may help to guide its future utilization to manage acute pain and tapering from opioids.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Terracina S, Robba C, Prete A, Sergi PG, Bilotta F. Prevention and treatment of postoperative pain after lumbar spine procedures: a systematic review. Pain Pract. 2018;18(7):925–45. https://doi.org/10.1111/papr.12684.

    Article  PubMed  Google Scholar 

  2. Elsarrag M, Soldozy S, Patel P, et al. Enhanced recovery after spine surgery: a systematic review. 2019;46(4):E3. https://doi.org/10.3171/2019.1.Focus18700.

    Article  Google Scholar 

  3. Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ committee on regional anesthesia, executive committee, and administrative council. J Pain. 2016;17(2):131–57.

    Article  PubMed  Google Scholar 

  4. Brummett CM, Waljee JF, Goesling J, et al. New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg. 2017;152(6): e170504. https://doi.org/10.1001/jamasurg.2017.0504.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Menendez ME, Ring D, Bateman BT. Preoperative opioid misuse is associated with increased morbidity and mortality after elective orthopaedic surgery. Clin Orthop Relat Res. 2015;473(7):2402–12. https://doi.org/10.1007/s11999-015-4173-5.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Dunn LK, Yerra S, Fang S, et al. Incidence and risk factors for chronic postoperative opioid use after major spine surgery: a cross-sectional study with longitudinal outcome. Anesth Analg. 2018;127(1):247–54. https://doi.org/10.1213/ane.0000000000003338.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Hansen RN, Pham AT, Böing EA, Lovelace B, Wan GJ, Miller TE. Comparative analysis of length of stay, hospitalization costs, opioid use, and discharge status among spine surgery patients with postoperative pain management including intravenous versus oral acetaminophen. Curr Med Res Opin. 2017;33(5):943–8. https://doi.org/10.1080/03007995.2017.1297702.

    Article  PubMed  Google Scholar 

  8. Brusko GD, Kolcun JPG, Heger JA, et al. Reductions in length of stay, narcotics use, and pain following implementation of an enhanced recovery after surgery program for 1- to 3-level lumbar fusion surgery. Neurosurg Focus. 2019;46(4):E4. https://doi.org/10.3171/2019.1.Focus18692.

    Article  PubMed  Google Scholar 

  9. Hoy D, March L, Brooks P, et al. The global burden of low back pain: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis. 2014;73(6):968–74.

    Article  PubMed  Google Scholar 

  10. Kaptchuk TJ, Hemond CC, Miller FG. Placebos in chronic pain: evidence, theory, ethics, and use in clinical practice. BMJ. 2020;370: m1668. https://doi.org/10.1136/bmj.m1668.

    Article  PubMed  Google Scholar 

  11. Kaptchuk TJ. Intentional ignorance: a history of blind assessment and placebo controls in medicine. Bull Hist Med. 1998;72(3):389–433.

    Article  CAS  PubMed  Google Scholar 

  12. Beecher HK. The powerful placebo. J Am Med Assoc. 1955;159(17):1602–6.

    Article  CAS  PubMed  Google Scholar 

  13. Kirsch I. Response expectancy as a determinant of experience and behavior. Am Psychol. 1985;40(11):1189.

    Article  Google Scholar 

  14. Kirsch I, Weixel LJ. Double-blind versus deceptive administration of a placebo. Behav Neurosci. 1988;102(2):319.

    Article  CAS  PubMed  Google Scholar 

  15. Kaptchuk TJ, Shaw J, Kerr CE, et al. “Maybe I made up the whole thing”: placebos and patients’ experiences in a randomized controlled trial. Cult Med Psychiatry. 2009;33(3):382–411.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Eaves ER, Nichter M, Ritenbaugh C. Ways of hoping: navigating the paradox of hope and despair in chronic pain. Cult Med Psychiatry. 2016;40(1):35–58.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sherman KJ, Cherkin DC, Ichikawa L, et al. Treatment expectations and preferences as predictors of outcome of acupuncture for chronic back pain. Spine. 2010;35(15):1471.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Hsu C, Sherman KJ, Eaves ER, et al. New perspectives on patient expectations of treatment outcomes: results from qualitative interviews with patients seeking complementary and alternative medicine treatments for chronic low back pain. BMC Complement Altern Med. 2014;14(1):1–10.

    Article  Google Scholar 

  19. Finniss DG, Kaptchuk TJ, Miller F, Benedetti F. Biological, clinical, and ethical advances of placebo effects. The Lancet. 2010;375(9715):686–95.

    Article  Google Scholar 

  20. Klinger R, Stuhlreyer J, Schwartz M, Schmitz J, Colloca L. Clinical use of placebo effects in patients with pain disorders. Int Rev Neurobiol. 2018;139:107–28. https://doi.org/10.1016/bs.irn.2018.07.015.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Colloca L, Grillon C. Understanding placebo and nocebo responses for pain management. Curr Pain Headache Rep. 2014;18(6):419.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Finniss DG, Kaptchuk TJ, Miller F, Benedetti F. Placebo effects: biological, clinical and ethical advances. Lancet. 2010;375(9715):686.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Geuter S, Koban L, Wager TD. The cognitive neuroscience of placebo effects: concepts, predictions, and physiology. Annu Rev Neurosci. 2017;40:167–88.

    Article  CAS  PubMed  Google Scholar 

  24. Wager TD, Atlas LY. The neuroscience of placebo effects: connecting context, learning and health. Nat Rev Neurosci. 2015;16(7):403–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zunhammer M, Bingel U, Wager TD. Placebo effects on the neurologic pain signature: a meta-analysis of individual participant functional magnetic resonance imaging data. JAMA Neurol. 2018;75(11):1321–30.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Hall KT, Loscalzo J, Kaptchuk TJ. Genetics and the placebo effect: the placebome. Trends Mol Med. 2015;21(5):285–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Fuchs T, Schlimme JE. Embodiment and psychopathology: a phenomenological perspective. Curr Opin Psychiatry. 2009;22(6):570–5.

    Article  PubMed  Google Scholar 

  28. Frenkel O. A phenomenology of the ‘placebo effect’: taking meaning from the mind to the body. J Med Philos. 2008;33(1):58–79.

    Article  PubMed  Google Scholar 

  29. Ongaro G, Kaptchuk TJ. Symptom perception, placebo effects, and the Bayesian brain. Pain. 2019;160(1):1.

    Article  PubMed  Google Scholar 

  30. Kaptchuk TJ. Open-label placebo: reflections on a research agenda. Perspect Biol Med. 2018;61(3):311–34.

    Article  PubMed  Google Scholar 

  31. Blease CR, Bishop FL, Kaptchuk TJ. Informed consent and clinical trials: where is the placebo effect? BMJ. 2017;356: j463. https://doi.org/10.1136/bmj.j463.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kaptchuk TJ, Miller FG. Open label placebo: can honestly prescribed placebos evoke meaningful therapeutic benefits? BMJ. 2018;363: k3889. https://doi.org/10.1136/bmj.k3889.

    Article  PubMed  PubMed Central  Google Scholar 

  33. von Wernsdorff M, Loef M, Tuschen-Caffier B, Schmidt S. Effects of open-label placebos in clinical trials: a systematic review and meta-analysis. Sci Rep. 2021;11(1):1–14.

    Google Scholar 

  34. Kelley JM, Kaptchuk TJ, Cusin C, Lipkin S, Fava M. Open-label placebo for major depressive disorder: a pilot randomized controlled trial. Psychother Psychosom. 2012;81(5).

  35. Kaptchuk TJ, Friedlander E, Kelley JM, et al. Placebos without deception: a randomized controlled trial in irritable bowel syndrome. PLoS ONE. 2010;5(12): e15591.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hoenemeyer TW, Kaptchuk TJ, Mehta TS, Fontaine KR. Open-label placebo treatment for cancer-related fatigue: a randomized-controlled clinical trial. Sci Rep. 2018;8(1):1–8.

    Article  CAS  Google Scholar 

  37. Carvalho C, Caetano JM, Cunha L, Rebouta P, Kaptchuk TJ, Kirsch I. Open-label placebo treatment in chronic low back pain: a randomized controlled trial. Pain. 2016;157(12):2766–72. https://doi.org/10.1097/j.pain.0000000000000700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kleine-Borgmann J, Schmidt K, Hellmann A, Bingel U. Effects of open-label placebo on pain, functional disability, and spine mobility in patients with chronic back pain: a randomized controlled trial. Pain. 2019;160(12):2891–7.

    Article  PubMed  Google Scholar 

  39. Amanzio M, Benedetti F. Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated specific subsystems. J Neurosci. 1999;19(1):484–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ader R, Mercurio MG, Walton J, et al. Conditioned pharmacotherapeutic effects: a preliminary study. Psychosom Med. 2010;72(2):192.

    Article  PubMed  Google Scholar 

  41. Goebel MU, Meykadeh N, Kou W, Schedlowski M, Hengge UR. Behavioral conditioning of antihistamine effects in patients with allergic rhinitis. Psychother Psychosom. 2008;77(4):227–34.

    Article  PubMed  Google Scholar 

  42. Perlis M, Grandner M, Zee J, et al. Durability of treatment response to zolpidem with three different maintenance regimens: a preliminary study. Sleep Med. 2015;16(9):1160–8.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Sandler AD, Glesne CE, Bodfish JW. Conditioned placebo dose reduction: a new treatment in ADHD? J Develop Behav Pedia: JDBP. 2010;31(5):369.

    Article  Google Scholar 

  44. Kirchhof J, Petrakova L, Brinkhoff A, et al. Learned immunosuppressive placebo responses in renal transplant patients. Proc Natl Acad Sci. 2018;115(16):4223–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Morales-Quezada L, Mesia-Toledo I, Estudillo-Guerra A, et al. Conditioning open-label placebo: a pilot pharmacobehavioral approach for opioid dose reduction and pain control. Pain Rep. 2020;5(4).

  46. Kaptchuk TJ, Hemond CC, Miller FG. Placebos in chronic pain: evidence, theory, ethics, and use in clinical practice. Bmj. 2020;370.

  47. Flowers KM, Patton ME, Hruschak VJ, et al. Conditioned open-label placebo for opioid reduction following spine surgery: a randomized, controlled trial. Pain. 2021.

  48. Hsieh H-F, Shannon SE. Three approaches to qualitative content analysis. Qual Health Res. 2005;15(9):1277–88.

    Article  PubMed  Google Scholar 

  49. Crabtree BF, Crabtree BF, Miller WL. Doing qualitative research: Sage. 1999.

  50. Eaves ER, Sherman KJ, Ritenbaugh C, et al. A qualitative study of changes in expectations over time among patients with chronic low back pain seeking four CAM therapies. BMC Complement Altern Med. 2015;15(1):1–10.

    Article  Google Scholar 

  51. Hull SC, Colloca L, Avins A, et al. Patients’ attitudes about the use of placebo treatments: telephone survey. Bmj. 2013;347.

  52. Ortiz R, Hull SC, Colloca L. Patient attitudes about the clinical use of placebo: qualitative perspectives from a telephone survey. BMJ Open. 2016;6(4): e011012.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Bishop FL, Aizlewood L, Adams AE. When and why placebo-prescribing is acceptable and unacceptable: a focus group study of patients’ views. PLoS ONE. 2014;9(7): e101822.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Bishop FL, Jacobson EE, Shaw JR, Kaptchuk TJ. Scientific tools, fake treatments, or triggers for psychological healing: how clinical trial participants conceptualise placebos. Soc Sci Med. 2012;74(5):767–74.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Tandjung R, Tang H, Fassler M, et al. The patient's perspective of placebo use in daily practice: a qualitative study. Euro J Med Sci. 2014.

  56. Sandler A, Glesne C, Geller G. Children's and parents' perspectives on open‐label use of placebos in the treatment of ADHD. Child: Care, Health Develop 2008;34(1):111–20.

  57. De Pascalis V, Chiaradia C, Carotenuto E. The contribution of suggestibility and expectation to placebo analgesia phenomenon in an experimental setting. Pain. 2002;96(3):393–402.

    Article  PubMed  Google Scholar 

  58. Pollo A, Carlino E, Benedetti F. Placebo mechanisms across different conditions: from the clinical setting to physical performance. Philosophic Transact Royal Soc B: Biol Sci. 2011;366(1572):1790–8.

    Article  Google Scholar 

  59. Price DD, Milling LS, Kirsch I, Duff A, Montgomery GH, Nicholls SS. An analysis of factors that contribute to the magnitude of placebo analgesia in an experimental paradigm. Pain. 1999;83(2):147–56.

    Article  CAS  PubMed  Google Scholar 

  60. Bernstein MH, Magill M, Weiss A-P, et al. Are conditioned open placebos feasible as an adjunctive treatment to opioids? Results from a single-group dose-extender pilot study with acute pain patients. Psychother Psychosom. 2019;88(6):380.

    Article  PubMed  Google Scholar 

  61. Lembo A, Kelley JM, Nee J, et al. Open-label placebo vs double-blind placebo for irritable bowel syndrome: a randomized clinical trial. Pain. 2021;162(9):2428–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Haas JW, Ongaro G, Jacobson E, et al. Patients’ experiences treated with open-label placebo versus double-blind placebo: a mixed methods qualitative study. BMC Psychol. 2022;10(1):1–12.

    Article  Google Scholar 

  63. Locher C, Nascimento AF, Kirsch I, Kossowsky J, Meyer A, Gaab J. Is the rationale more important than deception? A randomized controlled trial of open-label placebo analgesia. Pain. 2017;158(12):2320–8.

    Article  PubMed  Google Scholar 

  64. Locher C, Buergler S, Nascimento AF, Kost L, Blease C, Gaab J. Lay perspectives of the open-label placebo rationale: a qualitative study of participants in an experimental trial. BMJ Open. 2021;11(8): e053346.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Jensen KB, Kaptchuk TJ, Chen X, et al. A neural mechanism for nonconscious activation of conditioned placebo and nocebo responses. Cereb Cortex. 2015;25(10):3903–10.

    Article  PubMed  Google Scholar 

  66. Jensen KB, Kaptchuk TJ, Kirsch I, et al. Nonconscious activation of placebo and nocebo pain responses. Proc Natl Acad Sci. 2012;109(39):15959–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Pan Y, Meister R, Löwe B, Kaptchuk TJ, Buhling KJ, Nestoriuc Y. Open-label placebos for menopausal hot flushes: a randomized controlled trial. Sci Rep. 2020;10(1):1–15.

    Article  Google Scholar 

  68. Lidstone SC, Schulzer M, Dinelle K, et al. Effects of expectation on placebo-induced dopamine release in Parkinson disease. Arch Gen Psychiatry. 2010;67(8):857–65. https://doi.org/10.1001/archgenpsychiatry.2010.88.

    Article  CAS  PubMed  Google Scholar 

  69. Farrar JT, Troxel AB, Haynes K, et al. Effect of variability in the 7-day baseline pain diary on the assay sensitivity of neuropathic pain randomized clinical trials: an ACTTION study. Pain. 2014;155(8):1622–31. https://doi.org/10.1016/j.pain.2014.05.009.

    Article  PubMed  Google Scholar 

  70. Burke MJ. “It’s all in your head”—medicine’s silent epidemic. JAMA Neurol. 2019;76(12):1417–8.

    Article  PubMed  Google Scholar 

  71. Ratnapalan M, Coghlan B, Tan M, et al. Placebos in primary care? A nominal group study explicating UK GP and patient views of six theoretically plausible models of placebo practice. BMJ Open. 2020;10(2).

  72. Stone DA, Kerr CE, Jacobson E, Conboy ScD LA, Kaptchuk TJ. Patient expectations in placebo-controlled randomized clinical trials. J Eval Clin Pract. 2005;11(1):77–84.

    Article  PubMed  Google Scholar 

  73. Polak L. What is wrong with ‘being a pill-taker’? The special case of statins. Sociol Health Illn. 2017;39(4):599–613.

    Article  PubMed  Google Scholar 

  74. Ballou S, Kaptchuk TJ, Hirsch W, et al. Open-label versus double-blind placebo treatment in irritable bowel syndrome: study protocol for a randomized controlled trial. Trials. 2017;18(1):1–15.

    Article  Google Scholar 

  75. Edwards RR, Dworkin RH, Turk DC, et al. Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations. Pain. 2016;157(9):1851.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the nursing staff at Brigham and Women’s Hospital for their cooperation in conducting this trial. Most importantly, we thank the participants of this clinical trial for their time and willingness to participate in this experiment.

Funding

This study was funded by the Foundation for the Study of the Therapeutic Encounter, in conjunction with a seed grant from the Department of Anesthesiology, Perioperative, and Pain Medicine at Brigham and Women’s Hospital.

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02015, USA

    Valerie Hruschak, K. Mikayla Flowers, Emily Schwartz, Robert Edwards & Kristin Schreiber

  2. Lewis Katz School of Medicine, Temple University, Philadelphia, USA

    Megan Patton

  3. Northeastern University, Boston, USA

    Victoria Merchantz

  4. Beth Israel Deaconess Medical Center, Boston, USA

    Ted Kaptchuk

  5. Department of Orthopedic Surgery, Brigham and Women’s Hospital, Boston, USA

    James Kang

  6. Department of Internal Medicine, University of California, Davis, Davis, USA

    Michelle Dossett

Authors
  1. Valerie Hruschak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Mikayla Flowers
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Megan Patton
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Victoria Merchantz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Emily Schwartz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Robert Edwards
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ted Kaptchuk
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. James Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michelle Dossett
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kristin Schreiber
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kristin Schreiber.

Ethics declarations

Ethics 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.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 16 KB)

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hruschak, V., Flowers, K.M., Patton, M. et al. Experiences of Patients Taking Conditioned Open-Label Placebos for Reduction of Postoperative Pain and Opioid Exposure After Spine Surgery. Int.J. Behav. Med. 30, 509–521 (2023). https://doi.org/10.1007/s12529-022-10114-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12529-022-10114-5

Keywords

Search

Navigation