Experiences of Patients Taking Conditioned Open-Label Placebos for Reduction of Postoperative Pain and Opioid Exposure After Spine Surgery.
Open-label placebo
Opioid analgesics
Postoperative pain
Psychological conditioning
Qualitative research
Spine surgery
Journal
International journal of behavioral medicine
ISSN: 1532-7558
Titre abrégé: Int J Behav Med
Pays: England
ID NLM: 9421097
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
accepted:
07
07
2022
medline:
3
7
2023
pubmed:
2
8
2022
entrez:
1
8
2022
Statut:
ppublish
Résumé
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. 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. 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. Participants provided insights into the experience of COLP which may help to guide its future utilization to manage acute pain and tapering from opioids.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
Participants provided insights into the experience of COLP which may help to guide its future utilization to manage acute pain and tapering from opioids.
Identifiants
pubmed: 35915346
doi: 10.1007/s12529-022-10114-5
pii: 10.1007/s12529-022-10114-5
doi:
Substances chimiques
Analgesics, Opioid
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
509-521Informations de copyright
© 2022. International Society of Behavioral Medicine.
Références
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 .
doi: 10.1111/papr.12684
pubmed: 29393998
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 .
doi: 10.3171/2019.1.Focus18700
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.
pubmed: 26827847
doi: 10.1016/j.jpain.2015.12.008
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 .
doi: 10.1001/jamasurg.2017.0504
pubmed: 28403427
pmcid: 7050825
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 .
doi: 10.1007/s11999-015-4173-5
pubmed: 25694266
pmcid: 4457771
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 .
doi: 10.1213/ane.0000000000003338
pubmed: 29570151
pmcid: 6487073
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 .
doi: 10.1080/03007995.2017.1297702
pubmed: 28276273
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 .
doi: 10.3171/2019.1.Focus18692
pubmed: 30933921
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.
pubmed: 24665116
doi: 10.1136/annrheumdis-2013-204428
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 .
doi: 10.1136/bmj.m1668
pubmed: 32690477
Kaptchuk TJ. Intentional ignorance: a history of blind assessment and placebo controls in medicine. Bull Hist Med. 1998;72(3):389–433.
pubmed: 9780448
doi: 10.1353/bhm.1998.0159
Beecher HK. The powerful placebo. J Am Med Assoc. 1955;159(17):1602–6.
pubmed: 13271123
doi: 10.1001/jama.1955.02960340022006
Kirsch I. Response expectancy as a determinant of experience and behavior. Am Psychol. 1985;40(11):1189.
doi: 10.1037/0003-066X.40.11.1189
Kirsch I, Weixel LJ. Double-blind versus deceptive administration of a placebo. Behav Neurosci. 1988;102(2):319.
pubmed: 3365327
doi: 10.1037/0735-7044.102.2.319
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.
pubmed: 19597976
pmcid: 2716443
doi: 10.1007/s11013-009-9141-7
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.
pubmed: 26194780
pmcid: 4721951
doi: 10.1007/s11013-015-9465-4
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.
pubmed: 20535051
pmcid: 2895682
doi: 10.1097/BRS.0b013e3181c2a8d3
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.
doi: 10.1186/1472-6882-14-276
Finniss DG, Kaptchuk TJ, Miller F, Benedetti F. Biological, clinical, and ethical advances of placebo effects. The Lancet. 2010;375(9715):686–95.
doi: 10.1016/S0140-6736(09)61706-2
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 .
doi: 10.1016/bs.irn.2018.07.015
pubmed: 30146044
pmcid: 6175283
Colloca L, Grillon C. Understanding placebo and nocebo responses for pain management. Curr Pain Headache Rep. 2014;18(6):419.
pubmed: 24771206
pmcid: 4142751
doi: 10.1007/s11916-014-0419-2
Finniss DG, Kaptchuk TJ, Miller F, Benedetti F. Placebo effects: biological, clinical and ethical advances. Lancet. 2010;375(9715):686.
pubmed: 20171404
pmcid: 2832199
doi: 10.1016/S0140-6736(09)61706-2
Geuter S, Koban L, Wager TD. The cognitive neuroscience of placebo effects: concepts, predictions, and physiology. Annu Rev Neurosci. 2017;40:167–88.
pubmed: 28399689
doi: 10.1146/annurev-neuro-072116-031132
Wager TD, Atlas LY. The neuroscience of placebo effects: connecting context, learning and health. Nat Rev Neurosci. 2015;16(7):403–18.
pubmed: 26087681
pmcid: 6013051
doi: 10.1038/nrn3976
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.
pubmed: 30073258
pmcid: 6248115
doi: 10.1001/jamaneurol.2018.2017
Hall KT, Loscalzo J, Kaptchuk TJ. Genetics and the placebo effect: the placebome. Trends Mol Med. 2015;21(5):285–94.
pubmed: 25883069
pmcid: 4573548
doi: 10.1016/j.molmed.2015.02.009
Fuchs T, Schlimme JE. Embodiment and psychopathology: a phenomenological perspective. Curr Opin Psychiatry. 2009;22(6):570–5.
pubmed: 19730373
doi: 10.1097/YCO.0b013e3283318e5c
Frenkel O. A phenomenology of the ‘placebo effect’: taking meaning from the mind to the body. J Med Philos. 2008;33(1):58–79.
pubmed: 18420551
doi: 10.1093/jmp/jhm005
Ongaro G, Kaptchuk TJ. Symptom perception, placebo effects, and the Bayesian brain. Pain. 2019;160(1):1.
pubmed: 30086114
doi: 10.1097/j.pain.0000000000001367
Kaptchuk TJ. Open-label placebo: reflections on a research agenda. Perspect Biol Med. 2018;61(3):311–34.
pubmed: 30293971
doi: 10.1353/pbm.2018.0045
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 .
doi: 10.1136/bmj.j463
pubmed: 28159769
pmcid: 6888513
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 .
doi: 10.1136/bmj.k3889
pubmed: 30279235
pmcid: 6889847
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.
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).
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.
pubmed: 21203519
pmcid: 3008733
doi: 10.1371/journal.pone.0015591
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.
doi: 10.1038/s41598-018-20993-y
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 .
doi: 10.1097/j.pain.0000000000000700
pubmed: 27755279
pmcid: 5113234
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.
pubmed: 31479068
doi: 10.1097/j.pain.0000000000001683
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.
pubmed: 9870976
pmcid: 6782391
doi: 10.1523/JNEUROSCI.19-01-00484.1999
Ader R, Mercurio MG, Walton J, et al. Conditioned pharmacotherapeutic effects: a preliminary study. Psychosom Med. 2010;72(2):192.
pubmed: 20028830
doi: 10.1097/PSY.0b013e3181cbd38b
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.
pubmed: 18418029
doi: 10.1159/000126074
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.
pubmed: 26298795
pmcid: 4709332
doi: 10.1016/j.sleep.2015.06.015
Sandler AD, Glesne CE, Bodfish JW. Conditioned placebo dose reduction: a new treatment in ADHD? J Develop Behav Pedia: JDBP. 2010;31(5):369.
doi: 10.1097/DBP.0b013e3181e121ed
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.
pubmed: 29610294
pmcid: 5910853
doi: 10.1073/pnas.1720548115
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).
Kaptchuk TJ, Hemond CC, Miller FG. Placebos in chronic pain: evidence, theory, ethics, and use in clinical practice. Bmj. 2020;370.
Flowers KM, Patton ME, Hruschak VJ, et al. Conditioned open-label placebo for opioid reduction following spine surgery: a randomized, controlled trial. Pain. 2021.
Hsieh H-F, Shannon SE. Three approaches to qualitative content analysis. Qual Health Res. 2005;15(9):1277–88.
pubmed: 16204405
doi: 10.1177/1049732305276687
Crabtree BF, Crabtree BF, Miller WL. Doing qualitative research: Sage. 1999.
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.
doi: 10.1186/s12906-015-0531-9
Hull SC, Colloca L, Avins A, et al. Patients’ attitudes about the use of placebo treatments: telephone survey. Bmj. 2013;347.
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.
pubmed: 27044586
pmcid: 4823468
doi: 10.1136/bmjopen-2015-011012
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.
pubmed: 25006673
pmcid: 4089920
doi: 10.1371/journal.pone.0101822
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.
pubmed: 22285289
pmcid: 3288621
doi: 10.1016/j.socscimed.2011.11.020
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.
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.
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.
pubmed: 11973014
doi: 10.1016/S0304-3959(01)00485-7
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.
doi: 10.1098/rstb.2010.0381
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.
pubmed: 10534585
doi: 10.1016/S0304-3959(99)00081-0
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.
pubmed: 31563914
doi: 10.1159/000503038
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.
pubmed: 33605656
pmcid: 8357842
doi: 10.1097/j.pain.0000000000002234
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.
doi: 10.1186/s40359-022-00731-w
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.
pubmed: 28708766
doi: 10.1097/j.pain.0000000000001012
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.
pubmed: 34408060
pmcid: 8375733
doi: 10.1136/bmjopen-2021-053346
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.
pubmed: 25452576
doi: 10.1093/cercor/bhu275
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.
pubmed: 23019380
pmcid: 3465419
doi: 10.1073/pnas.1202056109
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.
doi: 10.1038/s41598-020-77255-z
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 .
doi: 10.1001/archgenpsychiatry.2010.88
pubmed: 20679593
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 .
doi: 10.1016/j.pain.2014.05.009
pubmed: 24831421
Burke MJ. “It’s all in your head”—medicine’s silent epidemic. JAMA Neurol. 2019;76(12):1417–8.
pubmed: 31524927
doi: 10.1001/jamaneurol.2019.3043
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).
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.
pubmed: 15660541
doi: 10.1111/j.1365-2753.2004.00512.x
Polak L. What is wrong with ‘being a pill-taker’? The special case of statins. Sociol Health Illn. 2017;39(4):599–613.
pubmed: 27862018
doi: 10.1111/1467-9566.12509
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.
doi: 10.1186/s13063-017-1964-x
Edwards RR, Dworkin RH, Turk DC, et al. Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations. Pain. 2016;157(9):1851.
pubmed: 27152687
pmcid: 5965275
doi: 10.1097/j.pain.0000000000000602