安慰剂效应的心理机制及临床应用
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摘要
安慰剂效应在临床治疗中发挥着重要作用,如缓解患者的疼痛及促进患者运动功能康复等。由于临床环境的复杂性,安慰剂效应的产生涉及到患者、医护人员和医疗环境等复杂的心理社会因素。为综合调节这些因素使得安慰剂效应最大化,有效提高整体治疗效果,本研究系统总结了安慰剂效应产生的心理机制,包括预期、条件化、社会观察学习和个体因素的作用;讨论了安慰剂在临床镇痛中的有效性;从患者、医护人员和治疗环境等方面探讨了影响临床中安慰剂效应的因素及相应的调节策略;最后,针对当前安慰剂相关的基础研究向临床转化中所面临的问题提出了可能的解决方案。
To promote the translation of basic findings into clinical practice and to optimize placebo effect in clinical ap-plications,psychological mechanisms and clinical applications of placebo effects were comprehensively reviewed in thepresent study.We firstly summarized the involvement of expectancy,classical conditioning,social learning,and individualfactors in the generation of placebo effects.The interactions among expectancy,conditioning,motivation(e.g.,desire for re-lief),cognition(e.g.,somatic focus),and individual factors(e.g.,emotional state and personality trait) were highlighted.Then,we discussed evidence demonstrating placebo induced analgesic effects for relieving various types of pain in the clinicalpractice.Furthermore,we discussed possible factors with potential to influence placebo effects in the clinical practice fromseveral perspectives:patients,healthcare workers,and medical environment.And we proposed several strategies to optimizeplacebo effects in the clinical practice from different perspectives.From patients' perspective,they should keep positiveand optimistic attitudes to the medical treatment,with their expectancy for rehabilitation regulated in a median and reason-able level and their negative emotions well controlled.From healthcare workers' perspective,they should be patient-cen-tered,establish a harmonious doctor-patient relationship,and deliver positive expectancy to patients through proper instruc-tions and behaviors.From the medical environment perspective,the multi-dimensional information(e.g.,vision,touch,andtaste) of therapy-related medicine or instruments should be presented to patients,with highlight on their clinical efficacyand value.In the end,we discussed several issues that could hamper the translation of basic research findings relevant toplacebo effects into their clinical applications,and the possible solutions for future studies.
To promote the translation of basic findings into clinical practice and to optimize placebo effect in clinical ap-plications,psychological mechanisms and clinical applications of placebo effects were comprehensively reviewed in thepresent study.We firstly summarized the involvement of expectancy,classical conditioning,social learning,and individualfactors in the generation of placebo effects.The interactions among expectancy,conditioning,motivation(e.g.,desire for re-lief),cognition(e.g.,somatic focus),and individual factors(e.g.,emotional state and personality trait) were highlighted.Then,we discussed evidence demonstrating placebo induced analgesic effects for relieving various types of pain in the clinicalpractice.Furthermore,we discussed possible factors with potential to influence placebo effects in the clinical practice fromseveral perspectives:patients,healthcare workers,and medical environment.And we proposed several strategies to optimizeplacebo effects in the clinical practice from different perspectives.From patients' perspective,they should keep positiveand optimistic attitudes to the medical treatment,with their expectancy for rehabilitation regulated in a median and reason-able level and their negative emotions well controlled.From healthcare workers' perspective,they should be patient-cen-tered,establish a harmonious doctor-patient relationship,and deliver positive expectancy to patients through proper instruc-tions and behaviors.From the medical environment perspective,the multi-dimensional information(e.g.,vision,touch,andtaste) of therapy-related medicine or instruments should be presented to patients,with highlight on their clinical efficacyand value.In the end,we discussed several issues that could hamper the translation of basic research findings relevant toplacebo effects into their clinical applications,and the possible solutions for future studies.
引文
1 Stewart-Williams S,Podd J.The placebo effect:dissolving the expectancy versus conditioning debate.Psychological Bulletin,2004,130(2):324-340
2 Colagiuri B,Schenk LA,Kessler MD,et al.The placebo effect:From concepts to genes.Neuroscience,2015,307:171-190
3 Enck P,Bingel U,Schedlowski M,et al.The placebo resp-onse in medicine:minimize,maximize or personalize?Nat-ure Reviews:Drug Discovery,2013,12(3):191-204
4 Geers AL,Miller FG.Understanding and translating the knowledge about placebo effects:the contribution of psychology.Current Opinion in Psychiatry,2014,27(5):326-3315
5邓潇斐,罗非,郭建友.对立的双生子:基于疼痛的安慰剂效应和反安慰剂效应机制.心理科学进展,2015,23(5):822-835
6 Schedlowski M,Enck P,Rief W,et al.Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses:Implications for Clinical Trials and Clinical Practice.Pharmacological Reviews,2015,67(3):697-730
7 Bingel U,Wanigasekera V,Wiech K,et al.The effect of treatment expectation on drug efficacy:imaging the analgesic benefit of the opioid remifentanil.Science Translational Medicine,2011,3(70):70ra14
8 Zhang RR,Zhang WC,Wang JY,et al.The opioid placebo analgesia is mediated exclusively through mu-opioid receptor in rat.International Journal of Neuropsychopharmacology,2013,16(4):849-856
9 Voudouris NJ,Peck CL,Coleman G.Conditioned placebo responses.Journal of Personality and Social Psychology,1985,48(1):47-53
10 Colloca L,Petrovic P,Wager TD,et al.How the number of learning trials affects placebo and nocebo responses.Pain,2010,151(2):430-439
11 Yeung STA,Colagiuri B,Lovibond PF,et al.Partial reinforcement,extinction,and placebo analgesia.Pain,2014,155(6):1110-1117
12 Colloca L,Benedetti F.Placebo analgesia induced by social observational learning.Pain,2009,144(1):28-34
13 Hunter T,Siess F,Colloca L.Socially induced placebo analgesia:A comparison of a pre-recorded versus live face-toface observation.European Journal of Pain,2014,18(7):914-922
14 Morton DL,Watson A,El-Deredy W,et al.Reproducibility of placebo analgesia:Effect of dispositional optimism.Pain,2009,146(1-2):194-198
15 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
16 Vase L,Robinson ME,Verne GN,et al.Increased placebo analgesia over time in irritable bowel syndrome(IBS)patients is associated with desire and expectation but not endogenous opioid mechanisms.Pain,2005,115(3):338-347
17 Colloca L,Benedetti F.How prior experience shapes placebo analgesia.Pain,2006,124(1):126-133
18 Kessner S,Forkmann K,Ritter C,et al.The effect of treatment history on therapeutic outcome:psychological and neurobiological underpinnings.Plo S One,2014,9(9):e109014
19 Montgomery G,Kirsch I.Classical conditioning and the placebo effect.Pain,1997,72(1):107-113
20 Jensen KB,Kaptchuk TJ,Chen X,et al.A Neural Mechanism for Nonconscious Activation of Conditioned Placebo and Nocebo Responses.Cerebral Cortex,2015,25(10):3903-3910
21 Price DD,Finniss DG,Benedetti F.A Comprehensive Review of the Placebo Effect:Recent Advances and Current Thought.Annual Review of Psychology,2008,59(1):565-590
22 Price DD,Milling LS,Kirsch I,et al.An analysis of factors that contribute to the magnitude of placebo analgesia in an experimental paradigm.Pain,1999,83(2):147-156
23 Geers AL,Helfer SG,Weiland PE,et al.Expectations and placebo response:a laboratory investigation into the role of somatic focus.Journal of Behavioral Medicine,2006,29(2):171-178
24 Geers AL,Wellman JA,Fowler SL,et al.Dispositional optimism predicts placebo analgesia.Journal of Pain,2010,11(11):1165-1171
25 Carlino E,Benedetti F.Different contexts,different pains,different experiences.Neuroscience,2016,338:19-26
26 Linde K,Witt CM,Streng A,et al.The impact of patient expectations on outcomes in four randomized controlled trials of acupuncture in patients with chronic pain.Pain,2007,128(3):264-271
27 Gu AP,Gu CN,Ahmed AT,et al.Sham surgical procedures for pain intervention result in significant improvements in pain:systematic-review and meta-analysis:Metaepidemiologic research requires reporting requirements.Journal of Clinical Epidemiology,2017,87:108
28 Harden RN,Saracoglu M,Connolly S,et al.“Managing”the Placebo Effect:The Single-Blind Placebo Lead-in Response in Two Pain Models.Pain Medicine,2016,17(12):2305-2310
29 Klinger R,Kothe R,Schmitz J,et al.Placebo effects of a sham opioid solution:a randomized controlled study in patients with chronic low back pain.Pain,2017,158(10):1893-1902
30 Carvalho C,Caetano JM,Cunha L,et al.Open-label placebo treatment in chronic low back pain:a randomized controlled trial.Pain,2016,157(12):2766-2772
31 Pollo A,Amanzio M,Arslanian A,et al.Response expectancies in placebo analgesia and their clinical relevance.Pain,2001,93(1):77-84
32 Lidstone SC,Schulzer M,Dinelle K,et al.Effects of expectation on placebo-induced dopamine release in Parkinson disease.Archives of General Psychiatry,2010,67(8):857-865
33 Ruan X,Tran L,Kaye AD.Harnessing positive placebo effect and minimize negative nocebo effect:the art of a healing profession.Pain,2016,157(10):2390
34 Gracely RH,Dubner R,Deeter WR,et al.Clinicians’expectations influence placebo analgesia.Lancet,1985,1(8419):43
35 Czerniak E,Biegon A,Ziv A,et al.Manipulating the Placebo Response in Experimental Pain by Altering Doctor’s Performance Style.Frontiers in Psychology,2016,7:874
36 Kaptchuk TJ,Kelley JM,Conboy LA,et al.Components of placebo effect:randomised controlled trial in patients withirritable bowel syndrome.Deutsche Zeitschrift Für Akupunktur,2008,336(7651):999-1003
37 Ferreira PH,Ferreira ML,Maher CG,et al.The therapeutic alliance between clinicians and patients predicts outcome in chronic low back pain.Physical Therapy,2013,93(4):470-478
38 Levine JD,Gordon NC,Smith R,et al.Analgesic responses to morphine and placebo in individuals with postoperative pain.Pain,1981,10(3):379-389
39 Espay AJ,Norris MM,Eliassen JC,et al.Placebo effect of medication cost in Parkinson disease A randomized double-blind study.Neurology,2015,84(8):794-802
40 Tetreault P,Mansour A,Vachon-Presseau E,et al.Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials.PLo S Biology,2016,14(10):e1002570
41顾丽佳,郭建友.安慰剂镇痛效应的个体差异及其影响因素.中国临床心理学杂志,2014,22(6):994-998
42 Yu R,Gollub RL,Vangel M,et al.Placebo analgesia and reward processing:integrating genetics,personality,and intrinsic brain activity.Human Brain Mapping,2014,35(9):4583-4593
2 Colagiuri B,Schenk LA,Kessler MD,et al.The placebo effect:From concepts to genes.Neuroscience,2015,307:171-190
3 Enck P,Bingel U,Schedlowski M,et al.The placebo resp-onse in medicine:minimize,maximize or personalize?Nat-ure Reviews:Drug Discovery,2013,12(3):191-204
4 Geers AL,Miller FG.Understanding and translating the knowledge about placebo effects:the contribution of psychology.Current Opinion in Psychiatry,2014,27(5):326-3315
5邓潇斐,罗非,郭建友.对立的双生子:基于疼痛的安慰剂效应和反安慰剂效应机制.心理科学进展,2015,23(5):822-835
6 Schedlowski M,Enck P,Rief W,et al.Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses:Implications for Clinical Trials and Clinical Practice.Pharmacological Reviews,2015,67(3):697-730
7 Bingel U,Wanigasekera V,Wiech K,et al.The effect of treatment expectation on drug efficacy:imaging the analgesic benefit of the opioid remifentanil.Science Translational Medicine,2011,3(70):70ra14
8 Zhang RR,Zhang WC,Wang JY,et al.The opioid placebo analgesia is mediated exclusively through mu-opioid receptor in rat.International Journal of Neuropsychopharmacology,2013,16(4):849-856
9 Voudouris NJ,Peck CL,Coleman G.Conditioned placebo responses.Journal of Personality and Social Psychology,1985,48(1):47-53
10 Colloca L,Petrovic P,Wager TD,et al.How the number of learning trials affects placebo and nocebo responses.Pain,2010,151(2):430-439
11 Yeung STA,Colagiuri B,Lovibond PF,et al.Partial reinforcement,extinction,and placebo analgesia.Pain,2014,155(6):1110-1117
12 Colloca L,Benedetti F.Placebo analgesia induced by social observational learning.Pain,2009,144(1):28-34
13 Hunter T,Siess F,Colloca L.Socially induced placebo analgesia:A comparison of a pre-recorded versus live face-toface observation.European Journal of Pain,2014,18(7):914-922
14 Morton DL,Watson A,El-Deredy W,et al.Reproducibility of placebo analgesia:Effect of dispositional optimism.Pain,2009,146(1-2):194-198
15 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
16 Vase L,Robinson ME,Verne GN,et al.Increased placebo analgesia over time in irritable bowel syndrome(IBS)patients is associated with desire and expectation but not endogenous opioid mechanisms.Pain,2005,115(3):338-347
17 Colloca L,Benedetti F.How prior experience shapes placebo analgesia.Pain,2006,124(1):126-133
18 Kessner S,Forkmann K,Ritter C,et al.The effect of treatment history on therapeutic outcome:psychological and neurobiological underpinnings.Plo S One,2014,9(9):e109014
19 Montgomery G,Kirsch I.Classical conditioning and the placebo effect.Pain,1997,72(1):107-113
20 Jensen KB,Kaptchuk TJ,Chen X,et al.A Neural Mechanism for Nonconscious Activation of Conditioned Placebo and Nocebo Responses.Cerebral Cortex,2015,25(10):3903-3910
21 Price DD,Finniss DG,Benedetti F.A Comprehensive Review of the Placebo Effect:Recent Advances and Current Thought.Annual Review of Psychology,2008,59(1):565-590
22 Price DD,Milling LS,Kirsch I,et al.An analysis of factors that contribute to the magnitude of placebo analgesia in an experimental paradigm.Pain,1999,83(2):147-156
23 Geers AL,Helfer SG,Weiland PE,et al.Expectations and placebo response:a laboratory investigation into the role of somatic focus.Journal of Behavioral Medicine,2006,29(2):171-178
24 Geers AL,Wellman JA,Fowler SL,et al.Dispositional optimism predicts placebo analgesia.Journal of Pain,2010,11(11):1165-1171
25 Carlino E,Benedetti F.Different contexts,different pains,different experiences.Neuroscience,2016,338:19-26
26 Linde K,Witt CM,Streng A,et al.The impact of patient expectations on outcomes in four randomized controlled trials of acupuncture in patients with chronic pain.Pain,2007,128(3):264-271
27 Gu AP,Gu CN,Ahmed AT,et al.Sham surgical procedures for pain intervention result in significant improvements in pain:systematic-review and meta-analysis:Metaepidemiologic research requires reporting requirements.Journal of Clinical Epidemiology,2017,87:108
28 Harden RN,Saracoglu M,Connolly S,et al.“Managing”the Placebo Effect:The Single-Blind Placebo Lead-in Response in Two Pain Models.Pain Medicine,2016,17(12):2305-2310
29 Klinger R,Kothe R,Schmitz J,et al.Placebo effects of a sham opioid solution:a randomized controlled study in patients with chronic low back pain.Pain,2017,158(10):1893-1902
30 Carvalho C,Caetano JM,Cunha L,et al.Open-label placebo treatment in chronic low back pain:a randomized controlled trial.Pain,2016,157(12):2766-2772
31 Pollo A,Amanzio M,Arslanian A,et al.Response expectancies in placebo analgesia and their clinical relevance.Pain,2001,93(1):77-84
32 Lidstone SC,Schulzer M,Dinelle K,et al.Effects of expectation on placebo-induced dopamine release in Parkinson disease.Archives of General Psychiatry,2010,67(8):857-865
33 Ruan X,Tran L,Kaye AD.Harnessing positive placebo effect and minimize negative nocebo effect:the art of a healing profession.Pain,2016,157(10):2390
34 Gracely RH,Dubner R,Deeter WR,et al.Clinicians’expectations influence placebo analgesia.Lancet,1985,1(8419):43
35 Czerniak E,Biegon A,Ziv A,et al.Manipulating the Placebo Response in Experimental Pain by Altering Doctor’s Performance Style.Frontiers in Psychology,2016,7:874
36 Kaptchuk TJ,Kelley JM,Conboy LA,et al.Components of placebo effect:randomised controlled trial in patients withirritable bowel syndrome.Deutsche Zeitschrift Für Akupunktur,2008,336(7651):999-1003
37 Ferreira PH,Ferreira ML,Maher CG,et al.The therapeutic alliance between clinicians and patients predicts outcome in chronic low back pain.Physical Therapy,2013,93(4):470-478
38 Levine JD,Gordon NC,Smith R,et al.Analgesic responses to morphine and placebo in individuals with postoperative pain.Pain,1981,10(3):379-389
39 Espay AJ,Norris MM,Eliassen JC,et al.Placebo effect of medication cost in Parkinson disease A randomized double-blind study.Neurology,2015,84(8):794-802
40 Tetreault P,Mansour A,Vachon-Presseau E,et al.Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials.PLo S Biology,2016,14(10):e1002570
41顾丽佳,郭建友.安慰剂镇痛效应的个体差异及其影响因素.中国临床心理学杂志,2014,22(6):994-998
42 Yu R,Gollub RL,Vangel M,et al.Placebo analgesia and reward processing:integrating genetics,personality,and intrinsic brain activity.Human Brain Mapping,2014,35(9):4583-4593