Neuro-bio-behavioral mechanisms of placebo and nocebo responses: Implications for clinical trials and clinical practice

Pharmacological Reviews

Volumn 67, Issue 3, 2015, Pages 697-730

  Schedlowski, Manfred ^a   Enck, Paul ^b   Rief, Winfried ^c   Bingel, Ulrike ^a  

^a UNIVERSITY HOSPITAL ESSEN   (Germany)

^b UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^c PHILIPPS UNIVERSITY MARBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

NEUROTRANSMITTER;

ANALGESIA; ANALGESIC ACTIVITY; ANXIETY DISORDER; AUTONOMIC INNERVATION; BEHAVIOR DISORDER; BEHAVIORAL SCIENCE; BRAIN REGION; CLINICAL PRACTICE; COGNITION; CONDITIONING; DEPRESSION; DISEASE SEVERITY; DOCTOR PATIENT RELATION; DRUG EFFICACY; EMOTION; EXPECTATION; FUNCTIONAL MAGNETIC RESONANCE IMAGING; HABITUATION; HEALTH CARE PERSONNEL; HEALTH CARE SYSTEM; HEART RATE; HUMAN; IMMUNE RESPONSE; IMMUNOSUPPRESSIVE TREATMENT; IRRITABLE COLON; LUNG FUNCTION; NAUSEA; NEUROBIOLOGY; NEUROENDOCRINE SYSTEM; NEUROIMAGING; NEUROPHYSIOLOGY; NOCEBO EFFECT; NONHUMAN; PAIN; PAIN INTENSITY; PARKINSON DISEASE; PERCEPTION; PLACEBO EFFECT; PRIORITY JOURNAL; PSYCHOLOGICAL ASPECT; PSYCHOPHARMACOTHERAPY; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SCHIZOPHRENIA; SLEEP DISORDER; STATE DEPENDENT LEARNING; ANIMAL; BRAIN; CLINICAL TRIAL (TOPIC); MEDICAL RESEARCH; PHYSIOLOGY; PROCEDURES;

ANIMALS; BIOMEDICAL RESEARCH; BRAIN; CLINICAL TRIALS AS TOPIC; COGNITION; HUMANS; NOCEBO EFFECT; PLACEBO EFFECT;

EID: 84953371412     PISSN: 00316997     EISSN: 15210081     Source Type: Journal    
DOI: 10.1124/pr.114.009423     Document Type: Review

References (417)

1. Ader R (1976) Conditioned adrenocortical steroid elevations in the rat. J Comp Physiol Psychol 90:1156–1163.
2. Ader R (2003) Conditioned immunomodulation: research needs and directions. Brain Behav Immun 17 (Suppl 1):S51–S57.
3. Ader R and Cohen N (1982) Behaviorally conditioned immunosuppression and murine systemic lupus erythematosus. Science 215:1534–1536.
4. Ader R, Mercurio MG, Walton J, James D, Davis M, Ojha V, Kimball AB, and Fiorentino D (2010) Conditioned pharmacotherapeutic effects: a preliminary study. Psychosom Med 72:192–197.
5. Agid O, Siu CO, Potkin SG, Kapur S, Watsky E, Vanderburg D, Zipursky RB, and Remington G (2013) Meta-regression analysis of placebo response in antipsychotic trials, 1970-2010. Am J Psychiatry 170:1335–1344.
6. Agras WS, Horne M, and Taylor CB (1982) Expectation and the blood-pressurelowering effects of relaxation. Psychosom Med 44:389–395.
7. Albring A, Wendt L, Benson S, Nissen S, Yavuz Z, Engler H, Witzke O, and Schedlowski M (2014) Preserving learned immunosuppressive placebo response: perspectives for clinical application. Clin Pharmacol Ther 96:247–255.
8. Albring A, Wendt L, Benson S, Witzke O, Kribben A, Engler H, and Schedlowski M (2012) Placebo effects on the immune response in humans: the role of learning and expectation. PLoS ONE 7:e49477.
9. Amanzio M and Benedetti F (1999) Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated specific subsystems. J Neurosci 19:484–494.
10. Amanzio M, Corazzini LL, Vase L, and Benedetti F (2009) A systematic review of adverse events in placebo groups of anti-migraine clinical trials. Pain 146:261–269.
11. Amanzio M, Pollo A, Maggi G, and Benedetti F (2001) Response variability to analgesics: a role for non-specific activation of endogenous opioids. Pain 90: 205–215.
12. Amigo I, Cuesta V, Fernández A, and González A (1993) The effect of verbal instructions on blood pressure measurement. J Hypertens 11:293–296.
13. André-Obadia N, Magnin M, and Garcia-Larrea L (2011) On the importance of placebo timing in rTMS studies for pain relief. Pain 152:1233–1237.
14. Apkarian AV, Bushnell MC, Treede RD, and Zubieta JK (2005) Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 9: 463–484.
15. Arakawa A, Kaneko M, and Narukawa M (2015) An investigation of factors contributing to higher levels of placebo response in clinical trials in neuropathic pain: a systematic review and meta-analysis. Clin Drug Investig 35:67–81.
16. Aslaksen PM, Bystad M, Vambheim SM, and Flaten MA (2011) Gender differences in placebo analgesia: event-related potentials and emotional modulation. Psychosom Med 73:193–199.
17. Aslaksen PM and Flaten MA (2008) The roles of physiological and subjective stress in the effectiveness of a placebo on experimentally induced pain. Psychosom Med 70: 811–818.
18. Aslaksen PM, Myrbakk IN, Høifødt RS, and Flaten MA (2007) The effect of experimenter gender on autonomic and subjective responses to pain stimuli. Pain 129: 260–268.
19. Atlas LY, Whittington RA, Lindquist MA, Wielgosz J, Sonty N, and Wager TD (2012) Dissociable influences of opiates and expectations on pain. J Neurosci 32: 8053–8064.
20. Au Yeung ST, Colagiuri B, Lovibond PF, and Colloca L (2014) Partial reinforcement, extinction, and placebo analgesia. Pain 155:1110–1117.
21. Averbuch M and Katzper M (2001) Gender and the placebo analgesic effect in acute pain. Clin Pharmacol Ther 70:287–291.
22. Aziz Q, Thompson DG, Ng VW, Hamdy S, Sarkar S, Brammer MJ, Bullmore ET, Hobson A, Tracey I, and Gregory L, et al. (2000) Cortical processing of human somatic and visceral sensation. J Neurosci 20:2657–2663.
23. Ballenger JC, Burrows GD, DuPont RL Jr, Lesser IM, Noyes R Jr, Pecknold JC, Rifkin A, and Swinson RP (1988) Alprazolam in panic disorder and agoraphobia: results from a multicenter trial. I. Efficacy in short-term treatment. Arch Gen Psychiatry 45:413–422.
24. Barrett JE, King MG, and Pang G (2000) Conditioning rhinitis in allergic humans. Ann N Y Acad Sci 917:853–859.
25. Barsky AJ, Saintfort R, Rogers MP, and Borus JF (2002) Nonspecific medication side effects and the nocebo phenomenon. JAMA 287:622–627.
26. Batterman RC and Lower WR (1968) Placebo responsiveness—influence of previous therapy. Curr Ther Res Clin Exp 10:136–143.
27. Beck A, Burdett M, and Lewis H (2015) The association between waiting for psychological therapy and therapy outcomes as measured by the CORE-OM. Br J Clin Psychol 54:233–248.
28. Beecher HK (1955) The powerful placebo. J Am Med Assoc 159:1602–1606.
29. Beissner F, Meissner K, Bär KJ, and Napadow V (2013) The autonomic brain: an activation likelihood estimation meta-analysis for central processing of autonomic function. J Neurosci 33:10503–10511.
30. Bélanger L, Vallières A, Ivers H, Moreau V, Lavigne G, and Morin CM (2007) Metaanalysis of sleep changes in control groups of insomnia treatment trials. J Sleep Res 16:77–84.
31. Bello S, Moustgaard H, and Hróbjartsson A (2014) The risk of unblinding was infrequently and incompletely reported in 300 randomized clinical trial publications. J Clin Epidemiol 67:1059–1069.
32. Benedetti F (2014) Placebo effects: from the neurobiological paradigm to translational implications. Neuron 84:623–637.
33. Benedetti F (2008) Placebo Effects: Understanding the Mechanisms in Health and Disease, Oxford University Press, Oxford.
34. Benedetti F (2011) The Patient’s Brain. The Neuroscience behind the Doctor-Patient Relationship, Oxford University Press, Oxford.
35. Benedetti F, Amanzio M, Baldi S, Casadio C, Cavallo A, Mancuso M, Ruffini E, Oliaro A, and Maggi G (1998) The specific effects of prior opioid exposure on placebo analgesia and placebo respiratory depression. Pain 75:313–319.
36. Benedetti F, Amanzio M, Baldi S, Casadio C, and Maggi G (1999) Inducing placebo respiratory depressant responses in humans via opioid receptors. Eur J Neurosci 11:625–631.
37. Benedetti F, Amanzio M, Casadio C, Oliaro A, and Maggi G (1997) Blockade of nocebo hyperalgesia by the cholecystokinin antagonist proglumide. Pain 71:135–140.
38. Benedetti F, Amanzio M, Rosato R, and Blanchard C (2011) Nonopioid placebo analgesia is mediated by CB1 cannabinoid receptors. Nat Med 17:1228–1230.
39. Benedetti F, Arduino C, Costa S, Vighetti S, Tarenzi L, Rainero I, and Asteggiano G (2006) Loss of expectation-related mechanisms in Alzheimer’s disease makes analgesic therapies less effective. Pain 121:133–144.
40. Benedetti F, Colloca L, Torre E, Lanotte M, Melcarne A, Pesare M, Bergamasco B, and Lopiano L (2004) Placebo-responsive Parkinson patients show decreased activity in single neurons of subthalamic nucleus. Nat Neurosci 7:587–588.
41. Benedetti F, Durando J, and Vighetti S (2014) Nocebo and placebo modulation of hypobaric hypoxia headache involves the cyclooxygenase-prostaglandins pathway. Pain 155:921–928.
42. Benedetti F, Lanotte M, Colloca L, Ducati A, Zibetti M, and Lopiano L (2009) Electrophysiological properties of thalamic, subthalamic and nigral neurons during the anti-parkinsonian placebo response. J Physiol 587:3869–3883.
43. Benedetti F, Mayberg HS, Wager TD, Stohler CS, and Zubieta JK (2005) Neurobiological mechanisms of the placebo effect. J Neurosci 25:10390–10402.
44. Benedetti F, Pollo A, Lopiano L, Lanotte M, Vighetti S, and Rainero I (2003) Conscious expectation and unconscious conditioning in analgesic, motor, and hormonal placebo/nocebo responses. J Neurosci 23:4315–4323.
45. Benedetti F, Lanotte M, Lopiano L, and Colloca L (2007) When words are painful: unraveling the mechanisms of the nocebo effect. Neuroscience 147:260–271.
46. Benedetti F, Thoen W, Blanchard C, Vighetti S, and Arduino C (2013) Pain as a reward: changing the meaning of pain from negative to positive co-activates opioid and cannabinoid systems. Pain 154:361–367.
47. Benson S, Kotsis V, Rosenberger C, Bingel U, Forsting M, Schedlowski M, Gizewski ER, and Elsenbruch S (2012) Behavioural and neural correlates of visceral pain sensitivity in healthy men and women: does sex matter? Eur J Pain 16:349–358.
48. Bingel U; Placebo Competence Team (2014) Avoiding nocebo effects to optimize treatment outcome. JAMA 312:693–694.
49. Bingel U, Lorenz J, Schoell E, Weiller C, and Büchel C (2006) Mechanisms of placebo analgesia: rACC recruitment of a subcortical antinociceptive network. Pain 120:8–15.
50. Bingel U, Wanigasekera V, Wiech K, Ni Mhuircheartaigh R, Lee MC, Ploner M, and Tracey I (2011) The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil. Sci Transl Med 3:70ra14.
51. Blom TJ, Mingione CJ, Guerdjikova AI, Keck PE Jr, Welge JA, and McElroy SL (2014) Placebo response in binge eating disorder: a pooled analysis of 10 clinical trials from one research group. Eur Eat Disord Rev 22:140–146.
52. Bodenheimer T (2008) Coordinating care—a perilous journey through the health care system. N Engl J Med 358:1064–1071.
53. Booth RJ, Petrie KJ, and Brook RJ (1995) Conditioning allergic skin responses in humans: a controlled trial. Psychosom Med 57:492–495.
54. Boutron I, Estellat C, Guittet L, Dechartres A, Sackett DL, Hróbjartsson A, and Ravaud P (2006) Methods of blinding in reports of randomized controlled trials assessing pharmacologic treatments: a systematic review. PLoS Med 3:e425.
55. Bovbjerg D, Kim YT, Siskind GW, and Weksler ME (1987) Conditioned suppression of plaque-forming cell responses with cyclophosphamide. The role of taste aversion. Ann N Y Acad Sci 496:588–594.
56. Bovbjerg DH (2003) Conditioning, cancer, and immune regulation. Brain Behav Immun 17 (Suppl 1):S58–S61.
57. Bridge JA, Birmaher B, Iyengar S, Barbe RP, and Brent DA (2009) Placebo response in randomized controlled trials of antidepressants for pediatric major depressive disorder. Am J Psychiatry 166:42–49.
58. Broadbent E, Ellis CJ, Thomas J, Gamble G, and Petrie KJ (2009) Further development of an illness perception intervention for myocardial infarction patients: a randomized controlled trial. J Psychosom Res 67:17–23.
59. Brody H (2008) The Placebo Response, Harper Collins, New York.
60. Buitelaar JK, Sobanski E, Stieglitz RD, Dejonckheere J, Waechter S, and Schäuble B (2012) Predictors of placebo response in adults with attention-deficit/hyperactivity disorder: data from 2 randomized trials of osmotic-release oral system methylphenidate. J Clin Psychiatry 73:1097–1102.
61. Buske-Kirschbaum A, Grota L, Kirschbaum C, Bienen T, Moynihan J, Ader R, Blair ML, Hellhammer DH, and Felten DL (1996) Conditioned increase in peripheral blood mononuclear cell (PBMC) number and corticosterone secretion in the rat. Pharmacol Biochem Behav 55:27–32.
62. Butler C and Steptoe A (1986) Placebo responses: an experimental study of psychophysiological processes in asthmatic volunteers. Br J Clin Psychol 25:173–183.
63. Canning BJ and Fischer A (2001) Neural regulation of airway smooth muscle tone. Respir Physiol 125:113–127.
64. Capurso G, Cocomello L, Benedetto U, Cammà C, and Delle Fave G (2012) Metaanalysis: the placebo rate of abdominal pain remission in clinical trials of chronic pancreatitis. Pancreas 41:1125–1131.
65. Cavanna AE, Strigaro G, and Monaco F (2007) Brain mechanisms underlying the placebo effect in neurological disorders. Funct Neurol 22:89–94.
66. Cho HJ (2005) Reviving the old sermon of medicine with the placebo effect. Rev Bras Psiquiatr 27:336–340.
67. Cho HJ, Hotopf M, and Wessely S (2005) The placebo response in the treatment of chronic fatigue syndrome: a systematic review and meta-analysis. Psychosom Med 67:301–313.
68. Choung RS and Locke GR 3rd (2011) Epidemiology of IBS. Gastroenterol Clin North Am 40:1–10.
69. Cockayne S, Adamson J, Corbacho Martin B, Fairhurst C, Hewitt C, Hicks K, Hull R, Keenan AM, Lamb SE, and Loughrey L, et al.; REFORM study (2014) The REFORM study protocol: a cohort randomised controlled trial of a multifaceted podiatry intervention for the prevention of falls in older people. BMJ Open 4:e006977.
70. Cohen D, Consoli A, Bodeau N, Purper-Ouakil D, Deniau E, Guile JM, and Donnelly C (2010) Predictors of placebo response in randomized controlled trials of psychotropic drugs for children and adolescents with internalizing disorders. J Child Adolesc Psychopharmacol 20:39–47.
71. Colagiuri B, Livesey EJ, and Harris JA (2011) Can expectancies produce placebo effects for implicit learning? Psychon Bull Rev 18:399–405.
72. Colloca L (2014) Placebo, nocebo, and learning mechanisms. Handbook Exp Pharmacol 225:17–35.
73. Colloca L and Benedetti F (2005) Placebos and painkillers: is mind as real as matter? Nat Rev Neurosci 6:545–552.
74. Colloca L and Benedetti F (2009) Placebo analgesia induced by social observational learning. Pain 144:28–34.
75. Colloca L and Finniss D (2012) Nocebo effects, patient-clinician communication, and therapeutic outcomes. JAMA 307:567–568.
76. Colloca L, Lopiano L, Lanotte M, and Benedetti F (2004) Overt versus covert treatment for pain, anxiety, and Parkinson’s disease. Lancet Neurol 3:679–684.
77. Colloca L, Sigaudo M, and Benedetti F (2008) The role of learning in nocebo and placebo effects. Pain 136:211–218.
78. Craggs JG, Price DD, Perlstein WM, Verne GN, and Robinson ME (2008) The dynamic mechanisms of placebo induced analgesia: Evidence of sustained and transient regional involvement. Pain 139:660–669.
79. Craggs JG, Price DD, Verne GN, Perlstein WM, and Robinson MM (2007) Functional brain interactions that serve cognitive-affective processing during pain and placebo analgesia. Neuroimage 38:720–729.
80. Cremonini F, Ziogas DC, Chang HY, Kokkotou E, Kelley JM, Conboy L, Kaptchuk TJ, and Lembo AJ (2010) Meta-analysis: the effects of placebo treatment on gastrooesophageal reflux disease. Aliment Pharmacol Ther 32:29–42.
81. Dager SR, Khan A, Cowley D, Avery DH, Elder J, Roy-Byrne P, and Dunner DL (1990) Characteristics of placebo response during long-term treatment of panic disorder. Psychopharmacol Bull 26:273–278.
82. De Allegri M, Pokhrel S, Becher H, Dong H, Mansmann U, Kouyaté B, Kynast-Wolf G, Gbangou A, Sanon M, and Bridges J, et al. (2008) Step-wedge clusterrandomised community-based trials: an application to the study of the impact of community health insurance. Health Res Policy Syst 6:10.
83. de Craen AJ, Kaptchuk TJ, Tijssen JG, and Kleijnen J (1999a) Placebos and placebo effects in medicine: historical overview. J R Soc Med 92:511–515.
84. de Craen AJ, Moerman DE, Heisterkamp SH, Tytgat GN, Tijssen JG, and Kleijnen J (1999b) Placebo effect in the treatment of duodenal ulcer. Br J Clin Pharmacol 48: 853–860.
85. de la Cruz M, Hui D, Parsons HA, and Bruera E (2010) Placebo and nocebo effects in randomized double-blind clinical trials of agents for the therapy for fatigue in patients with advanced cancer. Cancer 116:766–774.
86. de la Fuente-Fernández R, Ruth TJ, Sossi V, Schulzer M, Calne DB, and Stoessl AJ (2001) Expectation and dopamine release: mechanism of the placebo effect in Parkinson’s disease. Science 293:1164–1166.
87. de la Fuente-Fernández R, Schulzer M, and Stoessl AJ (2004) Placebo mechanisms and reward circuitry: clues from Parkinson’s disease. Biol Psychiatry 56:67–71.
88. De Pascalis V, Chiaradia C, and Carotenuto E (2002) The contribution of suggestibility and expectation to placebo analgesia phenomenon in an experimental setting. Pain 96:393–402.
89. Desai JR, Bowen EA, Danielson MM, Allam RR, and Cantor MN (2013) Creation and implementation of a historical controls database from randomized clinical trials. J Am Med Inform Assoc 20 (e1):e162–e168.
90. Deveugele M, Derese A, van den Brink-Muinen A, Bensing J, and De Maeseneer J (2002) Consultation length in general practice: cross sectional study in six European countries. BMJ 325:472.
91. Diederich NJ and Goetz CG (2008) The placebo treatments in neurosciences: New insights from clinical and neuroimaging studies. Neurology 71:677–684.
92. Diener HC, Dowson AJ, Ferrari M, Nappi G, and Tfelt-Hansen P (1999) Unbalanced randomization influences placebo response: scientific versus ethical issues around the use of placebo in migraine trials. Cephalalgia 19:699–700.
93. Djuri_c VJ, Markovi_c BM, Lazarevi_c M, and Jankovi_c BD (1988) Anaphylactic shockinduced conditioned taste aversion. II. Correlation between taste aversion and indicators of anaphylactic shock. Brain Behav Immun 2:24–31.
94. Doenlen R, Krügel U, Wirth T, Riether C, Engler A, Prager G, Engler H, Schedlowski M, and Pacheco-López G (2011) Electrical activity in rat cortico-limbic structures after single or repeated administration of lipopolysaccharide or staphylococcal enterotoxin B. Proc Biol Sci 278:1864–1872.
95. Doering BK and Rief W (2012) Utilizing placebo mechanisms for dose reduction in pharmacotherapy. Trends Pharmacol Sci 33:165–172.
96. Dunn AG, Mandl KD, Coiera E, and Bourgeois FT (2013) The effects of industry sponsorship on comparator selection in trial registrations for neuropsychiatric conditions in children. PLoS ONE 8:e84951.
97. Dunn LB, Palmer BW, and Keehan M (2006) Understanding of placebo controls among older people with schizophrenia. Schizophr Bull 32:137–146.
98. Dworkin SF, Chen AC, LeResche L, and Clark DW (1983) Cognitive reversal of expected nitrous oxide analgesia for acute pain. Anesth Analg 62:1073–1077.
99. Eden D and Zuk Y (1995) Seasickness as a self-fulfilling prophecy: raising selfefficacy to boost performance at sea. J Appl Psychol 80:628–635.
100. Edward SJ, Stevens AJ, Braunholtz DA, Lilford RJ, and Swift T (2005) The ethics of placebo-controlled trials: a comparison of inert and active placebo controls. World J Surg 29:610–614.
101. Eickhoff SB, Lotze M, Wietek B, Amunts K, Enck P, and Zilles K (2006) Segregation of visceral and somatosensory afferents: an fMRI and cytoarchitectonic mapping study. Neuroimage 31:1004–1014.
102. Eippert F, Bingel U, Schoell ED, Yacubian J, Klinger R, Lorenz J, and Büchel C (2009a) Activation of the opioidergic descending pain control system underlies placebo analgesia. Neuron 63:533–543.
103. Eippert F, Finsterbusch J, Bingel U, and Büchel C (2009b) Direct evidence for spinal cord involvement in placebo analgesia. Science 326:404.
104. Eisenberger NI, Master SL, Inagaki TK, Taylor SE, Shirinyan D, Lieberman MD, and Naliboff BD (2011) Attachment figures activate a safety signal-related neural region and reduce pain experience. Proc Natl Acad Sci USA 108:11721–11726.
105. Elsenbruch S (2011) Abdominal pain in Irritable Bowel Syndrome: a review of putative psychological, neural and neuro-immune mechanisms. Brain Behav Immun 25: 386–394.
106. Elsenbruch S (2014) How positive and negative expectations shape the experience of visceral pain. Handbook Exp Pharmacol 225:97–119.
107. Elsenbruch S, Kotsis V, Benson S, Rosenberger C, Reidick D, Schedlowski M, Bingel U, Theysohn N, Forsting M, and Gizewski ER (2012a) Neural mechanisms mediating the effects of expectation in visceral placebo analgesia: an fMRI study in healthy placebo responders and nonresponders. Pain 153:382–390.
108. Elsenbruch S, Schmid J, Bäsler M, Cesko E, Schedlowski M, and Benson S (2012b) How positive and negative expectations shape the experience of visceral pain: an experimental pilot study in healthy women. Neurogastroenterol Motil 24:914–e460.
109. Elsenbruch S and Enck P (2015) Placebo effects and their determinants in gastrointestinal disorders. Nat Rev Gastroenterol Hepatol, in press.
110. Enck P, Benedetti F, and Schedlowski M (2008) New insights into the placebo and nocebo responses. Neuron 59:195–206.
111. Enck P, Bingel U, Schedlowski M, and Rief W (2013) The placebo response in medicine: minimize, maximize or personalize? Nat Rev Drug Discov 12:191–204.
112. Enck P, Horing B, Weimer K, and Klosterhalfen S (2012) Placebo responses and placebo effects in functional bowel disorders. Eur J Gastroenterol Hepatol 24:1–8.
113. Enck P, Vinson B, Malfertheiner P, Zipfel S, and Klosterhalfen S (2009) The placebo response in functional dyspepsia—reanalysis of trial data. Neurogastroenterol Motil 21:370–377.
114. Espay AJ, Norris MM, Eliassen JC, Dwivedi A, Smith MS, Banks C, Allendorfer JB, Lang AE, Fleck DE, and Linke MJ, et al. (2015) Placebo effect of medication cost in Parkinson disease: a randomized double-blind study. Neurology 84:794–802.
115. Euteneuer F, Mills PJ, Pung MA, Rief W, and Dimsdale JE (2014) Neighborhood problems and nocturnal blood pressure dipping. Health Psychol 33:1366–1372.
116. Exton MS, Elfers A, Jeong WY, Bull DF, Westermann J, and Schedlowski M (2000) Conditioned suppression of contact sensitivity is independent of sympathetic splenic innervation. Am J Physiol Regul Integr Comp Physiol 279:R1310–R1315.
117. Exton MS, Gierse C, Meier B, Mosen M, Xie Y, Frede S, Goebel MU, Limmroth V, and Schedlowski M (2002) Behaviorally conditioned immunosuppression in the rat is regulated via noradrenaline and beta-adrenoceptors. J Neuroimmunol 131: 21–30.
118. Exton MS, Herklotz J, Westermann J, and Schedlowski M (2001) Conditioning in the rat: an in vivo model to investigate the molecular mechanisms and clinical implications of brain-immune communication. Immunol Rev 184:226–235.
119. Exton MS, Schult M, Donath S, Strubel T, Bode U, del Rey A, Westermann J, and Schedlowski M (1999) Conditioned immunosuppression makes subtherapeutic cyclosporin effective via splenic innervation. Am J Physiol 276:R1710–R1717.
120. Exton MS, von Hörsten S, Schult M, Vöge J, Strubel T, Donath S, Steinmüller C, Seeliger H, Nagel E, and Westermann J, et al. (1998) Behaviorally conditioned immunosuppression using cyclosporine A: central nervous system reduces IL-2 production via splenic innervation. J Neuroimmunol 88:182–191.
121. Faasse K, Cundy T, Gamble G, and Petrie KJ (2013) The effect of an apparent change to a branded or generic medication on drug effectiveness and side effects. Psychosom Med 75:90–96.
122. Faasse K, Gamble G, Cundy T, and Petrie KJ (2012) Impact of television coverage on the number and type of symptoms reported during a health scare: a retrospective pre-post observational study. BMJ Open 2:pil:e001607.
123. Faria V, Ahs F, Appel L, Linnman C, Bani M, Bettica P, Pich EM, Wahlstedt K, Fredrikson M, and Furmark T (2014) Amygdala-frontal couplings characterizing SSRI and placebo response in social anxiety disorder. Int J Neuropsychopharmacol 17:1149–1157.
124. Farmer AD, Ban VF, Coen SJ, Sanger GJ, Barker GJ, Gresty MA, Giampietro VP, Williams SC, Webb DL, and Hellström PM, et al. (2015) Visually induced nausea causes characteristic changes in cerebral, autonomic and endocrine function in humans. J Physiol 593:1183–1196.
125. Fehm-Wolfsdorf G, Gnadler M, Kern W, Klosterhalfen W, and Kerner W (1993) Classically conditioned changes of blood glucose level in humans. Physiol Behav 54: 155–160.
126. Feltner D, Hill C, Lenderking W, Williams V, and Morlock R (2009) Development of a patient-reported assessment to identify placebo responders in a generalized anxiety disorder trial. J Psychiatr Res 43:1224–1230.
127. Flaten MA, Aslaksen PM, Lyby PS, and Bjørkedal E (2011) The relation of emotions to placebo responses. Philos Trans R Soc Lond B Biol Sci 366:1818–1827.
128. Ford AC, Marwaha A, Lim A, and Moayyedi P (2010) Systematic review and metaanalysis of the prevalence of irritable bowel syndrome in individuals with dyspepsia. Clin Gastroenterol Hepatol 8:401–409.
129. Ford AC and Moayyedi P (2010) Meta-analysis: factors affecting placebo response rate in the irritable bowel syndrome. Aliment Pharmacol Ther 32:144–158.
130. Fratello F, Curcio G, Ferrara M, Marzano C, Couyoumdjian A, Petrillo G, Bertini M, and De Gennaro L (2005) Can an inert sleeping pill affect sleep? Effects on polysomnographic, behavioral and subjective measures. Psychopharmacology (Berl) 181:761–770.
131. Freeman EW and Rickels K (1999) Characteristics of placebo responses in medical treatment of premenstrual syndrome. Am J Psychiatry 156:1403–1408.
132. Freeman S, Yu R, Egorova N, Chen X, Kirsch I, Claggett B, Kaptchuk TJ, Gollub RL, and Kong J (2015) Distinct neural representations of placebo and nocebo effects. Neuroimage 112:197–207.
133. Freeman TB, Vawter DE, Leaverton PE, Godbold JH, Hauser RA, Goetz CG, and Olanow CW (1999) Use of placebo surgery in controlled trials of a cellularbased therapy for Parkinson’s disease. N Engl J Med 341:988–992.
134. Frisaldi E, Carlino E, Lanotte M, Lopiano L, and Benedetti F (2014) Characterization of the thalamic-subthalamic circuit involved in the placebo response through single-neuron recording in Parkinson patients. Cortex 60:3–9.
135. Fulda KG, Slicho T, and Stoll ST (2007) Patient expectations for placebo treatments commonly used in osteopathic manipulative treatment (OMT) clinical trials: a pilot study. Osteopath Med Prim Care 1:3.
136. Fulda S and Wetter TC (2008) Where dopamine meets opioids: a meta-analysis of the placebo effect in restless legs syndrome treatment studies. Brain 131:902–917.
137. Furmark T, Appel L, Henningsson S, Ahs F, Faria V, Linnman C, Pissiota A, Frans O, Bani M, and Bettica P, et al. (2008) A link between serotonin-related gene polymorphisms, amygdala activity, and placebo-induced relief from social anxiety. J Neurosci 28:13066–13074.
138. Furukawa TA, Noma H, Caldwell DM, Honyashiki M, Shinohara K, Imai H, Chen P, Hunot V, and Churchill R (2014) Waiting list may be a nocebo condition in psychotherapy trials: a contribution from network meta-analysis. Acta Psychiatr Scand 130:181–192.
139. Garcia J, Lasiter PS, Bermudez-Rattoni F, and Deems DA (1985) A general theory of aversion learning. Ann N Y Acad Sci 443:8–21.
140. Gardiner JC, Huebner M, Jetton J, and Bradley CJ (2000) Power and sample assessments for tests of hypotheses on cost-effectiveness ratios. Health Econ 9: 227–234.
141. Gauci M, Husband AJ, Saxarra H, and King MG (1994) Pavlovian conditioning of nasal tryptase release in human subjects with allergic rhinitis. Physiol Behav 55: 823–825.
142. Gay LN and Carliner PE (1949) The prevention and treatment of motion sickness; seasickness. Bull Johns Hopkins Hosp 84:470–490.
143. Geers AL, Wellman JA, Fowler SL, Helfer SG, and France CR (2010) Dispositional optimism predicts placebo analgesia. J Pain 11:1165–1171.
144. Geiger F and Wolfgram L (2013) Overshadowing as prevention of anticipatory nausea and vomiting in pediatric cancer patients: study protocol for a randomized controlled trial. Trials 14:103.
145. Geuter S and Büchel C (2013) Facilitation of pain in the human spinal cord by nocebo treatment. J Neurosci 33:13784–13790.
146. Geuter S, Eippert F, Hindi Attar C, and Büchel C (2013) Cortical and subcortical responses to high and low effective placebo treatments. Neuroimage 67:227–236.
147. Ghanta VK, Hiramoto NS, Solvason HB, Soong SJ, and Hiramoto RN (1990) Conditioning: a new approach to immunotherapy. Cancer Res 50:4295–4299.
148. Ghanta VK, Hiramoto RN, Solvason HB, and Spector NH (1985) Neural and environmental influences on neoplasia and conditioning of NK activity. J Immunol 135 (2, Suppl)848s–852s.
149. Ghanta VK, Miura T, Hiramoto NS, and Hiramoto RN (1988) Augmentation of natural immunity and regulation of tumor growth by conditioning. Ann N Y Acad Sci 521:29–42.
150. Giang DW, Goodman AD, Schiffer RB, Mattson DH, Petrie M, Cohen N, and Ader R (1996) Conditioning of cyclophosphamide-induced leukopenia in humans. J Neuropsychiatry Clin Neurosci 8:194–201.
151. Goebel MU, Hübell D, Kou W, Janssen OE, Katsarava Z, Limmroth V, and Schedlowski M (2005) Behavioral conditioning with interferon beta-1a in humans. Physiol Behav 84:807–814.
152. Goebel MU, Meykadeh N, Kou W, Schedlowski M, and Hengge UR (2008) Behavioral conditioning of antihistamine effects in patients with allergic rhinitis. Psychother Psychosom 77:227–234.
153. Goebel MU, Trebst AE, Steiner J, Xie YF, Exton MS, Frede S, Canbay AE, Michel MC, Heemann U, and Schedlowski M (2002) Behavioral conditioning of immunosuppression is possible in humans. FASEB J 16:1869–1873.
154. Goetz CG, Leurgans S, and Raman R; Parkinson Study Group (2002) Placeboassociated improvements in motor function: comparison of subjective and objective sections of the UPDRS in early Parkinson’s disease. Mov Disord 17:283–288.
155. Goetz CG, Wuu J, McDermott MP, Adler CH, Fahn S, Freed CR, Hauser RA, Olanow WC, Shoulson I, and Tandon PK, et al.; Parkinson Study Group (2008) Placebo response in Parkinson’s disease: comparisons among 11 trials covering medical and surgical interventions. Mov Disord 23:690–699.
156. Gorczynski RM, Macrae S, and Kennedy M (1982) Conditioned immune response associated with allogeneic skin grafts in mice. J Immunol 129:704–709.
157. Grigoleit JS, Kullmann JS, Winkelhaus A, Engler H, Wegner A, Hammes F, Oberbeck R, and Schedlowski M (2012) Single-trial conditioning in a human taste-endotoxin paradigm induces conditioned odor aversion but not cytokine responses. Brain Behav Immun 26:234–238.
158. Grochowicz PM, Schedlowski M, Husband AJ, King MG, Hibberd AD, and Bowen KM (1991) Behavioral conditioning prolongs heart allograft survival in rats. Brain Behav Immun 5:349–356.
159. Gueorguieva R, Mallinckrodt C, and Krystal JH (2011) Trajectories of depression severity in clinical trials of duloxetine: insights into antidepressant and placebo responses. Arch Gen Psychiatry 68:1227–1237.
160. Hadamitzky M, Engler H, and Schedlowski M (2013) Learned immunosuppression: extinction, renewal, and the challenge of reconsolidation. J Neuroimmune Pharmacol 8:180–188.
161. Hall KT, Lembo AJ, Kirsch I, Ziogas DC, Douaiher J, Jensen KB, Conboy LA, Kelley JM, Kokkotou E, and Kaptchuk TJ (2012) Catechol-O-methyltransferase val158- met polymorphism predicts placebo effect in irritable bowel syndrome. PLoS ONE 7:e48135.
162. Harrington A (1999) The Placebo Effect. An Interdisciplinary Exploration, Harvard University Press, Boston, MA.
163. Hashmi JA, Baria AT, Baliki MN, Huang L, Schnitzer TJ, and Apkarian AV (2012) Brain networks predicting placebo analgesia in a clinical trial for chronic back pain. Pain 153:2393–2402.
164. Häuser W, Bartram C, Bartram-Wunn E, and Tölle T (2012) Adverse events attributable to nocebo in randomized controlled drug trials in fibromyalgia syndrome and painful diabetic peripheral neuropathy: systematic review. Clin J Pain 28: 437–451.
165. Häuser W, Bartram-Wunn E, Bartram C, Reinecke H, and Tölle T (2011) Systematic review: Placebo response in drug trials of fibromyalgia syndrome and painful peripheral diabetic neuropathy-magnitude and patient-related predictors. Pain 152:1709–1717.
166. Hida E and Tango T (2011) On the three-arm non-inferiority trial including a placebo with a prespecified margin. Stat Med 30:224–231.
167. Hiramoto RN, Hiramoto NS, Rish ME, Soong SJ, Miller DM, and Ghanta VK (1991) Role of immune cells in the Pavlovian conditioning of specific resistance to cancer. Int J Neurosci 59:101–117.
168. Horing B, Weimer K, Muth ER, and Enck P (2015) Prediction of symptom change in placebo versus no-treatment group in experimentally induced motion sickness. Appl Psychophysiol Biofeedback, in press.
169. Horing B, Weimer K, Muth ER, and Enck P (2014) Prediction of placebo responses: a systematic review of the literature. Front Psychol 5:1079.
170. Horing B, Weimer K, Schrade D, Muth ER, Scisco JL, Enck P, and Klosterhalfen S (2013) Reduction of motion sickness with an enhanced placebo instruction: an experimental study with healthy participants. Psychosom Med 75:497–504.
171. Hróbjartsson A and Gøtzsche PC (2001) Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. N Engl J Med 344:1594–1602.
172. Hróbjartsson A and Gøtzsche PC (2004) Is the placebo powerless? Update of a systematic review with 52 new randomized trials comparing placebo with no treatment. J Intern Med 256:91–100.
173. Hróbjartsson A and Gøtzsche PC (2010) Placebo interventions for all clinical conditions. Cochrane Database Syst Rev (1):CD003974.
174. Hucklebridge F (2002) Behavioral conditioning of the immune system. Int Rev Neurobiol 52:325–351.
175. Huedo-Medina TB, Kirsch I, Middlemass J, Klonizakis M, and Siriwardena AN (2012) Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submitted to the Food and Drug Administration. BMJ 345:e8343.
176. Hunter T, Siess F, and Colloca L (2014) Socially induced placebo analgesia: a comparison of a pre-recorded versus live face-to-face observation. Eur J Pain 18: 914–922.
177. Huppert JD, Schultz LT, Foa EB, Barlow DH, Davidson JR, Gorman JM, Shear MK, Simpson HB, and Woods SW (2004) Differential response to placebo among patients with social phobia, panic disorder, and obsessive-compulsive disorder. Am J Psychiatry 161:1485–1487.
178. Ilnyckyj A, Shanahan F, Anton PA, Cheang M, and Bernstein CN (1997) Quantification of the placebo response in ulcerative colitis. Gastroenterology 112: 1854–1858.
179. Irie M, Maeda M, and Nagata S (2001) Can conditioned histamine release occur under urethane anesthesia in guinea pigs? Physiol Behav 72:567–573.
180. Irie M, Nagata S, and Endo Y (2002) Effect of isolation on classical conditioned histamine release in guinea pigs. Neurosci Res 44:31–35.
181. Irie M, Nagata S, and Endo Y (2004) Diazepam attenuates conditioned histamine release in guinea pigs. Int J Psychophysiol 51:231–238.
182. Isenberg SA, Lehrer PM, and Hochron S (1992a) The effects of suggestion and emotional arousal on pulmonary function in asthma: a review and a hypothesis regarding vagal mediation. Psychosom Med 54:192–216.
183. Isenberg SA, Lehrer PM, and Hochron S (1992b) The effects of suggestion on airways of asthmatic subjects breathing room air as a suggested bronchoconstrictor and bronchodilator. J Psychosom Res 36:769–776.
184. Ivanova A and Tamura RN (2011) A two-way enriched clinical trial design: combining advantages of placebo lead-in and randomized withdrawal. Stat Methods Med Res DOI:10.1177/0962280211431023 [published ahead of print].
185. Jänig W (2006) The integrative action of the autonomic nervous system. Neurobiology of homeostasis, Cambridge University Press, Cambridge
186. Janz LJ, Green-Johnson J, Murray L, Vriend CY, Nance DM, Greenberg AH, and Dyck DG (1996) Pavlovian conditioning of LPS-induced responses: effects on corticosterone, splenic NE, and IL-2 production. Physiol Behav 59:1103–1109.
187. Jones BE (2011) Neurobiology of waking and sleeping, in Handbook of Clinical Neurology (Montagna P and Chokroverty S, ed) pp 131–149, Elsevier, Amsterdam
188. Jones RE, Moes N, Zwickey H, Cunningham CL, Gregory WL, and Oken B (2008) Treatment of experimental autoimmune encephalomyelitis with alpha lipoic acid and associative conditioning. Brain Behav Immun 22:538–543.
189. Jubb J and Bensing JM (2013) The sweetest pill to swallow: how patient neurobiology can be harnessed to maximise placebo effects. Neurosci Biobehav Rev 37: 2709–2720.
190. Jütte R (2014) Hahnemann and placebo. Homeopathy 103:208–212.
191. Jütte R (2013) The early history of the placebo. Complement Ther Med 21:94–97.
192. Kaptchuk TJ (1998) Intentional ignorance: a history of blind assessment and placebo controls in medicine. Bull Hist Med 72:389–433.
193. Kaptchuk TJ (2002) The placebo effect in alternative medicine: can the performance of a healing ritual have clinical significance? Ann Intern Med 136:817–825.
194. Kaptchuk TJ (2011) Placebo studies and ritual theory: a comparative analysis of Navajo, acupuncture and biomedical healing. Philos Trans R Soc Lond B Biol Sci 366:1849–1858.
195. Kaptchuk TJ, Friedlander E, Kelley JM, Sanchez MN, Kokkotou E, Singer JP, Kowalczykowski M, Miller FG, Kirsch I, and Lembo AJ (2010) Placebos without deception: a randomized controlled trial in irritable bowel syndrome. PLoS ONE 5:e15591.
196. Kaptchuk TJ, Kelley JM, Conboy LA, Davis RB, Kerr CE, Jacobson EE, Kirsch I, Schyner RN, Nam BH, and Nguyen LT, et al. (2008a) Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome. BMJ 336: 999–1003.
197. Kaptchuk TJ, Kelley JM, Deykin A, Wayne PM, Lasagna LC, Epstein IO, Kirsch I, and Wechsler ME (2008b) Do “placebo responders” exist? Contemp Clin Trials 29: 587–595.
198. Keltner JR, Furst A, Fan C, Redfern R, Inglis B, and Fields HL (2006) Isolating the modulatory effect of expectation on pain transmission: a functional magnetic resonance imaging study. J Neurosci 26:4437–4443.
199. Kemeny ME, Rosenwasser LJ, Panettieri RA, Rose RM, Berg-Smith SM, and Kline JN (2007) Placebo response in asthma: a robust and objective phenomenon. J Allergy Clin Immunol 119:1375–1381.
200. Kessner S, Forkmann K, Ritter C, Wiech K, Ploner M, and Bingel U (2014) The effect of treatment history on therapeutic outcome: psychological and neurobiological underpinnings. PLoS ONE 9:e109014.
201. Khan A, Kolts RL, Rapaport MH, Krishnan KR, Brodhead AE, and Browns WA (2005) Magnitude of placebo response and drug-placebo differences across psychiatric disorders. Psychol Med 35:743–749.
202. Khan A, Redding N, and Brown WA (2008) The persistence of the placebo response in antidepressant clinical trials. J Psychiatr Res 42:791–796.
203. Kim SE, Kubomoto S, Chua K, Amichai MM, and Pimentel M (2012) “Pre-cebo”: an unrecognized issue in the interpretation of adequate relief during irritable bowel syndrome drug trials. J Clin Gastroenterol 46:686–690.
204. Kingwell K (2014) Schizophrenia drug gets negative results for negative symptoms. Nat Rev Drug Discov 13:244–245.
205. Kinon BJ, Potts AJ, and Watson SB (2011) Placebo response in clinical trials with schizophrenia patients. Curr Opin Psychiatry 24:107–113.
206. Kinreich S, Podlipsky I, Jamshy S, Intrator N, and Hendler T (2014) Neural dynamics necessary and sufficient for transition into pre-sleep induced by EEG neurofeedback. Neuroimage 97:19–28.
207. Kirk JM, Doty P, and De Wit H (1998) Effects of expectancies on subjective responses to oral delta9-tetrahydrocannabinol. Pharmacol Biochem Behav 59:287–293.
208. Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, and Johnson BT (2008) Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med 5:e45.
209. Kirsch I and Sapirstein G (1998) Listening to prozac but hearing placebo: A metaanalysis of antidepressant medication. Prev Treat 1:article 2a.
210. Klosterhalfen S, Kellermann S, Braun S, Kowalski A, Schrauth M, Zipfel S, and Enck P (2009) Gender and the nocebo response following conditioning and expectancy. J Psychosom Res 66:323–328.
211. Klosterhalfen S, Kellermann S, Stockhorst U, Wolf J, Kirschbaum C, Hall G, and Enck P (2005) Latent inhibition of rotation chair-induced nausea in healthy male and female volunteers. Psychosom Med 67:335–340.
212. Klosterhalfen S and Klosterhalfen W (1990) Conditioned cyclosporine effects but not conditioned taste aversion in immunized rats. Behav Neurosci 104:716–724.
213. Klosterhalfen S, Rüttgers A, Krumrey E, Otto B, Stockhorst U, Riepl RL, Probst T, and Enck P (2000) Pavlovian conditioning of taste aversion using a motion sickness paradigm. Psychosom Med 62:671–677.
214. Klosterhalfen W and Klosterhalfen S (1983) Pavlovian conditioning of immunosuppression modifies adjuvant arthritis in rats. Behav Neurosci 97:663–666.
215. Kokkotou E, Conboy LA, Ziogas DC, Quilty MT, Kelley JM, Davis RB, Lembo AJ, and Kaptchuk TJ (2010) Serum correlates of the placebo effect in irritable bowel syndrome. Neurogastroenterol Motil 22:285–e81.
216. Kong J, Gollub RL, Rosman IS, Webb JM, Vangel MG, Kirsch I, and Kaptchuk TJ (2006) Brain activity associated with expectancy-enhanced placebo analgesia as measured by functional magnetic resonance imaging. J Neurosci 26:381–388.
217. Kong J, Jensen K, Loiotile R, Cheetham A, Wey H-Y, Tan Y, Rosen B, Smoller JW, Kaptchuk TJ, and Gollub RL (2013) Functional connectivity of the frontoparietal network predicts cognitive modulation of pain. Pain 154:459–467.
218. Kotsis V, Benson S, Bingel U, Forsting M, Schedlowski M, Gizewski ER, and Elsenbruch S (2012) Perceived treatment group affects behavioral and neural responses to visceral pain in a deceptive placebo study. Neurogastroenterol Motil 24:935–e462.
219. Kowalski A, Rapps N, and Enck P (2006) Functional cortical imaging of nausea and vomiting: a possible approach. Auton Neurosci 129:28–35.
220. Koyama T, McHaffie JG, Laurienti PJ, and Coghill RC (2005) The subjective experience of pain: where expectations become reality. Proc Natl Acad Sci USA 102: 12950–12955.
221. Krogsbøll LT, Hróbjartsson A, and Gøtzsche PC (2009) Spontaneous improvement in randomised clinical trials: meta-analysis of three-armed trials comparing no treatment, placebo and active intervention. BMC Med Res Methodol 9:1.
222. Krummenacher P, Candia V, Folkers G, Schedlowski M, and Schönbächler G (2010) Prefrontal cortex modulates placebo analgesia. Pain 148:368–374.
223. La Mantia L, Eoli M, Salmaggi A, and Milanese C (1996) Does a placebo-effect exist in clinical trials on multiple sclerosis? Review of the literature. Ital J Neurol Sci 17:135–139.
224. Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, and Weinshilboum RM (1996) Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 6:243–250.
225. Lamel SA, Myer KA, Younes N, Zhou JA, Maibach H, and Maibach HI (2012) Placebo response in relation to clinical trial design: a systematic review and meta-analysis of randomized controlled trials for determining biologic efficacy in psoriasis treatment. Arch Dermatol Res 304:707–717.
226. Lee HF, Hsieh JC, Lu CL, Yeh TC, Tu CH, Cheng CM, Niddam DM, Lin HC, Lee FY, and Chang FY (2012) Enhanced affect/cognition-related brain responses during visceral placebo analgesia in irritable bowel syndrome patients. Pain 153: 1301–1310.
227. Leon AC (2012) Challenges in designing comparative-effectiveness trials for antidepressants. Clin Pharmacol Ther 91:165–167.
228. Leucht S, Arbter D, Engel RR, Kissling W, and Davis JM (2009) How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials. Mol Psychiatry 14:429–447.
229. Leucht S, Heres S, and Davis JM (2013) Increasing placebo response in antipsychotic drug trials: let’s stop the vicious circle. Am J Psychiatry 170:1232–1234.
230. Leuchter AF, Cook IA, Witte EA, Morgan M, and Abrams M (2002) Changes in brain function of depressed subjects during treatment with placebo. Am J Psychiatry 159:122–129.
231. Leuchter AF, McCracken JT, Hunter AM, Cook IA, and Alpert JE (2009) Monoamine oxidase a and catechol-o-methyltransferase functional polymorphisms and the placebo response in major depressive disorder. J Clin Psychopharmacol 29: 372–377.
232. Levine JD and Gordon NC (1984) Influence of the method of drug administration on analgesic response. Nature 312:755–756.
233. Levine JD, Gordon NC, and Fields HL (1978) The mechanism of placebo analgesia. Lancet 2:654–657.
234. Levine ME, Stern RM, and Koch KL (2006) The effects of manipulating expectations through placebo and nocebo administration on gastric tachyarrhythmia and motion-induced nausea. Psychosom Med 68:478–486.
235. Lidstone SC, Schulzer M, Dinelle K, Mak E, Sossi V, Ruth TJ, de la Fuente-Fernández R, Phillips AG, and Stoessl AJ (2010) Effects of expectation on placebo-induced dopamine release in Parkinson disease. Arch Gen Psychiatry 67:857–865.
236. Lieberman MD, Jarcho JM, Berman S, Naliboff BD, Suyenobu BY, Mandelkern M, and Mayer EA (2004) The neural correlates of placebo effects: a disruption account. Neuroimage 22:447–455.
237. Linde K, Witt CM, Streng A, Weidenhammer W, Wagenpfeil S, Brinkhaus B, Willich SN, and Melchart D (2007) The impact of patient expectations on outcomes in four randomized controlled trials of acupuncture in patients with chronic pain. Pain 128:264–271.
238. Lipset CH (2014) Engage with research participants about socialmedia. NatMed 20:231.
239. Lo B (2015) Sharing clinical trial data: maximizing benefits, minimizing risk. JAMA 313:793–794.
240. Loebel AD, Hyde TS, and Dunner DL (1986) Early placebo response in anxious and depressed patients. J Clin Psychiatry 47:230–233.
241. Longo DL, Duffey PL, Kopp WC, Heyes MP, Alvord WG, Sharfman WH, Schmidt PJ, Rubinow DR, and Rosenstein DL (1999) Conditioned immune response to interferon-gamma in humans. Clin Immunol 90:173–181.
242. Lovick TA (2008) Pro-nociceptive action of cholecystokinin in the periaqueductal grey: a role in neuropathic and anxiety-induced hyperalgesic states. Neurosci Biobehav Rev 32:852–862.
243. Lu HC, Hsieh JC, Lu CL, Niddam DM, Wu YT, Yeh TC, Cheng CM, Chang FY, and Lee SD (2010) Neuronal correlates in the modulation of placebo analgesia in experimentally-induced esophageal pain: a 3T-fMRI study. Pain 148:75–83.
244. Lui F, Colloca L, Duzzi D, Anchisi D, Benedetti F, and Porro CA (2010) Neural bases of conditioned placebo analgesia. Pain 151:816–824.
245. Luparello T, Lyons HA, Bleecker ER, and McFadden ER Jr (1968) Influences of suggestion on airway reactivity in asthmatic subjects. Psychosom Med 30:819–825.
246. Lyby PS, Aslaksen PM, and Flaten MA (2011) Variability in placebo analgesia and the role of fear of pain—an ERP study. Pain 152:2405–2412.
247. Lyerly SB, Ross S, Krugman AD, and Clyde DJ (1964) Drugs And Placebos: The Effects Of Instructions Upon Performance And Mood Under Amphetamine Sulphate And Chloral Hydrate. J Abnorm Psychol 68:321–327.
248. Macedo A, Farré M, and Baños JE (2006) A meta-analysis of the placebo response in acute migraine and how this response may be influenced by some of the characteristics of clinical trials. Eur J Clin Pharmacol 62:161–172.
249. Machado LA, Kamper SJ, Herbert RD, Maher CG, and McAuley JH (2008) Imperfect placebos are common in low back pain trials: a systematic review of the literature. Eur Spine J 17:889–904.
250. Mallinckrodt CH, Zhang L, Prucka WR, and Millen BA (2010) Signal detection and placebo response in schizophrenia: parallels with depression. Psychopharmacol Bull 43:53–72.
251. Mancini M, Wade AG, Perugi G, Lenox-Smith A, and Schacht A (2014) Impact of patient selection and study characteristics on signal detection in placebo-controlled trials with antidepressants. J Psychiatr Res 51:21–29.
252. Martini M, Lee MC, Valentini E, and Iannetti GD (2015) Intracortical modulation, and not spinal inhibition, mediates placebo analgesia. Eur J Neurosci 41:498–504.
253. Maru_si_c A and Feren_ci_c SF (2013) Adoption of the double dummy trial design to reduce observer bias in testing treatments. J R Soc Med 106:196–198.
254. Mavissakalian M (1988) The placebo effect in agoraphobia—II. J Nerv Ment Dis 176: 446–448.
255. Mayberg HS, Silva JA, Brannan SK, Tekell JL, Mahurin RK, McGinnis S, and Jerabek PA (2002) The functional neuroanatomy of the placebo effect. Am J Psychiatry 159:728–737.
256. McCall WV, D’Agostino R Jr, Rosenquist PB, Kimball J, Boggs N, Lasater B, and Blocker J (2011) Dissection of the factors driving the placebo effect in hypnotic treatment of depressed insomniacs. Sleep Med 12:557–564.
257. Mccall WV, Perlis ML, Tu X, Groman AE, Krystal A, and Walsh JK (2005) A comparison of placebo and no-treatment during a hypnotic clinical trial. Int J Clin Pharmacol Ther 43:355–359.
258. McRae C, Cherin E, Yamazaki TG, Diem G, Vo AH, Russell D, Ellgring JH, Fahn S, Greene P, and Dillon S, et al. (2004) Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial. Arch Gen Psychiatry 61:412–420.
259. Meisel C, Schwab JM, Prass K, Meisel A, and Dirnagl U (2005) Central nervous system injury-induced immune deficiency syndrome. Nat Rev Neurosci 6:775–786.
260. Meissner K (2005) Preferring patient-reported to observer-reported outcomes substantially influences the results of the updated systematic review on placebos by Hróbjartsson and Gøtzsche. J Intern Med 257:394, author reply 395–396.
261. Meissner K (2009) Effects of placebo interventions on gastric motility and general autonomic activity. J Psychosom Res 66:391–398.
262. Meissner K and Ziep D (2011) Organ-specificity of placebo effects on blood pressure. Auton Neurosci 164:62–66.
263. Mellergård M and Rosenberg NK (1990) Patterns of response during placebo treatment of panic disorder. Acta Psychiatr Scand 81:340–344.
264. Metrik J, Rohsenow DJ, Monti PM, McGeary J, Cook TA, de Wit H, Haney M, and Kahler CW (2009) Effectiveness of a marijuana expectancy manipulation: Piloting the balanced-placebo design for marijuana. Exp Clin Psychopharmacol 17: 217–225.
265. Moerman D (2002) Meaning, Medicine and the ’Placebo Effect, Cambridge University Press, Cambridge.
266. Moerman DE (2000) Cultural variations in the placebo effect: ulcers, anxiety, and blood pressure. Med Anthropol Q 14:51–72.
267. Moerman DE and Jonas WB (2002) Deconstructing the placebo effect and finding the meaning response. Ann Intern Med 136:471–476.
268. Moncrieff J, Wessely S, and Hardy R (2004) Active placebos versus antidepressants for depression. Cochrane Database Syst Rev (1):CD003012.
269. Moore RA and Aubin HJ (2012) Do placebo response rates from cessation trials inform on strength of addictions? Int J Environ Res Public Health 9:192–211.
270. Mora MS, Nestoriuc Y, and Rief W (2011) Lessons learned from placebo groups in antidepressant trials. Philos Trans R Soc Lond B Biol Sci 366:1879–1888.
271. Morton DL, Watson A, El-Deredy W, and Jones AK (2009) Reproducibility of placebo analgesia: Effect of dispositional optimism. Pain 146:194–198.
272. Murray D and Stoessl AJ (2013) Mechanisms and therapeutic implications of the placebo effect in neurological and psychiatric conditions. Pharmacol Ther 140: 306–318.
273. Narkus A, Lehnigk U, Haefner D, Klinger R, Pfaar O, and Worm M (2013) The placebo effect in allergen-specific immunotherapy trials. Clin Transl Allergy 3:42.
274. Nestoriuc Y, Orav EJ, Liang MH, Horne R, and Barsky AJ (2010) Prediction of nonspecific side effects in rheumatoid arthritis patients by beliefs about medicines. Arthritis Care Res (Hoboken) 62:791–799.
275. Newcorn JH, Sutton VK, Zhang S, Wilens T, Kratochvil C, Emslie GJ, D’souza DN, Schuh LM, and Allen AJ (2009) Characteristics of placebo responders in pediatric clinical trials of attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 48:1165–1172.
276. Nicholas A, Bailey JV, Stevenson F, and Murray E (2013) The Sexunzipped trial: young people’s views of participating in an online randomized controlled trial. J Med Internet Res 15:e276.
277. Niemi MB, Härting M, Kou W, Del Rey A, Besedovsky HO, Schedlowski M, and Pacheco-López G (2007) Taste-immunosuppression engram: reinforcement and extinction. J Neuroimmunol 188:74–79.
278. Noelpp B and Noelpp-Eschenhagen I (1951a) [Experimental bronchial asthma in guinea pigs, Part I. Methods for objective registration of asthma attacks]. Int Arch Allergy Appl Immunol 2:308–320.
279. Noelpp B and Noelpp-Eschenhagen I (1951b) [Role of conditioned reflex in bronchial asthma; experimental investigation on the pathogenesis of bronchial asthma]. Helv Med Acta 18:142–158.
280. Ober K, Benson S, Vogelsang M, Bylica A, Günther D, Witzke O, Kribben A, Engler H, and Schedlowski M (2012) Plasma noradrenaline and state anxiety levels predict placebo response in learned immunosuppression. Clin Pharmacol Ther 91: 220–226.
281. Ogawa A, Hinotsu S, Urushihara H, and Kawakami K (2011) Night-to-night variability of sleep latency significantly predicts the magnitude of subsequent change in sleep latency during placebo administration. Sleep Med 12:565–571.
282. Pacheco-López G, Doenlen R, Krügel U, Arnold M, Wirth T, Riether C, Engler A, Niemi MB, Christians U, and Engler H, et al. (2013) Neurobehavioural activation during peripheral immunosuppression. Int J Neuropsychopharmacol 16:137–149.
283. Pacheco-López G, Engler H, Niemi MB, and Schedlowski M (2006) Expectations and associations that heal: Immunomodulatory placebo effects and its neurobiology. Brain Behav Immun 20:430–446.
284. Pacheco-López G, Niemi MB, Kou W, Härting M, Del Rey A, Besedovsky HO, and Schedlowski M (2004) Behavioural endocrine immune-conditioned response is induced by taste and superantigen pairing. Neuroscience 129:555–562.
285. Pacheco-López G, Niemi MB, Kou W, Härting M, Fandrey J, and Schedlowski M (2005) Neural substrates for behaviorally conditioned immunosuppression in the rat. J Neurosci 25:2330–2337.
286. Pacheco-López G, Riether C, Doenlen R, Engler H, Niemi MB, Engler A, Kavelaars A, Heijnen CJ, and Schedlowski M (2009) Calcineurin inhibition in splenocytes induced by pavlovian conditioning. FASEB J 23:1161–1167.
287. Palermo-Neto J and Guimarães RK (2000) Pavlovian conditioning of lung anaphylactic response in rats. Life Sci 68:611–623.
288. Papadopoulos D and Mitsikostas DD (2010) Nocebo effects in multiple sclerosis trials: a meta-analysis. Mult Scler 16:816–828.
289. Papakostas GI and Fava M (2009) Does the probability of receiving placebo influence clinical trial outcome? A meta-regression of double-blind, randomized clinical trials in MDD. Eur Neuropsychopharmacol 19:34–40.
290. Peciña M, Azhar H, Love TM, Lu T, Fredrickson BL, Stohler CS, and Zubieta JK (2013a) Personality trait predictors of placebo analgesia and neurobiological correlates. Neuropsychopharmacology 38:639–646.
291. Peciña M, Love T, Stohler CS, Goldman D, and Zubieta JK (2015) Effects of the Mu opioid receptor polymorphism (OPRM1 A118G) on pain regulation, placebo effects and associated personality trait measures. Neuropsychopharmacology 40:957–965.
292. Peciña M, Martínez-Jauand M, Hodgkinson C, Stohler CS, Goldman D, and Zubieta JK (2014) FAAH selectively influences placebo effects. Mol Psychiatry 19:385–391.
293. Peciña M, Stohler CS, and Zubieta JK (2013b) Role of m-opioid system in the formation of memory of placebo responses. Mol Psychiatry 18:135–137.
294. Peciña M and Zubieta JK (2015) Molecular mechanisms of placebo responses in humans. Mol Psychiatry 20:416–423.
295. Pecknold JC, Swinson RP, Kuch K, and Lewis CP (1988) Alprazolam in panic disorder and agoraphobia: results from a multicenter trial. III. Discontinuation effects. Arch Gen Psychiatry 45:429–436.
296. Peeke HV, Dark K, Ellman G, McCurry C, and Salfi M (1987) Prior stress and behaviorally conditioned histamine release. Physiol Behav 39:89–93.
297. Perlis ML, McCall WV, Jungquist CR, Pigeon WR, and Matteson SE (2005) Placebo effects in primary insomnia. Sleep Med Rev 9:381–389.
298. Petrie KJ, Cameron LD, Ellis CJ, Buick D, and Weinman J (2002) Changing illness perceptions after myocardial infarction: an early intervention randomized controlled trial. Psychosom Med 64:580–586.
299. Petrovic P, Kalso E, Petersson KM, and Ingvar M (2002) Placebo and opioid analgesia —imaging a shared neuronal network. Science 295:1737–1740.
300. Piercy MA, Sramek JJ, Kurtz NM, and Cutler NR (1996) Placebo response in anxiety disorders. Ann Pharmacother 30:1013–1019.
301. Ploghaus A, Narain C, Beckmann CF, Clare S, Bantick S, Wise R, Matthews PM, Rawlins JN, and Tracey I (2001) Exacerbation of pain by anxiety is associated with activity in a hippocampal network. J Neurosci 21:9896–9903.
302. Pollo A, Vighetti S, Rainero I, and Benedetti F (2003) Placebo analgesia and the heart. Pain 102:125–133.
303. Preston RA, Materson BJ, Reda DJ, and Williams DW (2000) Placebo-associated blood pressure response and adverse effects in the treatment of hypertension: observations from a Department of Veterans Affairs Cooperative Study. Arch Intern Med 160:1449–1454.
304. Price DD, Craggs J, Verne GN, Perlstein WM, and Robinson ME (2007) Placebo analgesia is accompanied by large reductions in pain-related brain activity in irritable bowel syndrome patients. Pain 127:63–72.
305. Quinn VF and Colagiuri B (2015) Placebo interventions for nausea: a systematic review. Ann Behav Med 49:449–462.
306. Quinn VF, MacDougall HG, and Colagiuri B (2015) Galvanic vestibular stimulation: a new model of placebo-induced nausea. J Psychosom Res 78:484–488.
307. Raicek JE, Stone BH, and Kaptchuk TJ (2012) Placebos in 19th century medicine: a quantitative analysis of the BMJ. BMJ 345:e8326.
308. Ramírez-Amaya V, Alvarez-Borda B, Ormsby CE, Martínez RD, Pérez-Montfort R, and Bermúdez-Rattoni F (1996) Insular cortex lesions impair the acquisition of conditioned immunosuppression. Brain Behav Immun 10:103–114.
309. Reinberg AE, Bicakova-Rocher A, Gorceix A, Ashkenazi IE, and Smolensky MH (1994) Placebo effect on the circadian rhythm period tau of temperature and handgrip strength rhythms: interindividual and gender-related difference. Chronobiol Int 11:45–53.
310. Relton C, Torgerson D, O’Cathain A, and Nicholl J (2010) Rethinking pragmatic randomised controlled trials: introducing the “cohort multiple randomised controlled trial” design. BMJ 340:c1066.
311. Reynaert C, Janne P, Vause M, Zdanowicz N, and Lejeune D (1995) Clinical trials of antidepressants: the hidden face: where locus of control appears to play a key role in depression outcome. Psychopharmacology (Berl) 119:449–454.
312. Rheims S, Cucherat M, Arzimanoglou A, and Ryvlin P (2008) Greater response to placebo in children than in adults: a systematic review and meta-analysis in drugresistant partial epilepsy. PLoS Med 5:e166.
313. Rief W, Avorn J, and Barsky AJ (2006) Medication-attributed adverse effects in placebo groups: implications for assessment of adverse effects. Arch Intern Med 166:155–160.
314. Rief W and Glombiewski JA (2012) The hidden effects of blinded, placebo-controlled randomized trials: an experimental investigation. Pain 153:2473–2477.
315. Rief W, Mills PJ, Ancoli-Israel S, Ziegler MG, Pung MA, and Dimsdale JE (2010) Overnight changes of immune parameters and catecholamines are associated with mood and stress. Psychosom Med 72:755–762.
316. Rief W, Nestoriuc Y, von Lilienfeld-Toal A, Dogan I, Schreiber F, Hofmann SG, Barsky AJ, and Avorn J (2009a) Differences in adverse effect reporting in placebo groups in SSRI and tricyclic antidepressant trials: a systematic review and metaanalysis. Drug Saf 32:1041–1056.
317. Rief W, Nestoriuc Y, Weiss S, Welzel E, Barsky AJ, and Hofmann SG (2009b) Metaanalysis of the placebo response in antidepressant trials. J Affect Disord 118:1–8.
318. Riether C, Doenlen R, Pacheco-López G, Niemi MB, Engler A, Engler H, and Schedlowski M (2008) Behavioural conditioning of immune functions: how the central nervous system controls peripheral immune responses by evoking associative learning processes. Rev Neurosci 19:1–17.
319. Riether C, Kavelaars A, Wirth T, Pacheco-López G, Doenlen R, Willemen H, Heijnen CJ, Schedlowski M, and Engler H (2011) Stimulation of b₂-adrenergic receptors inhibits calcineurin activity in CD4(+) T cells via PKA-AKAP interaction. Brain Behav Immun 25:59–66.
320. Rodriguez-Raecke R, Doganci B, Breimhorst M, Stankewitz A, Büchel C, Birklein F, and May A (2010) Insular cortex activity is associated with effects of negative expectation on nociceptive long-term habituation. J Neurosci 30:11363–11368.
321. Rogev E and Pillar G (2013) Placebo for a single night improves sleep in patients with objective insomnia. Isr Med Assoc J 15:434–438.
322. Rohsenow DJ and Marlatt GA (1981) The balanced placebo design: methodological considerations. Addict Behav 6:107–122.
323. Ronel J, Mehilli J, Ladwig KH, Blättler H, Oversohl N, Byrne RA, Bauer A, Schneider S, Linde K, and Henningsen P, et al. (2011) Effects of verbal suggestion on coronary arteries: results of a randomized controlled experimental investigation during coronary angiography. Am Heart J 162:507–511.
324. Roscoe JA, O’Neill M, Jean-Pierre P, Heckler CE, Kaptchuk TJ, Bushunow P, Shayne M, Huston A, Qazi R, and Smith B (2010) An exploratory study on the effects of an expectancy manipulation on chemotherapy-related nausea. J Pain Symptom Manage 40:379–390.
325. Roudebush RE and Bryant HU (1991) Conditioned immunosuppression of a murine delayed type hypersensitivity response: dissociation from corticosterone elevation. Brain Behav Immun 5:308–317.
326. Rutherford BR, Marcus SM, Wang P, Sneed JR, Pelton G, Devanand D, Duan N, and Roose SP (2013) A randomized, prospective pilot study of patient expectancy and antidepressant outcome. Psychol Med 43:975–982.
327. Rutherford BR, Mori S, Sneed JR, Pimontel MA, and Roose SP (2012) Contribution of spontaneous improvement to placebo response in depression: a meta-analytic review. J Psychiatr Res 46:697–702.
328. Rutherford BR, Pott E, Tandler JM, Wall MM, Roose SP, and Lieberman JA (2014) Placebo response in antipsychotic clinical trials: a meta-analysis. JAMA Psychiatry 71:1409–1421.
329. Rutherford BR, Sneed JR, and Roose SP (2009) Does study design influence outcome? The effects of placebo control and treatment duration in antidepressant trials. Psychother Psychosom 78:172–181.
330. Sabbioni ME, Bovbjerg DH, Mathew S, Sikes C, Lasley B, and Stokes PE (1997) Classically conditioned changes in plasma cortisol levels induced by dexamethasone in healthy men. FASEB J 11:1291–1296.
331. Salamone JD (2000) A critique of recent studies on placebo effects of antidepressants: importance of research on active placebos. Psychopharmacology (Berl) 152:1–6.
332. Schedlowski M and Pacheco-López G (2010) The learned immune response: Pavlov and beyond. Brain Behav Immun 24:176–185.
333. Schmid J, Langhorst J, Gaß F, Theysohn N, Benson S, Engler H, Gizewski ER, Forsting M, and Elsenbruch S (2015) Placebo analgesia in patients with functional and organic abdominal pain: a fMRI study in IBS, UC and healthy volunteers. Gut 64:418–427.
334. Schmid J, Theysohn N, Gaß F, Benson S, Gramsch C, Forsting M, Gizewski ER, and Elsenbruch S (2013) Neural mechanisms mediating positive and negative treatment expectations in visceral pain: a functional magnetic resonance imaging study on placebo and nocebo effects in healthy volunteers. Pain 154: 2372–2380.
335. Schmidt L, Braun EK, Wager TD, and Shohamy D (2014) Mind matters: placebo enhances reward learning in Parkinson’s disease. Nat Neurosci 17:1793–1797.
336. Schneider A, Enck P, Streitberger K, Weiland C, Bagheri S, Witte S, Friederich HC, Herzog W, and Zipfel S (2006) Acupuncture treatment in irritable bowel syndrome. Gut 55:649–654.
337. Schweinhardt P, Kalk N, Wartolowska K, Chessell I, Wordsworth P, and Tracey I (2008) Investigation into the neural correlates of emotional augmentation of clinical pain. Neuroimage 40:759–766.
338. Schweinhardt P, Seminowicz DA, Jaeger E, Duncan GH, and Bushnell MC (2009) The anatomy of the mesolimbic reward system: a link between personality and the placebo analgesic response. J Neurosci 29:4882–4887.
339. Scott DJ, Stohler CS, Egnatuk CM, Wang H, Koeppe RA, and Zubieta JK (2007) Individual differences in reward responding explain placebo-induced expectations and effects. Neuron 55:325–336.
340. Scott DJ, Stohler CS, Egnatuk CM, Wang H, Koeppe RA, and Zubieta JK (2008) Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses. Arch Gen Psychiatry 65:220–231.
341. Shah E, Triantafyllou K, Hana AA, and Pimentel M (2014) Adverse events appear to unblind clinical trials in irritable bowel syndrome. Neurogastroenterol Motil 26: 482–488.
342. Shapiro AK (1964) A Historic and Heuristic Definition of the Placebo. Psychiatry 27: 52–58.
343. Shapiro AK and Shapiro E (2010) The Powerful Placebo: From Ancient Priest to Modern Physician, Johns Hopkins University Press, Baltimore.
344. Shelke AR, Roscoe JA, Morrow GR, Colman LK, Banerjee TK, and Kirshner JJ (2008) Effect of a nausea expectancy manipulation on chemotherapy-induced nausea: a university of Rochester cancer center community clinical oncology program study. J Pain Symptom Manage 35:381–387.
345. Shetty N, Friedman JH, Kieburtz K, Marshall FJ, and Oakes D; Parkinson Study Group (1999) The placebo response in Parkinson’s disease. Clin Neuropharmacol 22:207–212.
346. Sinyor M, Levitt AJ, Cheung AH, Schaffer A, Kiss A, Dowlati Y, and Lanctôt KL (2010) Does inclusion of a placebo arm influence response to active antidepressant treatment in randomized controlled trials? Results from pooled and meta-analyses. J Clin Psychiatry 71:270–279.
347. Smith GR Jr and McDaniel SM (1983) Psychologically mediated effect on the delayed hypersensitivity reaction to tuberculin in humans. Psychosom Med 45:65–70.
348. Spector NH (1996) Neuroimmunomodulation: a brief review. Can conditioning of natural killer cell activity reverse cancer and/or aging? Regul Toxicol Pharmacol 24:S32–S38.
349. Spiro HM (1986) Doctors, Patients and Placebo, Yale University Press, New Haven, CT.
350. Stathis P, Smpiliris M, Konitsiotis S, and Mitsikostas DD (2013) Nocebo as a potential confounding factor in clinical trials for Parkinson’s disease treatment: a meta-analysis. Eur J Neurol 20:527–533.
351. Stein DJ, Baldwin DS, Dolberg OT, Despiegel N, and Bandelow B (2006) Which factors predict placebo response in anxiety disorders and major depression? An analysis of placebo-controlled studies of escitalopram. J Clin Psychiatry 67: 1741–1746.
352. Stein N, Sprenger C, Scholz J, Wiech K, and Bingel U (2012) White matter integrity of the descending pain modulatory system is associated with interindividual differences in placebo analgesia. Pain 153:2210–2217.
353. Stockhorst U, de Fries D, Steingrueber HJ, and Scherbaum WA (2011) Unconditioned and conditioned effects of intranasally administered insulin vs placebo in healthy men: a randomised controlled trial. Diabetologia 54:1502–1506.
354. Stockhorst U, Gritzmann E, Klopp K, Schottenfeld-Naor Y, Hübinger A, Berresheim HW, Steingrüber HJ, and Gries FA (1999) Classical conditioning of insulin effects in healthy humans. Psychosom Med 61:424–435.
355. Stockhorst U, Hall G, Enck P, and Klosterhalfen S (2014) Effects of overshadowing on conditioned and unconditioned nausea in a rotation paradigm with humans. Exp Brain Res 232:2651–2664.
356. Stockhorst U, Mahl N, Krueger M, Huenig A, Schottenfeld-Naor Y, Huebinger A, Berresheim HW, Steingrueber HJ, and Scherbaum WA (2004) Classical conditioning and conditionability of insulin and glucose effects in healthy humans. Physiol Behav 81:375–388.
357. Stockhorst U, Wiener JA, Klosterhalfen S, Klosterhalfen W, Aul C, and Steingrüber HJ (1998) Effects of overshadowing on conditioned nausea in cancer patients: an experimental study. Physiol Behav 64:743–753.
358. Stolberg M (2006) Inventing the randomized double-blind trial: the Nuremberg salt test of 1835. J R Soc Med 99:642–643.
359. Strafella AP, Ko JH, and Monchi O (2006) Therapeutic application of transcranial magnetic stimulation in Parkinson’s disease: the contribution of expectation. Neuroimage 31:1666–1672.
360. Su C, Lichtenstein GR, Krok K, Brensinger CM, and Lewis JD (2004) A metaanalysis of the placebo rates of remission and response in clinical trials of active Crohn’s disease. Gastroenterology 126:1257–1269.
361. Suchman AL and Ader R (1992) Classic conditioning and placebo effects in crossover studies. Clin Pharmacol Ther 52:372–377.
362. Suetsugi M, Mizuki Y, Yamamoto K, Uchida S, and Watanabe Y (2007) The effect of placebo administration on the first-night effect in healthy young volunteers. Prog Neuropsychopharmacol Biol Psychiatry 31:839–847.
363. Summerfield C and de Lange FP (2014) Expectation in perceptual decision making: neural and computational mechanisms. Nat Rev Neurosci 15:745–756.
364. Talley NJ, Locke GR, Lahr BD, Zinsmeister AR, Cohard-Radice M, D’Elia TV, Tack J, and Earnest DL (2006) Predictors of the placebo response in functional dyspepsia. Aliment Pharmacol Ther 23:923–936.
365. Theysohn N, Schmid J, Icenhour A, Mewes C, Forsting M, Gizewski ER, Schedlowski M, Elsenbruch S, and Benson S (2014) Are there sex differences in placebo analgesia during visceral pain processing? A fMRI study in healthy subjects. Neurogastroenterol Motil 26:1743–1753.
366. Thijs L, Amery A, Birkenhäger W, Bulpitt CJ, Clement D, de Leeuw P, De Schaepdryver A, Dollery C, Forette F, and Henry JF, et al. (1990) Age-related effects of placebo and active treatment in patients beyond the age of 60 years: the need for a proper control group. J Hypertens 8:997–1002.
367. Thompson WG (2005) The Placebo Effect and Health: Combining Science and Compassionate Care, Prometheus Books, Amherst, NY.
368. Tracey I (2010a) Getting the pain you expect: mechanisms of placebo, nocebo and reappraisal effects in humans. Nat Med 16:1277–1283.
369. Tracey I and Mantyh PW (2007) The cerebral signature for pain perception and its modulation. Neuron 55:377–391.
370. Tracey KJ (2009) Reflex control of immunity. Nat Rev Immunol 9:418–428.
371. Tracey KJ (2010b) Understanding immunity requires more than immunology. Nat Immunol 11:561–564.
372. Tudur Smith C, Dwan K, Altman DG, Clarke M, Riley R, and Williamson PR (2014) Sharing individual participant data from clinical trials: an opinion survey regarding the establishment of a central repository. PLoS ONE 9:e97886.
373. Turnbull JW (1962) Asthma conceived as a learned response. J Psychosom Res 6: 59–70.
374. Vase L, Robinson ME, Verne GN, and Price DD (2003) The contributions of suggestion, desire, and expectation to placebo effects in irritable bowel syndrome patients. An empirical investigation. Pain 105:17–25.
375. Vase L, Robinson ME, Verne GN, and Price DD (2005) Increased placebo analgesia over time in irritable bowel syndrome (IBS) patients is associated with desire and expectation but not endogenous opioid mechanisms. Pain 115:338–347.
376. Vits S, Cesko E, Benson S, Rueckert A, Hillen U, Schadendorf D, and Schedlowski M (2013) Cognitive factors mediate placebo responses in patients with house dust mite allergy. PLoS ONE 8:e79576.
377. Vits S, Cesko E, Enck P, Hillen U, Schadendorf D, and Schedlowski M (2011) Behavioural conditioning as the mediator of placebo responses in the immune system. Philos Trans R Soc Lond B Biol Sci 366:1799–1807.
378. Vögtle E, Barke A, and Kröner-Herwig B (2013) Nocebo hyperalgesia induced by social observational learning. Pain 154:1427–1433.
379. Volkow ND, Wang GJ, Ma Y, Fowler JS, Zhu W, Maynard L, Telang F, Vaska P, Ding YS, and Wong C, et al. (2003) Expectation enhances the regional brain metabolic and the reinforcing effects of stimulants in cocaine abusers. J Neurosci 23: 11461–11468.
380. von Hörsten S, Exton MS, Vöge J, Schult M, Nagel E, Schmidt RE, Westermann J, and Schedlowski M (1998) Cyclosporine A affects open field behavior in DA rats. Pharmacol Biochem Behav 60:71–76.
381. Waber RL, Shiv B, Carmon Z, and Ariely D (2008) Commercial features of placebo and therapeutic efficacy. JAMA 299:1016–1017.
382. Wager TD, Atlas LY, Leotti LA, and Rilling JK (2011) Predicting individual differences in placebo analgesia: contributions of brain activity during anticipation and pain experience. J Neurosci 31:439–452.
383. Wager TD, Matre D, and Casey KL (2006) Placebo effects in laser-evoked pain potentials. Brain Behav Immun 20:219–230.
384. Wager TD, Rilling JK, Smith EE, Sokolik A, Casey KL, Davidson RJ, Kosslyn SM, Rose RM, and Cohen JD (2004) Placebo-induced changes in FMRI in the anticipation and experience of pain. Science 303:1162–1167.
385. Wager TD, Scott DJ, and Zubieta JK (2007) Placebo effects on human mu-opioid activity during pain. Proc Natl Acad Sci USA 104:11056–11061.
386. Walsh BT, Seidman SN, Sysko R, and Gould M (2002) Placebo response in studies of major depression: variable, substantial, and growing. JAMA 287:1840–1847.
387. Wang X, Shang D, Ribbing J, Ren Y, Deng C, Zhou T, Guo F, and LuW(2012) Placebo effect model in asthma clinical studies: longitudinal meta-analysis of forced expiratory volume in 1 second. Eur J Clin Pharmacol 68:1157–1166.
388. Watson A, El-Deredy W, Vogt BA, and Jones AK (2007) Placebo analgesia is not due to compliance or habituation: EEG and behavioural evidence. Neuroreport 18: 771–775.
389. Weber FD, Wang J-Y, Born J, and Inostroza M (2014) Sleep benefits in parallel implicit and explicit measures of episodic memory. Learn Mem 21:190–198.
390. Weber MA (2008) Using placebo in hypertension clinical trials: new information and new opportunities. J Hum Hypertens 22:653–655.
391. Wechsler ME, Kelley JM, Boyd IO, Dutile S, Marigowda G, Kirsch I, Israel E, and Kaptchuk TJ (2011) Active albuterol or placebo, sham acupuncture, or no intervention in asthma. N Engl J Med 365:119–126.
392. Weimer K, Colloca L, and Enck P (2015a) Age and sex as moderators of the placebo response – an evaluation of systematic reviews and meta-analyses across medicine. Gerontology 61:97–108.
393. Weimer K, Colloca L, and Enck P (2015b) Placebo effects in psychiatry: mediators and moderators. Lancet Psychiatry 2:246–257.
394. Weimer K and Enck P (2014) Traditional and innovative experimental and clinical trial designs and their advantages and pitfalls. Handbook Exp Pharmacol 225: 237–272.
395. Weimer K, Gulewitsch MD, Schlarb AA, Schwille-Kiuntke J, Klosterhalfen S, and Enck P (2013a) Placebo effects in children: a review. Pediatr Res 74:96–102.
396. Weimer K, Horing B, Stürmer J, Klosterhalfen S, Zipfel S, and Enck P (2013b) Nicotine stimulus expectancy differentially affects reaction time in healthy nonsmokers and smokers depending on sex: a pilot study. Exp Clin Psychopharmacol 21:181–187.
397. Weimer K, Schulte J, Maichle A, Muth ER, Scisco JL, Horing B, Enck P, and Klosterhalfen S (2012) Effects of ginger and expectations on symptoms of nausea in a balanced placebo design. PLoS ONE 7:e49031.
398. Wendt L, Albring A, Benson S, Engler H, Engler A, Hinney A, Rief W, Witzke O, and Schedlowski M (2014a) Catechol-O-methyltransferase Val158Met polymorphism is associated with somatosensory amplification and nocebo responses. PLoS ONE 9:e107665.
399. Wendt L, Albring A, and Schedlowski M (2014b) Learned placebo responses in neuroendocrine and immune functions. Handbook Exp Pharmacol 225:159–181.
400. Wernicke JF and Ossanna MJ (2010) The placebo response in pain and depression: in search of a common pathway. Front Biosci (Schol Ed) 2:106–111.
401. Schol Ed., Whalley B, Hyland ME, and Kirsch I (2008) Consistency of the placebo effect. J Psychosom Res 64:537–541.
402. Wichers MC, Barge-Schaapveld DQ, Nicolson NA, Peeters F, de Vries M, Mengelers R, and van Os J (2009) Reduced stress-sensitivity or increased reward experience: the psychological mechanism of response to antidepressant medication. Neuropsychopharmacology 34:923–931.
403. Williamson MJ, Thomas MJ, and Stern RM (2004) The contribution of expectations to motion sickness symptoms and gastric activity. J Psychosom Res 56:721–726.
404. Winkler A and Rief W (2015) Effect of placebo conditions on polysomnographic parameters in primary insomnia: a meta-analysis. Sleep 38:925–931.
405. Wirth T, Ober K, Prager G, Vogelsang M, Benson S, Witzke O, Kribben A, Engler H, and Schedlowski M (2011) Repeated recall of learned immunosuppression: evidence from rats and men. Brain Behav Immun 25:1444–1451.
406. Wolf S (1950) Effects of suggestion and conditioning on the action of chemical agents in human subjects; the pharmacology of placebos. J Clin Invest 29:100–109.
407. Wolf S (1959) The pharmacology of placebos. Pharmacol Rev 11:689–704.
408. Woodman CL, Noyes R Jr, Ballenger JC, Lydiard RB, Sievers G, and Mihalko D (1994) Predictors of response to alprazolam and placebo in patients with panic disorder. J Affect Disord 30:5–13.
409. Woods SW, Gueorguieva RV, Baker CB, and Makuch RW (2005) Control group bias in randomized atypical antipsychotic medication trials for schizophrenia. Arch Gen Psychiatry 62:961–970.
410. World Medical Association (2013) World Medical Association Declaration of Helsinki: ethical principles formedical research involving human subjects. JAMA 310:2191–2194.
411. Wrobel N, Wiech K, Forkmann K, Ritter C, and Bingel U (2014) Haloperidol blocks dorsal striatum activity but not analgesia in a placebo paradigm. Cortex 57:60–73.
412. Yildiz A, Vieta E, Tohen M, and Baldessarini RJ (2011) Factors modifying drug and placebo responses in randomized trials for bipolar mania. Int J Neuropsychopharmacol 14:863–875.
413. Zelen M (1979) A new design for randomized clinical trials. NEngl JMed 300:1242–1245.
414. Zhang W, Qin S, Guo J, and Luo J (2011) A follow-up fMRI study of a transferable placebo anxiolytic effect. Psychophysiology 48:1119–1128.
415. Zhou Q and Verne GN (2014) Neurogastroenterology: Neuronal correlates of placebo in chronic FGIDs. Nat Rev Gastroenterol Hepatol 11:460–461.
416. Zimmermann-Viehoff F, Meissner K, Koch J, Weber CS, Richter S, and Deter HC (2013) Autonomic effects of suggestive placebo interventions to increase or decrease blood pressure: a randomized controlled trial in healthy subjects. J Psychosom Res 75:32–35.
417. Zubieta JK, Bueller JA, Jackson LR, Scott DJ, Xu Y, Koeppe RA, Nichols TE, and Stohler CS (2005) Placebo effects mediated by endogenous opioid activity on mu-opioid receptors. J Neurosci 25:7754–7762.