Placebo and nocebo responses in drug trials of epilepsy

Epilepsy and Behavior

Volumn 43, Issue , 2015, Pages 128-134

  Zaccara, Gaetano ^a   Giovannelli, Fabio ^a,b   Schmidt, Dieter ^c  

^a Florence Health Authority   (Italy)

^b UNIVERSITY OF FLORENCE   (Italy)

^c Epilepsy Research Group   (Germany)

Author keywords

Adverse effects; Antiepileptic drugs; Meta regression; Nocebo effects; Placebo effects; Side effects

Indexed keywords

ANTICONVULSIVE AGENT; PLACEBO;

ADVERSE DRUG REACTION; ANTICONVULSANT THERAPY; ANXIETY; CLINICAL PRACTICE; COMPARATIVE STUDY; CONTROLLED CLINICAL TRIAL (TOPIC); FOCAL EPILEPSY; HUMAN; META ANALYSIS (TOPIC); NOCEBO EFFECT; PLACEBO EFFECT; REVIEW; TRANSCRANIAL MAGNETIC STIMULATION; CLINICAL TRIAL (TOPIC); EPILEPSY; METHODOLOGY;

ANTICONVULSANTS; CLINICAL TRIALS AS TOPIC; EPILEPSY; HUMANS; NOCEBO EFFECT; PLACEBO EFFECT; RESEARCH DESIGN;

EID: 84923772116     PISSN: 15255050     EISSN: 15255069     Source Type: Journal    
DOI: 10.1016/j.yebeh.2014.12.004     Document Type: Review

References (82)

1. Murray D., Stoessl A.J. Mechanisms and therapeutic implications of the placebo effect in neurological and psychiatric conditions. Pharmacol Ther 2013, 140:306-318.
2. Sullivan R., Behncke I., Purushotham A. Why do we love medicines so much? An evolutionary perspective on the human love of pills, potions and placebo. EMBO Rep 2010, 11:572-578.
3. Finniss D.G., Kaptchuk T.J., Miller F., Benedetti F. Placebo effects: biological, clinical and ethical advances. Lancet 2010, 375:686-695.
4. Tavel M.E. The placebo effect: the good, the bad, and the ugly. Am J Med 2014, 127:484-488.
5. Häuser W., Hansen E., Enck P. Nocebo phenomena in medicine: their relevance in everyday clinical practice. Dtsch Arztebl Int 2012, 109:459-465.
6. Annoni M. Highlights from the 2013 Science of Placebo thematic workshop. eCancer 2013, 7:346.
7. Enck P., Klosterhalfen S., Weimer K., Horing B., Zipfel S. The placebo response in clinical trials: more questions than answers. Philos Trans R Soc Lond B Biol Sci 2011, 366:1889-1895.
8. Rheims S., Cucherat M., Arzimanoglou A., Ryvlin P. Greater response to placebo in children than in adults: a systematic review and meta-analysis in drug-resistant partial epilepsy. PLoS Med 2008, 5:e166.
9. Guekht A.B., Korczyn A.D., Bondareva I.B., Gusev E.I. Placebo responses in randomized trials of antiepileptic drugs. Epilepsy Behav 2010, 17:64-69.
10. Zaccara G., Giovannelli F., Cincotta M., Loiacono G., Verrotti A. Adverse events of placebo-treated, drug-resistant, focal epileptic patients in randomized controlled trials: a systematic review. J Neurol 2014 Jun 11, [Epub ahead of print].
11. Bae E.H., Theodore W.H., Fregni F., Cantello R., Pascual-Leone A., Rotenberg A. An estimate of placebo effect of repetitive transcranial magnetic stimulation in epilepsy. Epilepsy Behav 2011, 20:355-359.
12. Rheims S., Perucca E., Cucherat M., Ryvlin P. Factors determining response to antiepileptic drugs in randomized controlled trials. A systematic review and meta-analysis. Epilepsia 2011, 52:219-233.
13. Halford J.J., Ben-Menachem E., Kwan P., Ness S., Schmitt J., Eerdekens M., et al. A randomized, double-blind, placebo controlled study of the efficacy, safety, and tolerability of adjunctive carisbamate treatment in patients with partial-onset seizures. Epilepsia 2011, 52:816-825.
14. Schmidt D., Beyenburg S., D'Souza J., Stavem K. Clinical features associated with placebo response in refractory focal epilepsy. Epilepsy Behav 2013, 27:393-398.
15. Sillanpää M., Schmidt D. Early seizure frequency and aetiology predict long-term medical outcome in childhood-onset epilepsy. Brain 2009, 132:989-998.
16. French J.A., Krauss G.L., Biton V., Squillacote D., Yang H., Laurenza A., et al. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology 2012, 79:589-596.
17. Emslie G.J., Rush A.J., Weinberg W.A., Kowatch R.A., Hughes C.W., Carmody T., et al. A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry 1997, 54:1031-1037.
18. Lewis D.W., Winner P., Wasiewski W. The placebo responder rate in children and adolescents. Headache 2005, 45:232-239.
19. Rothner A.D., Wasiewski W., Winner P., Lewis D., Stankowski J. Zolmitriptan oral tablet in migraine treatment: high placebo responses in adolescents. Headache 2006, 46:101-109.
20. Fernandes R., Ferreira J.J., Sampaio C. The placebo response in studies of acute migraine. J Pediatr 2008, 152:527-533.
21. Zaccara G., Giovannelli F., Franco V., Cincotta M., Tramacere L., Verrotti A. Adverse events, placebo and nocebo effects in placebo-treated paediatric patients with refractory focal epilepsies. Analysis of double-blind studies. Epilepsy Res 2014, [pii: S0920-1211(14)00248-4]. 10.1016/j.eplepsyres.2014.09.015.
22. Hróbjartsson A., Gøtzsche P.C. Placebo interventions for all clinical conditions. Cochrane Database Syst Rev 2010, (1):CD003974.
23. Kirsch I., Deacon B.J., Huedo-Medina T.B., Scoboria A., Moore T.J., Johnson B.T. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med 2008, 5(2):e45.
24. Häuser W., Bartram-Wunn E., Bartram C., Reinecke H., Tölle T. Systematic review: placebo response in drug trials of fibromyalgia syndrome and painful peripheral diabetic neuropathy - magnitude and patient-related predictors. Pain 2011, 152:1709-1717.
25. Fulda S., Wetter T.C. Where dopamine meets opioids: a meta-analysis of the placebo effect in restless legs syndrome treatment studies. Brain 2008, 131:902-917.
26. Finniss D.G., Kaptchuk T.J., Miller F., Benedetti F. Biological, clinical, and ethical advances of placebo effects. Lancet 2010, 375(9715):686-695.
27. Benedetti F., Carlino E., Pollo A. How placebos change the patient's brain. Neuropsychopharmacology 2011, 36:339-354.
28. Benedetti F., Amanzio M. The placebo response: how words and rituals change the patient's brain. Patient Educ Couns 2011, 84:413-419.
29. Haake M., Müller H.H., Schade-Brittinger C., Basler H.D., Schäfer H., Maier C., et al. German Acupuncture Trials (GERAC) for chronic low back pain: randomized, multicenter, blinded, parallel-group trial with 3 groups. Arch Intern Med 2007, 167:1892-1898.
30. de la Fuente-Fernández R., Ruth T.J., Sossi V., Schulzer M., Calne D.B., Stoessl A.J. Expectation and dopamine release: mechanism of the placebo effect in Parkinson's disease. Science 2001, 293:1164-1166.
31. Benedetti F., Colloca L., Torre E., Lanotte M., Melcarne A., Pesare M., et al. Placebo-responsive Parkinson patients show decreased activity in single neurons of subthalamic nucleus. Nat Neurosci 2004, 7:587-588.
32. Benedetti F., Lanotte M., Colloca L., Ducati A., Zibetti M., Lopiano L. Electrophysiological properties of thalamic, subthalamic and nigral neurons during the anti-parkinsonian placebo response. J Physiol 2009, 587:3869-3883.
33. Wechsler M.E., Kelley J.M., Boyd I.O., Dutile S., Marigowda G., Kirsch I., et al. Active albuterol or placebo, sham acupuncture, or no intervention in asthma. N Engl J Med 2011, 365:119-126.
34. Petrovic P., Dietrich T., Fransson P., Andersson J., Carlsson K., Ingvar M. Placebo in emotional processing-induced expectations of anxiety relief activate a generalized modulatory network. Neuron 2005, 46:957-969.
35. Schoenbaum G., Roesch M. Orbitofrontal cortex, associative learning, and expectancies. Neuron 2005, 47:633-663.
36. Seymour B., O'Doherty J.P., Koltzenburg M., Wiech K., Frackowiak R., Friston K., et al. Opponent appetitive-aversive neural processes underlie predictive learning of pain relief. Nat Neurosci 2005, 8:1234-1240.
37. Bozzi Y., Borrelli E. The role of dopamine signaling in epileptogenesis. Front Cell Neurosci 2013, 17:157.
38. Kovac S., Walker M.C. Neuropeptides in epilepsy. Neuropeptides 2013, 47:467-475.
39. Abhishek A., Doherty M. Mechanisms of the placebo response in pain in osteoarthritis. Osteoarthritis Cartilage 2013, 21:1229-1235.
40. Amanzio M., Benedetti F. Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated specific subsystems. J Neurosci 1999, 19:484-494.
41. Sillanpää M., Schmidt D. Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study. Brain 2006, 129:617-624.
42. Brodie M.J., Barry S.J., Bamagous G.A., Norrie J.D., Kwan P. Patterns of treatment response in newly diagnosed epilepsy. Neurology 2012, 78:1548-1554.
43. Krämer G. The enigma of placebo effects in drug-refractory epilepsies. Epilepsia 2013, 54(Suppl. 2):13-15.
44. Mark J., Cook M.J., O'Brien T.J., Berkovic S.F., Murphy M., Morokoff A., et al. Prediction of seizure likelihood with a long-term, implanted seizure advisory system in patients with drug-resistant epilepsy: a first-in-man study. Lancet Neurol 2013, 12:563-571.
45. Muñana K.R., Zhang D., Patterson E.E. Placebo effect in canine epilepsy trials. J Vet Intern Med 2010, 24:166-170.
46. Muñana K.R., Thomas W.B., Inzana K.D., Nettifee-Osborne J.A., McLucas K.J., Olby N.J., et al. Evaluation of levetiracetam as adjunctive treatment for refractory canine epilepsy: a randomized, placebo-controlled, crossover trial. J Vet Intern Med 2012, 26:341-348.
47. Hirst J.A., Howick J., Aronson J.K., Roberts N., Koshiaris C., Heneghan C. The need for randomization in animal trials: an overview of systematic reviews. PLoS One 2014, 9:e98856.
48. Guite J.W., Logan D.E., McCue R., Sherry D.D., Rose J.B. Parental beliefs and worries regarding adolescent chronic pain. Clin J Pain 2009, 25:223-232.
49. Weimer K., Gulewitsch M.D., Schlarb A.A., Schwille-Kiuntke J., Klosterhalfen S., Enck P. Placebo effects in children: a review. Pediatr Res 2013, 74:96-102.
50. Rief W., Nestoriuc Y., Weiss S., Welzel E., Barsky A.J., Hofmann S.G. Meta-analysis of the placebo response in antidepressant trials. J Affect Disord 2009, 118:1-8.
51. Perucca P., Gilliam F.G. Adverse effects of antiepileptic drugs. Lancet Neurol 2012, 11:792-802.
52. Gilliam F.G., Fessler A.J., Baker G., Vahle V., Carter J., Attarian H. Systematic screening allows reduction of adverse antiepileptic drug effects: a randomized trial. Neurology 2004, 62:23-27.
53. Perucca P., Carter J., Vahle V., Gilliam F.G. Adverse antiepileptic drug effects: toward a clinically and neurobiologically relevant taxonomy. Neurology 2009, 72:1223-1229.
54. Kanner A.M., Barry J.J., Gilliam F., Hermann B., Meador K.J. Depressive and anxiety disorders in epilepsy: do they differ in their potential to worsen common antiepileptic drug-related adverse events?. Epilepsia 2012, 53:1104-1108.
55. Baker G.A., Camfield C., Camfield P., Cramer J.A., Elger C.E., Johnson A.L., et al. Commission on outcome measurement in epilepsy, 1994-1997: final report. Epilepsia 1998, 39:213-231.
56. Carreño M., Gil-Nagel A., Sánchez J.C., Elices E., Serratosa J.M., Salas-Puig J., et al. Strategies to detect adverse effects of antiepileptic drugs in clinical practice. Epilepsy Behav 2008, 13:178-183.
57. Canevini M.P., De Sarro G., Galimberti C.A., Gatti G., Licchetta L., Malerba A., et al. Relationship between adverse effects of antiepileptic drugs, number of coprescribed drugs, and drug load in a large cohort of consecutive patients with drug-refractory epilepsy. Epilepsia 2010, 51:797-804.
58. Giovannelli F., Zaccara G., Cincotta M., Loiacono G., Verrotti A. Characterization of the adverse events profile of placebo-treated patients in randomized controlled trials on drug-resistant focal epilepsies. J Neurol 2014 Oct 14, [Epub ahead of print].
59. Flaten M.A., Simonsen T., Olsen H. Drug-related information generates placebo and nocebo responses that modify the drug response. Psychosom Med 1999, 61:250-255.
60. Liccardi G., Senna G., Russo M., Bonadonna P., Crivellaro M., Dama A., et al. Evaluation of the nocebo effect during oral challenge in patients with adverse drug reactions. J Investig Allergol Clin Immunol 2004, 14:104-107.
61. Levine M.E., Stern R.M., Koch K.L. The effects of manipulating expectations through placebo and nocebo administration on gastric tachyarrhythmia and motion-induced nausea. Psychosom Med 2006, 68:478-486.
62. Colloca L., Miller F.G. The nocebo effect and its relevance for clinical practice. Psychosom Med 2011, 73:598-603.
63. Amanzio M., Corazzini L.L., Vase L., Benedetti F. A systematic review of adverse events in placebo groups of anti-migraine clinical trials. Pain 2009, 146:261-269.
64. Benedetti F., Amanzio M. Mechanisms of the placebo response. Pulm Pharmacol Ther 2013, 26:520-523.
65. Mitsikostas D.D., Mantonakis L.I., Chalarakis N.G. Nocebo is the enemy, not placebo. A meta-analysis of reported side effects after placebo treatment in headaches. Cephalalgia 2011, 31:550-561.
66. Colloca L., Benedetti F. How prior experience shapes placebo analgesia. Pain 2006, 124:126-133.
67. Rosenthal R. Experimenter effects in behavioral research 1966, Appleton Century Crofts, New York.
68. Golomb B.A., McGraw J.J., Evans M.A., Dimsdale J.E. Physician response to patient reports of adverse drug effects. Drug Saf 2007, 80:669-678.
69. Rief W., Nestoriuc Y., von Lilienfeld-Toal A., Dogan I., Schreiber F., Hofmann S.G., et al. Differences in adverse effect reporting in placebo groups in SSRI and tricyclic antidepressant trials. A systematic review and meta-analysis. Drug Saf 2009, 32:1041-1056.
70. Benedetti F., Lanotte M., Lopiano L., Colloca L. When words are painful - unraveling the mechanisms of the nocebo effect. Neuroscience 2007, 147:260-271.
71. Scott D.J., Stohler C.S., Egnatuk C.M., Wang H., Koeppe R.A., Zubieta J.K. Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses. Arch Gen Psychiatry 2008, 65:220-231.
72. Ryvlin P., Nashef L., Tomson T. Prevention of sudden unexpected death in epilepsy: a realistic goal?. Epilepsia 2013, 54(Suppl. 2):23-28.
73. Ryvlin P., Cucherat M., Rheims S. Risk of sudden unexpected death in epilepsy in patients given adjunctive antiepileptic treatment for refractory seizures: a meta-analysis of placebo-controlled randomised trials. Lancet Neurol 2011, 10:961-968.
74. Epstein R.M., Alper B.S., Quill T.E. Communicating evidence for participatory decision making. J Am Med Assoc 2004, 291:2359-2366.
75. Møller A., Jensen L.H., Skrumsager B., Blatt-Lyon B., Pedersen B., Dam M. Inhibition of photosensitive seizures in man by the beta-carboline, ZK 95962, a selective benzodiazepine receptor agonist. Epilepsy Res 1990, 5:155-159.
76. Kasteleijn-Nolst Trenité D.G., Genton P., Parain D., Masnou P., Steinhoff B.J., Jacobs T., et al. Evaluation of brivaracetam, a novel SV2A ligand, in the photosensitivity model. Neurology 2007, 69:1027-1034.
77. French J.A., Krauss G.L., Kasteleijn D., DiVentura B.D., Bagiella E. Effects of marketed antiepileptic drugs and placebo in the human photosensitivity screening protocol. Neurotherapeutics 2014, 11:412-418.
78. Tang V., Michaelis R., Kwan P. Psychobehavioral therapy for epilepsy. Epilepsy Behav 2014, 32:147-155.
79. Enck P., Benedetti F., Schedlowski M. New insights into the placebo and nocebo responses. Neuron 2008, 59:195-206.
80. Kam-Hansen S., Jakubowski M., Kelley J.M., Kirsch I., Hoaglin D.C., Kaptchuk T.J., et al. Altered placebo and drug labeling changes the outcome of episodic migraine attacks. Sci Transl Med 2014, 6:218ra5.
81. Tudur Smith C., Dwan K., Altman D.G., Clarke M., Riley R., Williamson P.R. Sharing individual participant data from clinical trials: an opinion survey regarding the establishment of a central repository. PLoS One 2014, 9(5):e97886.
82. Rief W., Bingel U., Schedlowski M., Enck P. Mechanisms involved in placebo and nocebo responses and implications for drug trials. Clin Pharmacol Ther 2011, 90:722-726.