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  • The International Journal of Neuropsychopharmacology, Volume 15, Issue 7
  • August 2012, pp. 1003-1014

Placebo-related effects in clinical trials in schizophrenia: what is driving this phenomenon and what can be done to minimize it?

  • Larry Alphs (a1), Fabrizio Benedetti (a2), W. Wolfgang Fleischhacker (a3) and John M. Kane (a4)
  • DOI: http://dx.doi.org/10.1017/S1461145711001738
  • Published online: 05 January 2012
Abstract
Abstract

The effect of placebo observed in schizophrenia clinical trials represents a growing problem that interferes with signal detection for treatments, increases costs of development, discourages investment in schizophrenia research and delays the introduction of new treatments. This paper seeks to clarify key issues related to this problem and identify potential solutions to them. Differences between placebo effect and response are characterized. Recent insights into the central nervous system mechanisms of placebo effect are described. This is followed by a description of protocol/study design and study conduct issues that are contributing to a growing placebo effect in clinical trials. Potential solutions to these problems are provided.

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Copyright
The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence <http://creativecommons.org/licenses/by-nc-sa/2.5/>. The written permission of Cambridge University Press must be obtained for commercial re-use.
Corresponding author
Address for correspondence: L. Alphs, M.D., Ph.D., Therapeutic Area Leader in Psychiatry, Janssen Scientific Affairs, LLC, 1125 Trenton Harbourton Road, A32501, Titusville, NJ, USA. Tel.: 609-730-3693Fax: 609-647-0801Email: lalphs@its.jnj.com
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F Benedetti (2008 a). Mechanisms of placebo and placebo-related effects across diseases and treatments. Annual Reviews Pharmacology and Toxicology 48, 3360.

F Benedetti (2008 b). Placebo Effects: Understanding the Mechanisms in Health and Disease. Oxford, UK: Oxford University Press.

F Benedetti , L Colloca , E Torre , M Lanotte , (2004). Placebo-responsive Parkinson patients show decreased activity in single neurons of subthalamic nucleus. Nature Neuroscience 7, 587588.

F Benedetti , M Lanotte , L Colloca , A Ducati , (2009). Electrophysiological properties of thalamic, subthalamic and nigral neurons during the anti-Parkinsonian placebo response. Journal of Physiology 587, 38693883.

F Benedetti , M Lanotte , L Lopiano , L Colloca (2007). When words are painful: unraveling the mechanisms of the nocebo effect. Neuroscience 147, 260271.

Y-F Chen , S-J Wang , NA Khin , MJ Hung , (2010). Trial design issues and treatment effect modeling in multi-regional schizophrenia trials. Pharmaceutical Statistics 9, 217229.

CU Correll , AK Malhotra , K Saurabh , M McMeniman , (2003). Early prediction of antipsychotic response in schizophrenia. American Journal of Psychiatry 160, 20632065.

M Davidson , S Galderisi , M Weiser , N Werbeloff , (2009). Cognitive effects of antipsychotic drugs in first-episode schizophrenia and schizophrenia disorder: a randomized, open-label clinical trial (EUFEST). American Journal of Psychiatry 166, 675682.

R de la Fuente-Fernández , TJ Ruth , V Sossi , M Schulzer , (2001). Expectation and dopamine release: mechanism of the placebo effect in Parkinson's disease. Science 293, 11641166.

F Eippert , U Bingel , ED Schoell , J Yacubian , (2009). Activation of the opioidergic descending pain control system underlies placebo analgesia. Neuron 63, 533543.

P Enck , F Benedetti , M Schedlowski (2008). New insights into the placebo and nocebo responses. Neuron 59, 195206.

WW Fleischhacker , T Burns and The European Group for Research in Schizophrenia (2002). Feasibility of placebo-controlled clinical trials of antipsychotic compounds in Europe. Psychopharmacology 162, 8284.

WW Fleischhacker , P Czobor , M Hummer , G Kemmler , (2003). Placebo or active control trials of antipsychotic drugs? Archives of General Psychiatry 60, 458464.

GE Goldberg , RS Goldman , KE Burdick , AK Malhotra , (2007). Cognitive improvement after treatment with second-generation antipsychotic medications in first-episode schizophrenia: is it a practice effect? Archives of General Psychiatry 64, 11151122.

M Hummer , R Holzmeister , G Kemmler , U Eder , (2003). Attitudes of patients with schizophrenia toward placebo-controlled clinical trials. Journal of Clinical Psychiatry 64, 277281.

JM Kane , CU Correll , DC Goff , B Kirkpatrick , (2009). A multicenter, randomized, double-blind, placebo-controlled, 16-week study of adjunctive aripiprazole for schizophrenia or schizoaffective disorder inadequately treated with quetiapine or risperidone monotherapy. Journal of Clinical Psychiatry 70, 13481357.

G Kemmler , M Hummer , C Widschwendter , WW Fleischhacker (2005). Dropout rates in placebo-controlled and active-control clinical trials of antipsychotic drugs. A meta-analysis. Archives of General Psychiatry 62, 13051312.

AS Kemp , NR Schooler , AH Kalali , L Alphs , (2008). What is causing the reduced drug-placebo difference in recent schizophrenia clinical trials and what can be done about it? Schizophrenia Bulletin 36, 504509.

BJ Kinon , L Chen , H Ascher-Svanum , VL Stauffer , (2008). Predicting response to atypical antipsychotics based on early response in the treatment of schizophrenia. Schizophrenia Research 102, 230240.

BJ Kinon , L Chen , H Ascher-Svanum , V Stauffer , (2010). Early response to antipsychotic drug therapy as a clinical marker of schizophrenia response in the treatment of schizophrenia. Neuropsychopharmacology 35, 581590.

KA Kobak , B Brown , I Sharp , H Levy-Mack , (2009). Sources of unreliability in depression ratings. Journal of Clinical Psychopharmacology 29, 8285.

P Petrovic , E Kalso , KM Petersson , M Ingvar (2002). Placebo and opioid analgesia – imaging a shared neuronal network. Science 295, 17371740.

DD Price , DG Finniss , F Benedetti (2008). A comprehensive review of the placebo effects: recent advances and current thought. Annual Reviews of Psychology 59, 565590.

LW Roberts (1998). The ethical basis of psychiatric research: conceptual issues and empirical findings. Comprehensive Psychiatry 39, 99–110.

SW Woods , RV Gueorguieva , CB Baker , RW Makuch (2005). Control group bias in randomized atypical antipsychotic medication trials for schizophrenia. Archives of General Psychiatry 62, 961970.

JK Zubieta , CS Stohler (2009). Neurobiological mechanisms of placebo responses. Annals of New York Academy of Science 1156, 198210.

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The International Journal of Neuropsychopharmacology
  • ISSN: 1461-1457
  • EISSN: 1469-5111
  • URL: /core/journals/the-international-journal-of-neuropsychopharmacology
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