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VIEWS AND REVIEWS: Nico J. Diederich and Christopher G. Goetz The placebo treatments in neurosciences: New insights from clinical and neuroimaging studies Neurology 2008; 71: 677-684 [Abstract] [Full text] [PDF]

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The placebo treatments in neurosciences: New insights from clinical and neuroimaging studies

Barry S. Oken   (21 November 2008)

Reply from the Authors

Nico J. Diederich, Christopher G Goetz, Rush University Medical Center, Chicago   (21 November 2008)

The placebo treatments in neurosciences: New insights from clinical and neuroimaging studies 21 November 2008
Barry S. Oken, Oregon Health & Science University 3181 SW Sam Jackson Park Rd., Portland, OR 97239 Send Correspondence to journal: Re: The placebo treatments in neurosciences: New insights from clinical and neuroimaging studies oken{at}ohsu.edu Barry S. Oken	Drs. Diederich and Goetz provide further awareness of issues related to placebo. [1] However, some of the authors’ statements and conclusions are debatable. The article focused on clinical changes in the placebo arm of clinical trials yet most researchers would not use the term ‘placebo’ for some changes occurring in this arm. The Hawthorne effect—a change in outcome measures solely related to being in a clinical study—might arise from signing a consent form and having the outcome assessments measured. [2] Simply studying the placebo arm of a clinical trial is not optimal, and understanding placebo effects requires better control groups. Having a no-treatment arm in clinical trials considers the Hawthorne and natural history effects and the authors note the limitations. The cited studies of placebo in depression with no satisfactory control group are problematic because, in addition to natural history and Hawthorne effects, the “placebo” arms often have some intervention. Experimental designs are more effective in advancing our understanding of placebo effects. While hidden versus open administration of medications and pharmacologic alterations of the placebo effect may help with short-term placebo effects, longer term placebo effects are particularly relevant. A cross-over design with no-drug versus placebo and using data only prior to the cross-over may help. [3] Ethical issues might arise in investigating placebo effects since some element of deception may enhance the scientific value of such studies. Deception is critical for certain topics of experimental psychology research, such as racism, and guidelines for deception in research are available. While deception in clinical trials should be minimized, some deception is likely helpful when studying placebo effects or when trying to avoid major contamination of the direct biologic effects of the intervention with expectancy effects. The authors also refer to top-down expectancy effects. Although it is useful to differentiate more cortically mediated effects for which subjects are aware versus those who are not aware, there are conditioned aspects to what are considered placebo effects, including those occurring in rodents and humans. [4,5] While the cortex might be included as part of the network of activation, using the term “top-down” seems misleading. Some of the imaging studies cited by the authors show frontal activation in humans, but these changes are sometimes secondary to mu-opioid receptor activation. This is clearly an important area despite these concerns. Reviews with other perspectives are also available. [5] References 1. Diederich NJ. Goetz CG. The placebo treatments in neurosciences. Neurology 2008;71:677-684. 2. Bouchet C, Guillemin F, Briancon S. Nonspecific effects in longitudinal studies: impact on quality of life measures. Journal of Clinical Epidemiology 1996;49:15-20. 3. Oken BS, Flegal K, Zajdel D, Kishiyama S, Haas M, Peters D. Expectancy effect: impact of pill administration on cognitive performance in healthy seniors. Journal of Clinical and Experimental Neuropsychology 2008;30:7-17. 4. Ader R, Cohen N. Behaviorally conditioned immunosuppression and murine systemic lupus erythematosus. Science 1982;215:1534–1536. 5. Oken BS. Placebo effects: Clinical aspects and neurobiology, Brain 2008;131:2812-2823. Disclosure: The author reports no disclosures.
Reply from the Authors 21 November 2008
Nico J. Diederich, Department of Neurosciences Centre Hospitalier de Luxembourg, 4, rue Barblé L-1210-Luxembourg-City Luxembourg, Christopher G Goetz, Rush University Medical Center, Chicago Send Correspondence to journal: Re: Reply from the Authors diederdn{at}pt.lu Nico J. Diederich, et al.	Our article presents available data [1] and is primarily offered to researchers and clinicians as a starting point for continued research in placebo issues in neurological disorders. New study designs are important in the examination of placebo treatment as the experimental arm of studies rather than the control group. Conducting such efforts with deception in the context of fair disclosure to study subjects is culturally sensitive in many societies even if the scientific issues are considered pivotal. We offer the "top-down" paradigm as a model for consideration, but accept the distinction between a primarily cortical generation of effects and cortical involvement that reflects secondary activation patterns. Disclosure: The authors report no disclosures.