Placebo stimulates neuroplasticity in depression: implications for clinical practice and research

Clinical Pharmacology & Therapeutics, 2009

Placebos were historically defined as inert substances (e.g., sugar or bread pills) that cause symptom improvement but are now characterized more broadly to include contextual aspects of both active and inactive treatments that contribute to symptom improvement in therapeutic settings. These contexts may be associated with the environment, including the size and color of a pill, a doctor's demeanor, or the invasiveness and cost of a treatment. The context may also be generated by the patient's prior experience or expectations about the efficacy of a treatment. Placebo effects are cognitive, behavioral, or biological responses to

The Lancet Neurology, 2002

Recent evidence suggests that the placebo effect is mediated by the dopaminergic reward mechanisms in the human brain and that it is related to the expectation of clinical benefit. On the basis of this theory, we propose some criteria for the proper investigation of the placebo effect, and review the evidence for a placebo effect in Parkinson's disease, depression, pain, and other neurological disorders. We also discuss the evidence for the use of placebos in long-term substitution programmes for the treatment of drug addiction.

2006

Placebo is a Latin word and means 'I shall please' and refers to an inert substance. People are concerned for placebo effects in various ways. The public is impressed by the promise of self-control of health issues and the broadening limits of endogenous human capability. Scientists are interested in the fact that human experiences and expectations could influence the progress of their patient's health with sometimes unpredictable results. The biology of placebo effects refers to a complex system not fully understood. There is evidence that includes learning responses and conscious cognitive factors and related neurological processes. The neurobiology of the placebo effects has been investigated recently and the underlying mechanisms were enlightened. Placebo effects have been investigated in pain, depression, immune diseases and cancer and are applied in psychiatry and even in surgery procedures. Placebo treatment is not something new and is used in the history of mankind as an effective medication. Nowadays many alternative medications base their efficacy in the application of placebo effects. They are considered as a self-influence and control of health issues that broadens the limits of endogenous human capability. In medicine, apart from their use as alternative drugs, they are used as controls in trials which measure the effectiveness of conversional drugs.

PsycCRITIQUES, 2009

Reviews the book, "Placebo effects: Understanding the mechanisms in health and disease" by Fabrizio Benedetti (see record 2009-02085-000). Benedetti's book is a lucid and extensive review entrenched in the neuroscience of placebo research and heralding the importance of this area of study. Benedetti addresses his book to medical students, doctors, and nurses, who will surely find his compilation a useful source of timely information. He also addresses his book to social scientists, but they may find his exposition unbalanced, with only cursory allusions to relevant placebo studies from their purview. This latter crowd would be wide of the mark to take Benedetti for a rabid fan of neurobiological reductionism because his superb research and careful presentations suggest that he is keenly aware of other perspectives, including those of Anne Harrington, Daniel Moerman, and Irving Kirsch. Alas, the field is vast and the cover of Benedetti's book-depicting a structural brain scan, an electrophysiological trace, and molecule charts-may cue the intelligent reader to the author's choice of tenor. This choice was likely both strategic and pragmatic. With definitional imprecision of elementary terms continuing to present a major shortcoming, however, Benedetti must realize that many practitioners simultaneously construe placebos as a screening tool to unmask malingering, a method to control for psychogenic effects, and a compelling example of the power of the mind . While Benedetti acknowledges that we should sort out ethical and practical conceptualizations regarding placebos in order to forge clear directions for future research, placebos-including their responses and effects-will likely remain a moving target until we refine an overarching approach to this burgeoning field. (PsycINFO Database Record (c) 2009 APA, all rights reserved)

Psychopharmacology, 2004

Rationale: High placebo response rates are a confound in treatment trials for major depressive disorder (MDD). A method for prospective identification of placebo responders could enhance the efficiency of clinical trials. Objective: The objective was to identify the neurophysiological, symptomatic, and cognitive characteristics of subjects who were likely to respond to placebo in clinical trials for MDD. Methods: Fifty-one subjects with MDD were treated in clinical trials with either fluoxetine (n=24) or venlafaxine (n=27) versus placebo. All subjects underwent pretreatment assessment with quantitative electroencephalographic (QEEG) power and cordance, as well as symptom ratings and neuropsychological testing. After a 1-week single-blind placebo lead-in, subjects were randomized to double-blind placebo controlled treatment with a medication or placebo. At the end of 8 weeks, the blind was broken and treatment response assessed. Response was defined by a final Hamilton Depression Rating Scale score of ≤10. Results: Of the medication-treated and placebo-treated subjects, 52% (13/25) and 38% (10/26) responded. Placebo responders had lower pretreatment frontocentral cordance in the theta frequency band than all other subjects (P<0.006) and medication responders in particular (P<0.004). Placebo responders also had faster cognitive processing time, as assessed by neuropsychological testing, and lower reporting of late insomnia (P<0.03). Exploratory examination of a multiple variable model for predicting placebo response was conducted using logistic regression, in which these three pretreatment measures accurately identified 97.6% of eventual placebo responders. Conclusions: These findings suggest that combined clinical, neurophysiological, and cognitive assessments of prospective subjects for clinical trials may be useful for identifying MDD subjects who are likely to show robust response to placebo. Prospective validation of these results in a larger, independent sample of subjects is necessary to establish the reliability and usefulness of this method for prospective identification of placebo responders.

2006

Neuroimage, 2004

Dialogues in clinical neuroscience, 2002

With its naturally fluctuating course, depression is a highly placebo-responsive condition: mean placebo response rates in antidepressant clinical trials are 30% to 40%. We review the history and terminology of placebo and the proposed mechanisms underlying the placebo response, including the physician-patient relationship and biological, sociocultural, and treatment situation factors. We identify the predictors and patterns of placebo response in depressed patients, both within and outside of the clinical trial context, and differentiate between true drug response and placebo pattern response. We discuss the strategies now being advanced to minimize the placebo response given the increased placebo drift reported in recent trials, and the ethical guidelines governing placebo administration. Potential areas for future research include the identification of biological markers of placebo response, such as functional neuroimaging and quantitative electroencephalography, the development ...

Annals of the New York Academy of Sciences, 2009

Recent years have seen a renewed interest in understanding the placebo effect. From the beginning of controlled trials, when putatively active treatments were for the first time compared against "sham" controls, it was recognized that "the passions of the mind [had a wonderful and powerful influence] upon the state and disorder of the body" (Haygarth, 1801). These initial observations of placebo effects have now been corroborated across multitudes of studies in modern times (de Craen et al., 1999). Clinically significant placeboassociated improvements can occur in as few as 5% or as many as 65% of individuals in randomized, controlled trials (RCTs), depending on the central nervous system (CNS) disease process under consideration and the particular study sample under investigation. Certainly, placebo effects add to the variability in responses associated with the pathologies and treatments themselves. As a result, promising results in open, uncontrolled trials without placebo control are oftentimes no longer observable once the placebo effects are taken into account. Similarly, nocebo effects, the development of adverse events or worsening of a condition after the administration of a placebo are reported in a sizable proportion of individuals participating in clinical trials (Drici et al., 1995; Long et al., 1989).