Public Release: 

The placebo effect: Clinical and ethical considerations

Lancet

A Review in this week's edition of The Lancet looks at the evidence behind placebo effects and the clinical and ethical considerations of this research. The Review is written by Damien G Finniss, University of Sydney Pain Management and Research Institute, Royal North Shore Hospital, Sydney, Australia, and colleagues.

The authors say: "For many years, placebos have been defined by their inert content and their use as controls in clinical trials and treatments in clinical practice. Recent research shows that placebo effects are genuine psychobiological events attributable to the overall therapeutic context, and that these effects can be robust in both laboratory and clinical settings. There is also evidence that placebo effects can exist in clinical practice, even if no placebo is given."

One of the key conclusions from the Review is that there is not one placebo effect, there are many. Mechanistically, there are very different placebo effects. In other words, the psychosocial context surrounding a patient when they receive a treatment can be very powerful in changing a person's physiology.

From the psychological viewpoint, many mechanisms have been identified and include expectations about the effect of a treatment, desire for symptom relief and several learning processes such as classical conditioning and social observation.

From a neurobiological viewpoint, most research into the biological mechanisms of placebo effects is concerned with endogenous opioids and pain relief. There are some placebo effects which are mediated by endogenous opioids and others that are not. Interestingly, if a patient is given treatment with a opioid drug for pain relief and this is then substituted by a placebo, the ensuing placebo effect is mediated by endogenous opioids. However, if the same process is applied with a non-opioid pain drug, the ensuing placebo effect is mediated by an entirely different mechanism. More advanced technology and research methodology has identified different placebo effects across the body, such as placebo-induced changes in heart, lung and hormone function, and different effects in other conditions such as Parkinson's disease.

Much of the Review focuses on the implications for clinical practice, with the authors describing recent examples of how placebo effects can operate in clinical practice. Perhaps the most important message of the paper is that "you don't need to give a placebo to create a placebo effect. Placebo effects are a part of routine medical practice and are potentially active every time a patient enters a therapeutic context." The authors use the example of the open-hidden paradigm, which is an experiment where some patients receive a drug via a computer pump and don't know they are receiving it and have no interaction with a doctor. Other patients receive the same dose of the drug but by the doctor. Results show that many drugs are far less effective when you don't know you are receiving them, demonstrating that the overall outcome of a therapy is the specific therapy itself and the many factors which make the psychosocial or therapeutic context, which is the placebo component of normal therapy. This paradigm has also demonstrated that placebo effects can not only add to a routine therapy, but in some instances may interact with a therapy making the drug component more effective, in addition to the normal placebo component.

Further examples of placebo effects operating in clinical situations reinforce these findings, demonstrating that when many of the factors involved in the therapeutic context are reduced, such as the interaction between the patient and the doctor, the placebo component of therapy is diminished. In other words, there seems to be a dose-response to placebo effects. "This research is very encouraging as it now gives us some more direction to further study how placebo effects operate in clinical practice, with a view to enhancing them on a routine basis".

Regarding the ethics of enhancing placebo effects in clinical care, the authors say: "more studies of placebo effects in specific clinical settings are needed before use of treatments with the primary aim of promoting placebo responses can be recommended as evidence-based practice... Whether it is ethical to recommend a treatment primarily to produce a placebo effect is a more complicated and controversial question. "Importantly, this review highlights that you don't need to give a placebo to elicit a placebo effect, and therefore, maximising the factors that drive the placebo component of routine therapy represents an ethically sound and promising alternative to giving placebos with the sole intention of eliciting placebo effects".

They add: "To recommend or give a placebo intervention deceptively as a treatment with specific efficacy for a patient's condition violates informed consent and threatens the trust that is central to clinical practice. The available evidence suggests that the practice of disclosure to patients regarding such placebo treatments is deceptive or at least not sufficiently transparent."

They conclude: "Laboratory evidence supports the existence of several placebo mechanisms and placebo effects in both healthy volunteers and patients with a variety of medical conditions. Furthermore, clinically relevant evidence shows that placebo effects can have meaningful therapeutic effects, because of their long magnitude and duration, in different patient populations. Although substantial progress has been made in understanding placebo effects, much laboratory and translational clinical trial research remains to be done, with the ultimate aim of harnessing placebo effects to improve patient care."

###

Damien G Finniss, University of Sydney Pain Management and Research Institute, Royal North Shore Hospital, Sydney, Australia. T) +61 412 742 710 E) dfinniss@med.usyd.edu.au

For full Review, see: http://press.thelancet.com/placebo.pdf

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.