The evidence behind placebo effects and the clinical and ethical considerations are examined in a review in this week’s edition of The Lancet. The analysis is the work of Damien G Finniss, University of Sydney Pain Management and Research Institute, Royal North Shore Hospital, Sydney, Australia, and colleagues.

The authors comment: “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.”

The fact that there is not one placebo effect but many is a fundamental conclusion in the review. Mechanistically, there are very different placebo effects. Meaning that, the psychosocial situation of a patient when they receive a treatment can be very influential in changing a person’s physiology.

Many mechanisms have been identified from the psychological viewpoint. They include:

• expectations about the effect of a treatment
• desire for symptom relief
• several learning processes such as classical conditioning and social observation

Most research into the biological mechanisms of placebo effects takes into account endogenous opioids and pain relief, from a neurobiological viewpoint. Some placebo effects are mediated by endogenous opioids and others are not. An opioid is a chemical that works by binding to opioid receptors, which are found principally in the central nervous system. Interestingly, if a patient is given treatment with an opioid drug for pain relief and this is then substituted by a placebo, the subsequent placebo effect is mediated by endogenous opioids. On the other hand, if the same process is applied with a non-opioid pain drug, the ensuing placebo effect is mediated by a completely different mechanism. More complex technology and research methodology has acknowledged different placebo effects across the body. There are placebo-induced changes in heart, lung and hormone function, and different effects in other conditions such as Parkinson’s disease.

The implications for clinical practice are examined in the review. The authors describe recent examples of how placebo effects can operate in clinical practice. Possibly, the most significant point 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 illustrate the example with the open-hidden paradigm. It is an experiment where some patients receive a drug via a computer pump and do not 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 reveal that many drugs are far less efficient when the patient does not know they are receiving them. This demonstrates 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. In some instances it may interact with a therapy, making the drug component more effective, in addition to the normal placebo component.

Additional examples of placebo effects operating in clinical situations support these findings. They demonstrate that when several 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. This indicates that 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”.

The authors comment regarding the ethics of enhancing placebo effects in clinical care: “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 comment: “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 say in conclusion: “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.”

“Biological, clinical, and ethical advances of placebo effects”
Damien G Finniss, Ted J Kaptchuk, Franklin Miller, Fabrizio Benedetti
Lancet 2010; 375: 686-95
The Lancet

Written by Stephanie Brunner (B.A.)