A study published this month in Science Translational Medicine by Rami Burstein’s group from Harvard Medical School, describes some aspects of the so-called placebo effect. The placebo effect is seen when an inert substance or treatment with no biological activity turns out to have some therapeutic effect and benefits patients.
In clinical trials, a placebo is usually given as a control when evaluating the efficacy of a drug: for example if a drug is administered as a pill, a placebo could consist of a similar pill composed of the same inactive ingredients but lacking the drug.
The placebo effect has been known for a long time, but how it works – that is by what mechanisms it may exert a therapeutic effect – is still poorly known. Burstein and colleagues now examined the placebo effect in the context of a painkilling treatment for migraine. The scientists tested whether the information provided to patients about a migraine therapy could influence the treatment’s efficacy.
They selected 66 patients who experienced regular episodic migraine (about 4 attacks/month). At the onset of 6 subsequent attacks, each patient randomly received either a painkiller (Maxalt) or a placebo; each pill was labeled once as “Maxalt” (positive information), once as “Maxalt or placebo”, and once as “placebo”. In this way, the researchers could evaluate whether the patients’ response to the real drug or to the placebo depended on the information they received about it.
The scientists found that, whereas untreated patients experienced an increase in pain (of about 15%), patients who were given either Maxalt or placebo reported different degrees of pain relief that depended not only on the type of pill they received, but also on what they thought they were receiving. In particular it was observed that:
- properly labeled Maxalt was the most effective pain-relief treatment (about 47% decrease in pain);
- properly labeled placebo had a painkilling effect (about 14% decrease in pain); this observation indicates that the ritual of taking a pill contributes to the treatment’s effect, because in this case the patients were aware that the pill did not contain any drug;
- the efficacy of either Maxalt or placebo increased when positive information was provided: in other words, Maxalt and placebo were more effective when either pill was labeled as Maxalt so that patients were convinced that they were taking the drug;
- surprisingly, placebo labeled as Maxalt, and Maxalt labeled as placebo had similar efficacies.
These last two observations indicate that patients’ expectancy affects the activity of the pain-relief treatment. What else can be inferred from these findings?
This work confirms previous results, suggesting that a placebo acts through psychobiological mechanisms that imply expectancy – patients expect that the drug will work – and a relief from anxiety derived from the ritual of taking medication. Thus, expectations of health improvement, motivation, feeling of reward and anxiety reduction all work together to increase the success of a therapeutic treatment.
The biological mechanisms that are set off by this placebo-induced psychological state and that will promote self-healing are still speculative and certainly need thorough investigation. There are also additional implications. We should try to answer questions like ‘in what therapeutic contexts is the placebo effect significant?’ and ‘which diseases can be better treated by taking advantage of the placebo effect?’
Furthermore, if a placebo labeled as a drug has some therapeutic properties, it means that it could be given in combination with a real medication to boost the drug’s effects. In this combination it would be possible to reduce the drug’s doses necessary to reach the therapeutic response, and consequently reduce its side effects.
But how to take advantage of the placebo effect while treating patients, without providing false information? Ethically it is not acceptable to administer a placebo to a patient telling him that he’s been given a drug. On the other hand, as Burstein’s work shows, the placebo is less effective if the patient knows its true identity.
To solve this intricacy and implement the benefits of the placebo in the clinics much more work is needed. This will involve psychologists, but also biologists and neuroscientists. The first ones will have to help stimulate in patients the psyche-dependent, healing-inducing mechanisms associated with a placebo, the latter will have to decipher the biochemical mechanisms through which our brain transmits to the body those psychological states and emotions that promote self-healing.
Photo: Flickr, klestaaaaaa
Kam-Hansen S, Jakubowski M, Kelley JM, Kirsch I, Hoaglin DC, Kaptchuk TJ, & Burstein R (2014). Altered placebo and drug labeling changes the outcome of episodic migraine attacks. Science translational medicine, 6 (218) PMID: 24401940
Finniss DG, Kaptchuk TJ, Miller F, & Benedetti F (2010). Biological, clinical, and ethical advances of placebo effects. Lancet, 375 (9715), 686-95 PMID: 20171404
migraine, placebo, label, painkiller, psychology