Categories

Placebo effect works even if patients know they’re getting a sham drug

Patients can benefit from being treated with sham drugs even if they are told they contain no active ingredient, scientists have found. The finding suggests that the placebo effect could work without the need for any deception on the part of the doctor, as had been previously thought.

Placebo effect works even if patients know they’re getting a sham drug

Alok Jha, Science Correspondent
guardian.co.uk, Wednesday 22 December 2010 21.59 GMT 

http://www.guardian.co.uk/science/2010/dec/22/placebo-effect-patients-sham-drug

Patients can benefit from being treated with sham drugs even if they are told they contain no active ingredient, scientists have found. The finding suggests that the placebo effect could work without the need for any deception on the part of the doctor, as had been previously thought.

When a patient undergoes a sham treatment for a disorder – such as taking a sugar pill – but still experiences a measurable improvement in their condition this is known as the placebo effect. It was widely thought, however, that the effect only works if the patient believes that the treatment they are receiving contains an active ingredient. Dummy treatments that might elicit the placebo effect are often used in clinical trials as a comparison group to allow scientists to measure the additional effects of experimental medicines.

To investigate the limits of placebo, Prof Ted Kaptchuk of Harvard Medical School’s Osher Research Center divided 80 patients suffering from irritable bowel syndrome (IBS) into two groups: one received no treatment and the other was given dummy pills to take twice a day. The second group was told by the doctors that they would be taking “placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS-symptoms through mind-body self-healing processes”.

“Not only did we make it absolutely clear that these pills had no active ingredient and were made from inert substances, but we actually had ‘placebo’ printed on the bottle,” said Kaptchuk. “We told the patients that they didn’t have to even believe in the placebo effect. Just take the pills.”

The results, published in the scientific journal PLoS ONE, showed that the placebo pills were more effective at relieving symptoms compared with doing nothing at all.

“I didn’t think it would work,” says senior author Anthony Lembo of the Beth Israel Deaconess Medical Center and an expert on IBS. “I felt awkward asking patients to literally take a placebo. But to my surprise, it seemed to work for many of them.”

In the trial, the IBS patients were monitored for three weeks. The group on placebo pills showed improvements both at the half way point and at the end of the period, when compared with the no-treatment group. By the end of the trial, almost twice as many patients treated with placebo showed adequate relief of symptoms compared with the control group. Patients taking the placebo also doubled their average rate of improvement to that achieved with the most powerful IBS medications.

“Directly harnessing placebo effects in a clinical setting has been problematic because of a widespread belief that beneficial responses to placebo treatment require concealment or deception,” wrote the researchers in PLoS ONE. “This belief creates an ethical conundrum: to be beneficial in clinical practice placebos require deception but this violates the ethical principles of respect for patient autonomy and informed consent.”

Nevertheless, a recent survey of doctors in the US, published in the British Medical Journal, found that while only small numbers of American physicians use inert placebo pills and injections, around half prescribed treatments that they considered to have no specific effect on patients’ conditions and are used solely as placebos. “Given this situation, finding effective means of harnessing placebo responses in clinical practice without deception is a high priority,” wrote the researchers.

Kaptchuk and his colleagues warned that there were limitations with their study, given its small size and limited time span. They called their result a “proof-of-concept” pilot study that would need to be repeated with larger numbers of people and over longer periods, to investigate the long-term effects of the placebo.

“Nevertheless,” said Kaptchuk, “these findings suggest that rather than mere positive thinking, there may be significant benefit to the very performance of medical ritual. I’m excited about studying this further. Placebo may work even if patients know it is a placebo.”

The study being reported on:

Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome

Ted J. Kaptchuk1,2*, Elizabeth Friedlander1, John M. Kelley3,4, M.

Norma Sanchez1, Efi Kokkotou1, Joyce P. Singer2, Magda Kowalczykowski1, Franklin G. Miller5, Irving Kirsch6, Anthony J. Lembo1 

1 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Osher Research Center, Harvard Medical School, Boston, Massachusetts, United States of America,

3 Psychology Department, Endicott College, Beverly, Massachusetts, United States of America, 4 Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 5 Department of Bioethics, National Institutes of Health, Bethesda, Maryland, United States of America, 6 Department of Psychology, University of Hull, Hull, United Kingdom 

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0015591

Abstract
Background

Placebo treatment can significantly influence subjective symptoms.

However, it is widely believed that response to placebo requires concealment or deception. We tested whether open-label placebo (non-deceptive and non-concealed administration) is superior to a no-treatment control with matched patient-provider interactions in the treatment of irritable bowel syndrome (IBS). 

Methods
Two-group, randomized, controlled three week trial (August 2009-April

2010) conducted at a single academic center, involving 80 primarily female (70%) patients, mean age 47±18 with IBS diagnosed by Rome III criteria and with a score ≥150 on the IBS Symptom Severity Scale (IBS-SSS). Patients were randomized to either open-label placebo pills presented as “placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes”

or no-treatment controls with the same quality of interaction with providers. The primary outcome was IBS Global Improvement Scale (IBS-GIS). Secondary measures were IBS Symptom Severity Scale (IBS-SSS), IBS Adequate Relief (IBS-AR) and IBS Quality of Life (IBS-QoL).

Findings
Open-label placebo produced significantly higher mean (±SD) global improvement scores (IBS-GIS) at both 11-day midpoint (5.2±1.0 vs.

4.0±1.1, p<.001) and at 21-day endpoint (5.0±1.5 vs. 3.9±1.3, p = .002). Significant results were also observed at both time points for reduced symptom severity (IBS-SSS, p = .008 and p = .03) and adequate relief (IBS-AR, p = .02 and p = .03); and a trend favoring open-label placebo was observed for quality of life (IBS-QoL) at the 21-day endpoint (p = .08).

Conclusion
Placebos administered without deception may be an effective treatment for IBS. Further research is warranted in IBS, and perhaps other conditions, to elucidate whether physicians can benefit patients using placebos consistent with informed consent.

Trial Registration ClinicalTrials.gov NCT01010191

Citation: Kaptchuk TJ, Friedlander E, Kelley JM, Sanchez MN, Kokkotou E, et al. (2010) Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome. PLoS ONE 5(12): e15591. doi:10.1371/journal.pone.0015591

Another interesting related article:

Homeopathy and the nocebo effect.
Ben Goldacre

The Guardian, Saturday 28 November 2009

Dr Peter Fisher from the Royal London Homeopathic Hospital (funded by the NHS) says homeopathic pills have physical side-effects. Can a sugar pill have a side-effect?

This week the parliamentary science and technology committee looked into the the funding of homeopathy on the NHS and the evidence behind the decision of the MHRA, which regulates medicines, to allow homeopathy sugar pill labels to make medical claims without evidence of efficacy. 

There were comedy highlights, as you might expect from any serious inquiry into an industry where sugar pills have healing powers conferred upon them by being shaken with one drop of the ingredient which has been diluted so extremely that it equates to one molecule of the substance in a sphere of water whose diameter is roughly the distance from the Earth to the sun. 

The man from Boots said he had no evidence that homeopathy pills worked, but he sold them because people wanted to buy them. The man from the pill manufacturers’ association said negative trials about homeopathy were often small, with an average of 65 people, and “all statisticians” agreed you need 500 people for a proper trial. Not only is it untrue that you necessarily need this many people ; he then cited, in his favour, a positive homeopathy trial with just 25 patients in it (http://content.karger.com/produktedb/produkte.asp?typ=fulltext&amp;file=000209386). 

The best moment was Dr Peter Fisher from the (NHS-funded) Royal London Homeopathic hospital explaining that homeopathic sugar pills have physical side-effects – so they must be powerful. 

Can a sugar pill have a side-effect? Interestingly, a paper published in the journal Pain next month (http://www.painjournalonline.com/article/S0304-3959%2809%2900399-6/abstract) looks at just this issue. It found every single placebo-controlled trial ever conducted on a migraine drug, and looked at the side-effects reported by the people in the control group, who received a dummy “placebo” sugar pill instead of the real drug. Not only were these side-effects common, they were also similar to those of whatever drug the patients thought they might be receiving. 

This is nothing new. A study in 2006 (http://www.psychosomaticmedicine.org/cgi/content/abstract/68/3/478%E2%80%9D%3E) sat 75 people in front of a rotating drum to make them feel nauseous, and gave them a placebo sugar pill: 25 were told it was a drug that would make the nausea worse. It did get worse, and they also exhibited more gastric tachyarrhythmia, the abnormal stomach activity that frequently accompanies nausea. 

A paper in 2004 (http://www.ncbi.nlm.nih.gov/pubmed/15301298) took 600 patients from three different specialist drug allergy clinics and gave them either the drug that was causing their adverse reactions, or a dummy pill with no ingredients: 27% of the patients experienced side-effects such as itching, malaise and headache from the placebo dummy pill. 

And a classic paper from 1987

(http://www.ncbi.nlm.nih.gov/pubmed/3621780?dopt=Abstract) looked at the impact of listing side-effects on the treatment consent form. This was a large trial comparing aspirin against placebo, conducted in three different centres. In two, the form outlined various gastrointestinal side-effects, and in these centres there was a sixfold rise in the number of people reporting such symptoms and dropping out of the trial.

This is the amazing world of the nocebo effect, where negative expectations can induce unpleasant symptoms, in the absence of a physical cause. 

And in any case, it doesn’t help homeopaths: In 2003 Professor Edzard Ernst conducted a systematic review (http://dx.doi.org/10.1016/S1475-4916(03)00007-9), finding every homeopathy trial that reported side-effects. There was no significant difference in the rates of side-effects between patients given placebo and those given homeopathic remedies. 

The world of the homeopath is reductionist, one-dimensional, and built on the power of the pill: it cannot accommodate the fascinating reality of connections between mind and body which have been elucidated by science. 

The next time you find yourself trapped at dinner next to some bore who’s decided in middle age that they have secret mystical healing powers, while they earnestly explain how their crass efforts at selling sugar pills represent a meaningful political stand against the crimes of big pharma, just think: some lucky person, somewhere in the world, is sat next to a nocebo researcher.

Leave a Reply

  

  

  

You can use these HTML tags

<a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>