The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil.

Bingel UWanigasekera VWiech KNi Mhuircheartaigh RLee MCPloner MTracey I. Sci Transl Med. 2011 Feb 16;3(70):70ra14.

A little over a month ago we posted an article that suggested there was a clinical benefit to placebos when patients are instructed 1) that they are taking placebos and 2) that the placebos are beneficial.  The study highlighted the importance of explaining the benefits of treatments to patients, even if it is a placebo. Bingel et al. took this a step further by evaluating how different expectations (both positive and negative) may alter the effect of a prescription analgesic in healthy volunteers. The study recruited 22 healthy volunteers to undergo four trials (each with 10 standardized painful heat stimuli): 1) no analgesic (saline infused intravenously), 2) opioid analgesic infused without being told that the medication was being delivered (no expectancy), 3) continued opioid analgesic and being told that they were receiving the analgesic (positive expectancy), and 4) continued opioid analgesic but were told told that the analgesic was stopped to see how their pain increased (negative expectancy). Subjective and functional brain MRI data (to record brain activity) were gathered during the study. In advance of data collection, the authors performed their full study protocol with only saline and found that there was no evidence of habituation or sensitization (after four trials people responded to the pain stimulus similar to the first trial). The study found that when patients expected a positive outcome their pain was reduced almost in half but when the patient had negative expectations (they thought the medicine was stopped and the pain would be greater) their pain was as if they were not taking an analgesic. They supported their evidence by demonstrating that brain activity was different between positive and negative expectation conditions. 

The authors suggest that their data indicates that clinicians should consider patients’ beliefs and expectations during treatment regimes to improve treatment outcomes. In many ways this study agrees with the article we previously posted. It demonstrates the importance of educating our patients about the potential benefits of their treatments. Furthermore, this study highlights the opposite side of the placebo effect (nocebo). If a patient does not think that a particular intervention is going to work then, based on this data, it might not work.  Sometimes we need to be sensitive to different cultural views towards certain treatments (for optimizing placebo/nocebo responses). In a time when we are being pushed to see more patients in a limited time this data provides additional evidence that we need to slow down and spend more time educating our patients about why their treatments will be beneficial. The treatment of physical injuries requires a partnership between the clinician and patient, in which both agree to the optimal treatment regimen to improve patient symptoms.

Written by: Jeffrey Driban
Reviewed by: Joseph Zeni