One of the most difficult aspects of treating pain is maintaining analgesia without overprescribing addictive pain medications such as opioids. Enter the placebo – an approach which has typically been characterized as a way of “tricking” the mind into believing that the pain has been treated, even when it hasn’t. As a result, the patient perceives less pain, and the inactive ingredients in the placebos act as a safeguard against addiction. From a treatment perspective, it’s a win-win situation. Unsurprisingly, placebos have been a well-studied treatment option within the field of anesthesiology and analgesia, both in randomized controlled trials and experimental pain settings [1,2]. One meta-analysis of randomized controlled trials of pain treatments for osteoarthritis concluded that about 75 percent of overall treatment effects were due to placebo [3].
Despite their benefits within analgesia, placebos occupy a “gray area” within medicine. On the one hand, it is clear that they work and lead to tangible treatment outcomes in many situations. On the other hand, administering a placebo involves misleading the patient about their own treatment – an approach which makes many physicians uncomfortable, and is impractical in the long-term. Should the placebo fail, it could lead to a breach in trust between patient and physician, and even worse: a discontinuation of care.
These considerations led a team of researchers at Harvard Medical School to ask what seemed like a contradictory question: could a placebo work without the deception? Instead of harnessing the power of expectation, the authors decided to try another approach: classical conditioning [4].
Classical conditioning in anesthesia involves administering open-label placebos (conditioned stimulus) along with a more typical analgesia (unconditioned stimulus) to induce pain relief. Their hypothesis was that patients who began to associate the analgesic effects of the unconditioned stimulus with that of the open-label placebo would experience enduring pain relief even when the actual analgesic was removed. In other words, even though the patients would know that they were only taking placebos, the analgesic effect would persist.
In order to test their hypothesis, the authors randomized a cohort of 51 patients between the ages of 18 and 75. Baseline pain before spine surgery was assessed. In addition, the patients were educated about (1) the definition of a placebo, (2) the definition of an “open-label” placebo, (3) the ability of placebos to reduce pain in randomized control trials, and (4) the concept of classical conditioning.
Once educated, the patients were organized into two groups: one who received a conditioned open-label placebo (COLP), and one who received treatment as usual (TAU). The patients received the same amount of time with their respective physicians. Both before and after discharge, patients were prompted daily to conduct a Brief Pain Inventory and to document all drugs taken. To validate these reports, their findings were cross-referenced with medication administration records. The study was conducted for 17 days post-operation.
Despite being comparable in opioid consumption and pain score prior to the study, the authors noted key differences in analgesic outcomes between the two groups. The authors reported that COLP was associated with a 30 percent reduction in daily opioid consumption and lower worst pain scores. Notably, patients in the COLP group also appeared to discontinue opioids earlier than patients in the TAU group, a finding which could have considerable implications for the opioid epidemic.
These findings suggest that deception is not necessarily an integral part of the placebo effect, and that physicians may be able to use placebos as part of an ethical and fully-disclosed treatment plan. Even more promising is the fact that up to 84 percent of patients surveyed reported that they would be willing to take an open-label placebo as part of their treatment plan [5]. It can be anticipated that open-label placebos will be continually studied and implemented within postoperative anesthetic care with analgesia.
References
1. Geuter, S., Koban, L., & Wager, T. D. (2017). The Cognitive Neuroscience of Placebo Effects: Concepts, Predictions, and Physiology. Annual review of neuroscience, 40, 167–188. https://doi.org/10.1146/annurev-neuro-072116-031132
2. Schneider, T., Luethi, J., Mauermann, E., Bandschapp, O., & Ruppen, W. (2020). Pain Response to Open Label Placebo in Induced Acute Pain in Healthy Adult Males. Anesthesiology, 132(3), 571–580. https://doi.org/10.1097/ALN.0000000000003076
3. Zou, K., Wong, J., Abdullah, N., Chen, X., Smith, T., Doherty, M., & Zhang, W. (2016). Examination of overall treatment effect and the proportion attributable to contextual effect in osteoarthritis: meta-analysis of randomised controlled trials. Annals of the rheumatic diseases, 75(11), 1964–1970. https://doi.org/10.1136/annrheumdis-2015-208387
4. Flowers, K. M., Patton, M. E., Hruschak, V. J., Fields, K. G., Schwartz, E., Zeballos, J., Kang, J. D., Edwards, R. R., Kaptchuk, T. J., & Shreiber, K. L. (2021). Conditioned open-label placebo for opioid reduction after spine surgery: a randomized controlled trial. Pain, 162(6), 1828-1839. https://doi.org/10.1097/j.pain.0000000000002185
5. Hull, S. C., Colloca, L., Avins, A., Gordon, N. P., Somkin, C. P., Kaptchuk, T. J., & Miller, F. G. (2013). Patients’ attitudes about the use of placebo treatments: telephone survey. BMJ (Clinical research ed.), 347, f3757. https://doi.org/10.1136/bmj.f3757