The opioid epidemic: could enhancing placebo effects be part of the solution?

Editor—Opioids are invaluable analgesics for postoperative pain because they are simple to administer and very effective at relieving suffering. The ethical argument made for the availability of opioids, largely as that of a basic human right, has been hampered by overprescribing and misuse leading to the current opioid epidemic.¹ Recent placebo research suggests that appropriate communication with the patient could help minimise the opioid epidemic.

Clinicians responding to the opioid epidemic have renewed interest in the way many patients suffering from acute and chronic pain can have their opioid dose reduced, or even stopped altogether, by applying greater attention to the full complement of pain management strategies, including that of psychosocial approaches.² The placebo effect is gaining greater understanding by pain management clinicians as it exemplifies the remarkable ease with which one can effectively integrate psychosocial pain management into daily practice.

Historically placebo has been disparaged as either fake medicine or merely what happens to a patient if you leave them alone. For better comprehension of this field, it can be helpful to differentiate between placebo response and placebo effect. Placebo response is attributable to regression to the mean, spontaneous remission or symptom fluctuation and can be viewed as the latter, that is, what happens if nature is left to take its course. Placebo effect is a beneficial neurobiological change that can occur simply because of expectations of the patient, caregiver, or clinician leading to the release of endogenous opioids.³

The placebo effect has been convincingly demonstrated in a number of research settings whereby subjects administered a pharmacologically active analgesic agent delivered by the caregiver using specific word framing to emphasise the analgesic potency of the agent will report greater analgesia compared to when the same agent is administered in a manner devoid of such positive wording.³ Recent neuroimaging studies provide further support for the placebo effect.⁴ It is our opinion, based on clinical and research experience, that placebo enhancing communication strategies, which harness the patient's positive expectations whilst still giving truthful information, should be introduced into routine clinical practice starting with the acute pain service.⁴ Here we provide several examples of how this can be approached.

First, use of placebo effect enhancing communication can be readily applied to patients receiving patient-controlled analgesia (PCA) intravenous opioids. This therapy currently forms the mainstay of acute pain management for many hospitals worldwide owing to patient satisfaction, effectiveness, and simplicity. The potentially detrimental confluence of high frequency of use and the purposeful design wherein high doses of opioid can be self-administered presents PCA as a key area in which clinicians should focus their efforts. Placebo enhancing communication at the bedside can take the form of the clinician instructing the patient, ‘The medicine in this device (PCA opioid) is very powerful. Patients report that the paracetamol and the anti-inflammatory (if applicable) pain relieving medications you are already taking are very effective at dampening the sensations from where you had surgery, and you will only need to use the button machine if you cannot cope with any remaining sensations’.

Placebo effect enhancing communication can also be applied to provide benefit when prescribing oral opioids. An example includes typical instructions given after Caesarean section. The caregiver will inform the patient, ‘the combination of paracetamol and the anti-inflammatory pain reliever you are receiving is remarkably effective, so much so, they give you the bulk of the pain relief we can provide with medications. Most patients then find they can cope with any residual sensations. If however you find these sensations too much for you to deal with then you can ask for an additional narcotic medication (e.g. oxycodone immediate release)’.

Clinicians intending to use placebo enhancing communication strategies as given in these examples will achieve the greatest success by also addressing two areas. First, it is necessary to educate rounding clinicians on the difference between nociception (a sensation) and the pain experience (when nociception becomes unpleasant). Second, optimisation of evidence-based best practice for non-opioid therapeutic approaches to enable maximal dampening of nociception (e.g. neural block, non-steroidal anti-inflammatory drugs, cyclo-oxygenase-2 inhibitors) must be ensured.⁵

Nocebo effects, induced by negative expectations, have been shown to markedly increase the reporting of adverse side-effects. Nocebo, from the Latin for ‘I shall harm’, is not beneficial and needs to be avoided.⁶ Nocebo enhancing practices in pain management are often unintentional, but owing to their widespread (mis-)use, induce considerable sabotage of effective pain management. For example, referring to analgesics as ‘painkillers’ is a commonly encountered nocebo-enhancing mistake made by clinicians. Our medications are only rarely capable of eliminating pain, as implied by the use of the term ‘killer’. An expectation mismatch for the patient then results, and so increases the perceived side-effects because the medication did not work as expected. In a similar way, informing a post-surgical patient provided with PCA delivered opioids to expect: ‘to need to press the button for the pain every time you move’ will again enhance the expectation of a negative experience (pain) with the potential for reports of higher levels of pain and greater use of opioid medication.

Responding to the opioid epidemic with a simple curbing of all opioid use may have a detrimental effect of denying opioids to those who would otherwise achieve the intended benefits. Rather, clinicians must apply strategies allowing the two competing needs of safety and efficacy to be met. Granted, balancing these competing needs can be more challenging to introduce on a time and resource basis. However, patients expect their doctors to be their advocates for the best possible care.

What we have learnt from placebo research can provide us with an acceptable and easy-to-implement effective bedside strategy to curb opioid overuse, such that the recently highlighted significant rates of ongoing opioid use after even minor surgery, of up to 7% at 90 days,⁷ may well become a historical episode.

Declaration of interest

The authors declare that they have no conflicts of interest.