Why Tapering Presents a Conundrum

A recent article by Manhapra et al. highlights challenges related to the mechanism of opioids' benefit for pain, and from the neuroplastic and behavioral adaptations that emerge, to varying degrees across patients, as a result of long-term opioid therapy.^{Reference Manhapra, Arias and Ballantyne32} The briefest possible summary takes note of the following. Pain is not just a nociceptive experience, but an affective state in which pain and its relief are modified by learning, memory and behavior. Each of these, one might add, are influenced by life history, the clinical care context, and, in ways that are still subject to debate, the perpetuation of whatever injuries generated the pain in the first place.

Opioids' admittedly uneven benefit in long-term pain depends not just on interrupting pain signals (antinociception) impacts but on affective and emotional relief (i.e. interaction with brain reward systems), as well as expectancies associated with taking medicine. Evidence on opioid utility is mixed. Opioids show small benefits compared to placebo in studies of three to six months' duration,^{Reference Meske, Lawal, Elder, Langberg, Paillard and Katz33} and similar (and small) average benefits as non-opioid treatments.^{Reference Busse, Wang, Kamaleldin, Craigie, Riva, Montoya and Mulla34} A one-year trial compared aggressive opioid dose escalation to a stepwise series of non-opioid therapies, with a low-potency opioid being the final step (and required by only a small number of patients). Both trial arms obtained similarly good outcomes.^{Reference Krebs, Gravely, Nugent, Jensen, DeRonne, Goldsmith, Kroenke, Bair and Noorbaloochi35} Long-term continuation at low dose without obvious adverse effect is observed in some selected adult populations.^{Reference Cheatle, Gallagher and O'Brien36} However, the downside of repeated opioid use is, crucially, not limited to physiologic tolerance or the potential for acute opioid withdrawal syndrome, which manifests with a myriad of symptoms (i.e. diarrhea, sweats, anxiety) when opioid medications are stopped quickly.

A greater challenge is physical and psychologic dependence on the opioid. Dependence is a complex neuro-adaptive change involving multiple neurologic substrates and mechanisms, not all of which are covered here. One of cardinal interest, however, is the “opponent process,” which derives from psychological literature.^{Reference Ballantyne, Sullivan and Kolodny38} An opponent process is a normal psychological phenomenon that tends to “push back” against reward or relief experiences.

The power of this opponent process is likely to differ greatly across situations and people. But we reason that it tends to grow more pronounced after repeated exposure to a rewarding/relieving stimulus, such as pain relief from an opioid dose. As a result, net relief tends to diminish over time and the overall pain experience can worsen, independent of the primary pathology that created the pain, even if each dose is still experienced as helpful to the individual.

The term “dependence” indicates that the patient reaches a new steady-state (termed “allostatic reset”). On its face, that steady-state may look good (i.e. patient takes medication and functions well in life), or it may look bad (in the extreme, addiction). Somewhere between these poles, some patients have formed a dependence in which the pain, emotions and energy levels are volatile, but the opioids are experienced as helpful anyway. The heuristic expression “complex persistent dependence” has been applied to this situation.^{Reference Ballantyne, Sullivan and Kolodny38} Opioid discontinuation and dose reduction among patients with complex persistent opioid dependence can cause several effects beyond the acute physical withdrawal that most people know about. After dose reduction, a more protracted opioid withdrawal syndrome can transpire, with a complex presentation, of which many clinicians are unaware. This more complex clinical presentation may include sustained worsening of pain (i.e. rebound) and function, psychiatric instability, aberrant behaviors in relation to the prescribers and clinical caregivers, emergence of new substance use disorder, and medical destabilization.³⁹

A taper of dose (MME) for a prescription opioid seems intuitively appealing from a clinical perspective, especially in the setting of problematic opioid dependence, save for two underestimated issues:

First, opioids may still represent the only operational, effective treatment for assuring reasonable function among those with severe long-term pain. Many alternatives pose less risk, to be sure. The one-year trial, mentioned above, found that aggressive use of opioids was not superior to a careful and systematic opioid-avoidant strategy in which a low-potency opioid (tramadol) was held in reserve, for a few.⁴⁰ But that trial did not purport to represent the full spectrum of human conditions involving severe pain, and it relied on people who volunteered to be randomized. Additionally, among non-opioid treatments, a summary by the US Agency for Healthcare Research and Quality found that most showed small average benefits, in trials of short duration, demonstrating efficacy for only some patients, not all.^{Reference Skelly, Chou, Dettori, Turner, Friedly, Rundell and Fu41} Finally, many helpful behavioral interventions, such as yoga, are not easily accessed by people contending with geographic distance, payment barriers, and full time jobs.^{Reference Chang and Kertesz42}

The second issue is the as-yet unresolved evidentiary debate on taper, which governs the following two sections.

Tapering: Introducing the Arguments

In considering taper, a metric of success is required. In understanding the conflict between institutional actors (e.g. regulators, payers) and patients, it is crucial to describe the difference between regulatory definitions of success and clinical definitions of success.

For institutional voices such as the Office of the Inspector General for the US Department of Health and Human Services,⁴³ the National Committee for Quality Assurance,⁴⁴ and other actors, reducing the number of persons at “high amounts” of opioids (i.e. >90 or >120 MME) defines success. That reduction alone permits institutions to document good faith in confronting a societal crisis, and also to contain political or legal vulnerability.

For clinicians, however, success has to involve patient well-being. In general, an opioid taper can be considered successful only if the probable risk improvement with dose reduction can be balanced with the degree of achievement of goals that are important to patient, namely, stability or improvement in pain and function, avoiding instability and harm related to medical, psychiatric, and psychological conditions.⁴⁵ And, with the recognition of protracted opioid withdrawal syndrome as a serious adverse effect, successful taper should also avoid significant protracted abstinence syndrome.

Thus, the evidentiary argument reviewed here will focus on success and failure from a clinical perspective, returning to the issue of ethical imperatives only in closing.

Ethical Considerations

The push to taper opioids in patients who receive these medicines long-term for care of pain occurs in the context of a complex a social tragedy of addiction. In that context, institutional actors, leaders and clinicians are under pressure to show evidence of good faith in attempting to correct prescribing practices that contributed to the genesis of the crisis itself. In turn, payers, regulators, lawmakers, and others have created strong incentives or mandates on prescribers and patients in the form of payment policies, legal restrictions, and quality of care metrics that treat the opioid dose received as bad if it sits above a given level. Such policy initiatives incentivize taper and discontinuation, with or without the patient's consent.

And yet the evidence to favor forced or mandated dose reduction remains weak since existing studies favorable to taper involve voluntary patients working with experts, and a body of observational data has emerged to suggest that outcomes after opioid stoppage are often poor.

For institutions tracking prescription changes, however, the metrics of achievement are aggregate in nature and focused on patient panels (i.e. “percentage of patients receiving high dose”), and appear to be in serious tension with metrics focused on individual well-being and health. This emphasis on the aggregate tends to be the case for institutional actors regardless of whether their leaders are motivated by altruism or simple desire to reduce adverse attention. An emphasis on maximizing a perceived aggregate good for the most persons is, traditionally, aligned with utilitarianism.^{Reference Weiss, Potter, Fiellin, Byrne, Connery, Dickinson and Gardin64} However, we have not seen health care institutions declare a willingness to harm some patients in order to advance a perceived health care benefit for others. Thus, even if some quality metrics and strategies appear utilitarian on their face, underlying commitments of institutional leaders in health care, quality measurement or regulatory offices are not likely to be entirely so.

The ethical situation for prescribers is clearer. A doctor is expected to focus on optimizing benefit for each patient as an individual. In that fiduciary relationship, the provider is trained never to treat a patient merely as a means to an end (and in this situation, optimizing a population metric would be one example), but as an end in himself or herself, an echo of one of the categorical imperatives first laid out by Kant.^{Reference Bentham and Mill65} If a prescriber adheres to institutional pressure to reduce dose despite sincere concern that doing so harms the patient, it is clearly unethical for the provider.

When these conflicts emerge in health care, they have been termed a problem of a dual agency.^{Reference Kant and Ellington66} To uphold the interests of institutions (many of which have power over the physician's livelihood, at least indirectly), prescribers should cut prescriptions, effectively acting as agent for those institutions. Certainly, they are under forms of pressure to do so, most notably through payment controls, quality metrics, risk of legal investigation, and governmental rules. Perspectives on how physicians should generally handle dual agency have often arisen in the context of whether to offer potentially costly services to an individual, when doing so might affect the fiscal stability of the payer. In that context, there is ample room for dispute.

In this case, however, one cardinal principle can guide us. A general injunction against harming patients makes a generalized policy of forced opioid taper problematic, if death or debility number among the potential outcomes. Naturally, a principle of “do no harm” could also justify scrutinizing ongoing prescriptions with a level of concern, given that such data as exist for opioid-related benefit cannot be divorced from consideration of opioid-related harm. That may justify attempted taper, if the clinician can assure a level of support and follow-up that would allow protection against harm and reversal of course if harm emerges. However, actions that risk grievous harm to patients, including death, in favor of institutional perceptions of an “aggregate good” are hard to justify.

In sum, clinicians who care for patients receiving opioids face an ethical problem in regard to tapering incentivized or mandated by agencies that deliver, regulate and otherwise govern health care. It is a problem of dual agency, of being pulled between a regulatory definition of success in addressing a national opioid crisis and a clinical definition of success in caring for patients. For institutional actors, reducing high-dose prescriptions has proven a compelling objective, despite warnings from several federal agencies that not all opioid reductions are necessary or protective. Clinicians seeking to uphold a primary fiduciary duty to each patient as an individual are likely to find that their actions are often in tension with the agencies that pay, regulate, measure, and govern them, until there is greater agreement about how success is defined in the care of a vulnerable patient population.