Understanding Buprenorphine for Use in Chronic Pain: Expert Opinion

Abstract

Objective: An expert panel convened to reach a consensus on common misconceptions surrounding buprenorphine, a Schedule III partial µ-opioid receptor agonist indicated for chronic pain. The panel also provided clinical recommendations on the appropriate use of buprenorphine and conversion strategies for switching to buprenorphine from a full µ-opioid receptor agonist for chronic pain management.

Methods: The consensus panel met on March 25, 2019, to discuss relevant literature and provide recommendations on interpreting buprenorphine as a partial µ-opioid receptor agonist, prescribing buprenorphine before some Schedule II, III, or IV options, perioperative/trauma management of patients taking buprenorphine, and converting patients from a full µ-opioid receptor agonist to buprenorphine.

Results: The panel recommended that buprenorphine's classification as a partial µ-opioid receptor agonist not be clinically translated to mean partial analgesic efficacy. The panel also recommended that buprenorphine be considered before some Schedule II, III, or IV opioids in patients with a favorable risk/benefit profile on the basis of metabolic factors, abuse potential, and tolerability and that buprenorphine be continued during the perioperative/trauma period. In addition, switching patients from a full µ-opioid receptor agonist to buprenorphine should be considered with no weaning period at starting doses that are based on the previous opioid dose.

Conclusions: These recommendations provide a framework for clinicians to address most clinical scenarios regarding buprenorphine use. The overall consensus of the panel was that buprenorphine is a unique Schedule III opioid with favorable pharmacologic properties and a safety profile that may be desirable for chronic pain management.

Keywords: Buprenorphine; Chronic Pain; Opioid; Partial Agonist; Schedule III; µ-Opioid Receptor.

Figure 1

The history of buprenorphine. Buprenorphine was originally developed as an analgesic and was subsequently used for OUD before novel delivery systems allowed for approval in chronic pain management [8,9,12,13]. FDA=Food and Drug Administration; OUD=opioid use disorder.

Figure 2

Receptor/ligand definitions and applications to buprenorphine at the μ-opioid receptor. *Definition of a partial agonist: a compound with an intermediate intrinsic activity that at full receptor saturation produces less than the maximal effect obtainable with full agonists in some specified set of in vitro or clinical circumstances [25]. Buprenorphine is a potent Schedule III opioid with high binding affinity at the μ-opioid receptor that behaves as a partial agonist on the basis of in vitro studies [7,14,26]. Although buprenorphine has less total intrinsic activity (capacity to activate a receptor to induce multiple signaling pathways) than full μ-opioid receptor agonists, it still effectively stimulates the analgesic signaling pathway from the μ-opioid receptor [7,14,25,27,28]. 3D=three-dimensional; OR=opioid receptor.

Figure 3

Efficacy and tolerability of buprenorphine compared with those of other opioids used for chronic pain. (A) Potential mechanism of action for buprenorphine and (B) conceptual representation of possible effects compared with those of Schedule II opioids such as, but not limited to, fentanyl [33,38,39]. OR=opioid receptor; ORL1=opioid receptor-like 1.