Low Dose Initiation of Buprenorphine: A Narrative Review and Practical Approach

Abstract

Low dose buprenorphine initiation, is an alternative method of initiating buprenorphine in which the starting dose is very low and gradually increased to therapeutic levels over a period of days. This method takes advantage of slow displacement of the full opioid agonist from mu-opioid receptors, avoiding the need for a person with opioid use disorder to experience opioid withdrawal symptoms before initiating buprenorphine, while also minimizing the risk of precipitated opioid withdrawal. With this initiation method, full opioid agonists can be continued as buprenorphine is initiated, expanding the population to which buprenorphine can be offered. To date, the literature on low dose initiation is primarily case-based but rapidly growing. While evidence emerges, guidance for the use of low dose initiation is clearly desired and urgently needed in the context of an increasingly risky and contaminated opioid drug supply, particularly with high potency synthetic opioids, driving overdose deaths. Despite limited evidence, several principles to guide low dose initiation have been identified including: (1) choosing the appropriate clinical situation, (2) initiating at a low buprenorphine dose, (3) titrating the buprenorphine dose gradually, (4) continuing the full opioid agonist even if it is nonmedical, (5) communicating clearly with frequent monitoring, (6) pausing or delaying buprenorphine dose changes if opioid withdrawal symptoms occur, and (7) prioritizing care coordination. We review a practical approach to low dose initiation in hospital-based and outpatient settings guided by the current evidence.

CDC Clinical Practice Guideline for Prescribing Opioids for Pain—United States, 2022

“…To do this, experts have advised that clinicians and patients should wait at least 8–12 hours after the last dose of short-acting full agonist opioids and longer after the last dose of long-acting full agonist opioids (e.g., at least 12–24 hours after the last dose of an ER/LA full agonist opioid, and longer for methadone) before the first dose of buprenorphine is administered ( 229 ). As an alternative for patients not yet in opioid withdrawal, certain studies have described low dose initiation of buprenorphine to allow for initiation of buprenorphine in patients receiving full agonist opioids for acute or chronic pain ( 241 ). SAMHSA’s Providers Clinical Support System ( https://pcssnow.org ) offers training, technical assistance, and mentors to assist clinicians who are unfamiliar with initiation of buprenorphine and have additional questions about the diagnosis and treatment of opioid use disorder.…”

Factors that distinguish opioid withdrawal during induction with buprenorphine microdosing: a configurational analysis

“…The buprenorphine microdosing method can be used as long as the basic principles are followed [ 1 ]. Until then, our analysis provides initial understanding of what pathways distinguish published cases with opioid withdrawal compared to published cases without withdrawal and is an update to existing evidence [ 1 , 4 , 25 , 38 – 40 ]. This insight can better inform provider discussions and patient understanding of expectations during the induction process.…”

Opioid withdrawal management in the fentanyl era

“…In the United States, short-acting opioids can be administered to hospitalized patients as an adjunct to medical or surgical care, and in Canada they may be used in both in-and outpatient settings [15,16]. They can be rapidly and safely titrated to therapeutic effect and can facilitate initiation of buprenorphine, methadone, slow-release oral morphine or other opioid agonists for maintenance treatment of opioid use disorder [17][18][19].…”