The Pharmacology of Buprenorphine Microinduction for Opioid Use Disorder

Abstract

Although expanding the availability of buprenorphine—a first-line pharmacotherapy for opioid-use disorder (OUD)—has increased the capacity of healthcare systems to offer treatment, starting this medication is fraught with significant barriers. Standard induction regimens require persons with OUD to taper and discontinue full opioid agonists and experience opioid withdrawal prior to the first dose of buprenorphine. Further, emerging evidence indicates that precipitated withdrawal during induction may impact long-term treatment outcomes. Microinduction is a novel approach that, by harnessing buprenorphine’s unique pharmacological profile, may allow circumventing the needed for prolonged opioid tapers, and reduce the risk of precipitated withdrawal—holding promise to enhance treatment access. In this review, we examine the pharmacological basis for microinduction and appraise the evidence of this approach to improve clinical outcomes among persons with OUD. First, we highlight the potential dose-dependent effects of buprenorphine on two key neuroadaptations at the mu-opioid receptor (MOR)—resensitization and upregulation. We then focus on how microinduction may reverse these chronic MOR neuroadaptations, allowing the maintenance of an adequate opioid tone, and thereby potentially circumventing opioid withdrawal. Second, we describe the clinical evidence available, derived from observational reports and open-label studies, examining the potential efficacy of microinduction. Despite significant heterogeneity—exemplified by variable buprenorphine formulations, daily doses, and schedules of administration—these data provide preliminary support for the feasibility of microinduction. Finally, we provide new mechanistic, methodological, and clinical insights to guide future translational research, as well as randomized, placebo-controlled clinical trials in this compelling agenda of pharmacotherapy development.

Synergistic Effect of Ketamine and Buprenorphine Observed in the Treatment of Buprenorphine Precipitated Opioid Withdrawal in a Patient With Fentanyl Use

“…The patient reported recently engaging in telehealth OUD treatment with a low-dose, cross-taper buprenorphine induction plan. 6 (Table 1). On day 7, the patient took 12 mg SL buprenorphine at 10 AM, as planned, about12 hours after his last fentanyl use.…”

“…4,5 BPOW is an unpleasant physical and psychological experience sometimes observed in physically-dependent patients who have recently taken full-agonist opioids and are then administered buprenorphine. 2,6 It is generally believed that BPOW results from abrupt displacement of residual full agonist opioid from mu-opioid receptors (μORs) by buprenorphine, which binds tightly to μORs but with low intrinsic efficacy, causing a sudden drop in opioid activation that is experienced as withdrawal with rhinorrhea, body aches, anxiety, diaphoresis, tremor, tachycardia, and hypertension. 6 The intensity of BPOW can range from mild to life-threatening.…”

“…2,6 It is generally believed that BPOW results from abrupt displacement of residual full agonist opioid from mu-opioid receptors (μORs) by buprenorphine, which binds tightly to μORs but with low intrinsic efficacy, causing a sudden drop in opioid activation that is experienced as withdrawal with rhinorrhea, body aches, anxiety, diaphoresis, tremor, tachycardia, and hypertension. 6 The intensity of BPOW can range from mild to life-threatening. 1,7 Current guidelines recommend that to prevent BPOW, buprenorphine treatment for OUD should be started with a multi-day induction procedure.…”

Microdosing Transdermal Buprenorphine to Transition a Patient off a Higher-Dose Methadone Regimen

“…14,16 Others have described discontinuing methadone and bridging with a short acting opioid such as morphine or fentanyl patches. 15 Here, we present a case of transitioning a patient taking a high dose methadone regimen to buprenorphine using a transdermal microdosing protocol [18][19][20] with an as needed full opioid agonist, hydromorphone, that did not require methadone dose tapering prior to initiation and avoided symptoms of opioid withdrawal.…”

Buprenorphine Microinduction: Logistical Barriers and the Need for Convergent Evidence

“…Dear Editor, We thank Dr. Accurso for his interesting report on the clinical use of buprenorphine microinduction [1]. We agree that there are logistical barriers that contribute to the difficulty in implementing microinduction, especially in primary-care settings [2,3]. First, healthcare professionals must write complex orders, with progressive increases in the dose of buprenorphine, as well as frequent changes in its schedule of administration.…”