Novel Induction to Buprenorphine/Naloxone: A Quasi-Experimental Study With Comparison Group

Medication for OUD (MOUD) is a first-line treatment for OUD and improves outcomes in mortality, retention in treatment, and non-prescribed opioid use. Buprenorphine/naloxone is the only MOUD of the three FDA-approved medications for OUD available in the telehealth setting, as methadone and injectable naltrexone must be managed in an in-person setting. Buprenorphine/naloxone, also referred to as brand name Suboxone, is administered by placing a film strip under the tongue. Buprenorphine acts as a partial agonist with a high binding affinity at the mu-opioid receptor; clearance of the pure opioid agonist must occur before a full dose of buprenorphine is administered, as buprenorphine will displace opioid agonists with lower binding affinity at the receptor and cause rapid-onset "precipitated withdrawal." During traditional induction, patients must abstain from opioids prior to starting buprenorphine/naloxone and thus endure mild-to-moderate opioid withdrawal before initiating buprenorphine (to avoid precipitated withdrawal). Barriers to traditional induction include the required withdrawal period, fear of precipitated withdrawal (particularly with increased fentanyl in the opioid supply, which is lipophilic and thus remains in the body longer after last use), and an intolerable withdrawal period (which increases the risk of a patient leaving treatment to return to non-prescribed opioid use). In addition, there are patients who are not ready to stop their opioid but are ready to start treatment.

First described in the literature as the Bernese Method in 2016, microdosing induction was developed to overcome these barriers. Microdosing induction requires the administration of small but escalating doses of buprenorphine/naloxone over a period of several days to weeks, such that the buprenorphine slowly overcomes the effect of the opioid agonist at the receptor. This technique does not require a period of withdrawal prior to starting treatment. Various microdosing induction protocols have been described primarily in inpatient settings in case reports, case series, and literature reviews. No published research studies exist that systematically evaluate the effectiveness and safety of microdosing induction, particularly in a telehealth setting.

Using a quasi-experimental design for evaluating MOUD induction strategies in a telehealth setting, the investigators will estimate the effect of microdosing induction on patient completion of successful induction with mild withdrawal, adjusted maximum withdrawal score, and adverse events. The investigators hypothesize that microdosing induction patients will have higher odds of completing a successful induction with mild withdrawal, lower maximum withdrawal scores, and a similar number of adverse events compared to traditional induction patients.

Study Details:

The proposed study will follow a quasi-experimental design with a comparison group to evaluate the effectiveness and safety of microdosing induction versus traditional induction of buprenorphine/naloxone in telehealth patients at Bicycle Health. Bicycle Health is a digital health company that provides biopsychosocial treatment of OUD via telehealth. With guidance from the research team, participating medical providers at Bicycle Health will recruit patients at intake who meet eligibility criteria (see Participant Population section below). Based on sample size calculations under different scenarios, and feasibility given current intake rates at Bicycle Health, the study will enroll at least 85 patients in the microdosing induction group, and at least 85 patients in the comparison group.