Best Practice of the Month

Low-dose Buprenorphine Initiation: What, Where, Why, How, and For Whom?

What is low-dose initiation?

Low-dose initiation (sometimes referred to as “microdosing”) is an alternative buprenorphine initiation approach in which an individual takes very low buprenorphine doses, which are titrated up to therapeutic levels over the course of multiple days. With this initiation method, full opioid agonists (including nonpharmaceutical opioids) can be continued as buprenorphine is initiated and titrated up. These small doses of buprenorphine will very slowly displace the full opioid agonist, which minimizes opioid withdrawal symptoms and avoids precipitated withdrawal.²

Where can low-dose initiation be offered?

Low-dose initiation can be offered in inpatient and outpatient settings.^2,3

Why offer low-dose initiation?

This approach avoids the need for an individual to be in opioid withdrawal prior to initiating buprenorphine and also minimizes the risk of precipitated withdrawal symptoms. Published data describing the frequency of buprenorphine-precipitated withdrawal in the era of a predominantly illicitly manufactured fentanyl supply are limited, but a recent study found that only 1 percent of patients initiated on buprenorphine in 28 U.S. emergency departments experienced precipitated withdrawal, despite high prevalence of fentanyl use.[i] However, fear and distress associated with opioid withdrawal can be a barrier for patients considering buprenorphine, so low-dose initiation can be a good alternative for some patients.³

How do you prescribe a low-dose initiation?

Multiple protocols exist, and most vary from 3– 7-day overlap initiation protocols, meaning buprenorphine is initiated while the individual continues to use other opioids (including nonpharmaceutical opioids). This resource from CA Bridge describes 3- and 7-day cross-taper dosing schedules (see page 2), and this resource from New York State Office of Addiction Services and Supports PDF provides a summary of 2 different outpatient protocols for low-dose buprenorphine initiation (see page 8). Note that both resources provide dosing protocols utilizing the buprenorphine transdermal patch; however, the buprenorphine patch is not Food and Drug Administration approved for the treatment of OUD and, therefore, is not legal to use for OUD treatment in the outpatient setting. Consequently, in the outpatient setting, film or tablet splitting is the most accessible and cost-effective method.²

For whom would you recommend low-dose initiation?

Traditional buprenorphine initiation remains the clinical standard of care in most settings, but low-dose initiation can be particularly helpful when a patient has intolerance to withdrawal, and/or past buprenorphine initiation attempts have precipitated withdrawal. Low-dose initiation can be offered to any patient, but it is important to note that this approach requires daily dose changes and typically requires splitting films or tablets, which can be confusing. For this reason, the following considerations for outpatient settings are recommended: ²

• Provide clear instructions with daily or near-daily check-ins with a member of the health care team
• Provide a patient dosing guide/handout
• If possible, partner with a pharmacy to provide a blister pack to help with a dosing schedule

A recent, retrospective, outpatient case series reported on the outcomes of 12 patients who were prescribed a low-dose buprenorphine initiation using a 3-4 day overlap protocol. Eleven patients (92 percent) picked up their prescription; 7 (58 percent) returned for follow-up; and, of those, only 1 reported any withdrawal symptoms, which were mild.³

In conclusion, low-dose buprenorphine initiation is an alternative to traditional dosing that minimizes risk of precipitated withdrawal and reduces opioid withdrawal symptoms. Although dosing can be confusing for patients, this can be mitigated through patient education, handouts, frequent check-ins, and pharmacy supports.