To the Editor: We thank Dr. Tiemstra for the overview of common questions about medication for opioid use disorder (MOUD) and appreciate that the format was intended to give family physicians confidence when treating patients with OUD.¹ We strongly agree that offering MOUD in the primary care setting is critical to increasing access to this lifesaving treatment. Given the changing landscape of nonprescription opioids being consumed by our patients, we propose that the induction technique described as “the standard approach” should be one among several options for patients to initiate buprenorphine in the era of fentanyl.

The article states that opioids should be stopped 12 to 24 hours before buprenorphine induction, and the patient should be in mild opioid withdrawal as measured by the Clinical Opiate Withdrawal Scale (COWS). This typically is an effective strategy for patients transitioning from heroin or other short-acting opioids, such as prescription hydrocodone. Unfortunately, patients using fentanyl may experience buprenorphine-precipitated withdrawal even after prolonged abstinence, with a mean clearance of active metabolites of 13.3 days.² Many patients relapse on fentanyl before transitioning to buprenorphine because they cannot tolerate the prolonged withdrawal. Also, the standard approach may result in precipitated withdrawal and loss to follow-up.

Use of low-dose buprenorphine induction (LDBI) protocols can be helpful in these cases.³ LDBI uses very small doses of buprenorphine with gradual dose increases over days to weeks.⁴ The patient does not need to cease opioid use before induction, and the small amounts of buprenorphine do not cause precipitated withdrawal. The off-label use of injectable buprenorphine similarly increases serum buprenorphine concentration slowly over days and is currently being studied in rapid induction protocols.⁵

Another tool not discussed explicitly in the article is home induction using the Subjective Opiate Withdrawal Scale with LDBI or the standard approach.⁶ Home induction is especially helpful when the timing of opioid cessation and induction with buprenorphine is difficult to arrange within clinic hours in the outpatient setting. Adjunctive medications targeting common withdrawal symptoms, including anxiety, tachycardia, myalgia and arthralgia, diarrhea, nausea, and insomnia, can be useful and are likely familiar to many family physicians. The use of hydroxyzine, clonidine, ibuprofen, loperamide, ondansetron, trazodone, and cyclobenzaprine can ease the discomfort of withdrawal, which increases the likelihood of induction success.

We very much agree that these treatments are changing the lives of patients. We hope more family physicians will join us in caring for people with OUD.

In Reply: I agree that a patient's treatment initiation will be most successful when tailored to their specific situation and preferences, and that the opioids they are currently using should be part of that consideration.

The risk of precipitated withdrawal certainly increases with fentanyl, but clinical data so far are reassuring. Three studies of high-dose buprenorphine administered in the emergency department reported rates of precipitated withdrawal in patients testing positive for fentanyl of 1%, 4.5%, and 2.6%, with only two patients requiring admission.^1–3 These studies also demonstrate that opioid clearance from the urine before buprenorphine dosing is not required to prevent precipitated withdrawal. High-dose initiation is emerging as a safe and efficient strategy in outpatient settings, reducing the amount of time patients may experience withdrawal symptoms during initial dose titration. In the office setting, most patients can be instructed on the timing of the first dose and safely initiate buprenorphine at home. Patients with high risk, such as those using fentanyl, may come to the clinic for an observed initial dose and/or be given a short-acting opioid for a few days after stopping fentanyl before starting buprenorphine. LDBI was developed for patients transitioning from methadone to buprenorphine in the inpatient setting.⁴ LDBI requires frequent dosing, clinical assessment, and dosing changes, making it more challenging for outpatient use.

Several validated scales are available to clinicians and researchers to identify stages of withdrawal in a consistent manner, including COWS, Objective Opiate Withdrawal Scale, Subjective Opiate Withdrawal Scale, Short Opiate Withdrawal Scale of Gossop, and Clinical Institute Narcotic Assessment. The COWS was developed using features of earlier scales to be relatively quick to administer while accurately discriminating between mild, moderate, moderately severe, and severe withdrawal. The COWS has been widely accepted because it is relatively easy to use for both clinicians and patients. There are no outcomes data suggesting any scale is superior, so the choice can be based on clinician preference.^5,6

Adjunctive medications can make withdrawal more manageable, but in the setting of buprenorphine initiation, the first answer is to increase the dose of buprenorphine.