REVIEW OF: Antoine D et al, Am J Addict 2021;30(1):83–87

The escalating rate of opioid overdose deaths has been linked to the rise of illicit fentanyl. Increasing evidence shows that fentanyl and its analogues, such as carfentanil and acetylfentanyl, are fast replacing heroin as the most commonly used illicit opioid for many people with opioid use disorder (OUD). Furthermore, fentanyl has become a common adulterant of many street drugs, meaning it is often used inadvertently with potentially lethal results.

The widespread availability of fentanyl has changed the landscape of opioid treatment, because its pharmacologic properties differ from other opioid agonists. In particular, fentanyl’s lipophilicity, rapid crossing of the blood-brain barrier, and sky-high receptor potency can make for tricky buprenorphine induction.

The usual method of buprenorphine induction consists of waiting for the patient to develop moderate withdrawal symptoms, then giving a 2–4 mg dose of sublingual buprenorphine and possibly repeating the dose after a few hours. This works well for most opioids; however, evidence indicates that patients are more likely to suffer precipitated withdrawal from this protocol if they have fentanyl in their system. In addition, “fentanyl” from the street can actually consist of a mixture of fentanyl, various fentanyl analogs, and other opioid agonists, further complicating the picture.

Realizing that precipitated withdrawal could deter people from seeking treatment, the authors set out to investigate whether frequent small doses of buprenorphine initiated at higher Clinical Opiate Withdrawal Scale (COWS) scores resulted in fewer precipitated withdrawal symptoms than the usual induction procedure.

Researchers recruited four participants who had recently used fentanyl but had been abstinent for 24 hours. Two patients underwent induction using the standard procedure: 4 mg of buprenorphine once COWS reached 9, followed by another dose three hours later. The other two patients underwent the novel induction strategy: 2 mg of buprenorphine at COWS of 13, followed by additional 2 mg doses at 1.5, 3.5, and six hours.

The researchers found that the patients who underwent the standard buprenorphine induction had severe precipitated withdrawal (defined as COWS > 12). One patient even had COWS above 30 shortly after receiving the first dose of buprenorphine. The patients who received the modified induction never scored above 10 once buprenorphine was initiated.

This study adds to growing evidence that lower initial doses of buprenorphine can ease the induction process. In a prior issue of CATR (November/December 2020), and in the research update on the previous page, we discussed microinduction, in which very low doses of buprenorphine are used to allow patients to start buprenorphine without having to go into withdrawal first. The dosing strategy being studied here is different, in that patients experience withdrawal prior to induction and the dose being utilized (2 mg) lies somewhere between microdosing (0.5 mg) and the standard induction protocol (4–8 mg).

CATR’S Take
This was only a small case series, but the strategy may be worth trying for your patients using fentanyl, especially if they have a history of precipitated withdrawal when initiating buprenorphine.