Over the past 10 years, rates of opioid-related overdose deaths and opioid-related harms have drastically increased in British Columbia [1]. Since 2015, illicit drug use has surpassed suicide as the major cause of unnatural deaths in BC, with fentanyl-related overdoses implicated as the leading cause of illicit drug overdoses [1]. This public health crisis of historical scale has taken more lives than the HIV epidemic in the early 1990′s [2]. The latter at its peak (1995) was identified as the cause of a total of 1764 mortalities in Canada [3] compared to 4588 reported apparent opioid-related deaths in Canada in 2018 [4] when, approximately four people lost their lives to overdose every day in BC [1].
Opioid agonist treatment (OAT) has been shown to reduce morbidity and mortality among patients with opioid use disorder (OUD) [5,6,7,8,9,10]. Buprenorphine/naloxone has become the recommended first-line OAT in Canada based on its preferable safety profile and efficacy [11, 12].
Buprenorphine is a partial μ agonist, with high receptor affinity resulting in a slow dissociation from the receptor and prolonged activity. Naloxone has minimal effect when taken orally and is introduced to the formula to minimize diversion. The pharmacokinetics of buprenorphine/naloxone result in a favourable safety profile due to a ceiling effect on respiratory depression and the ability for rapid titration. Precipitated withdrawal can result if buprenorphine/naloxone is introduced in the presence of other opiates with lesser-binding affinities, such as heroin or methadone; therefore, patients are required to be in moderate withdrawal prior to induction.
Need for withdrawal prior to induction is acknowledged as a challenge for choosing OAT with buprenorphine/naloxone (BUP/NLX). This requirement mandates the patients to time their withdrawal to match an office-based appointment, and to be supervised for several hours. This is a barrier for a variety of reasons, such as lack of clinic space or staffing to monitor the induction, and also patients’ anxiety, impulsivity, work or school commitments interfering with such a long stay in the clinic. In addition to the fluctuating level of consciousness associated with high opioid use, tolerating the high cravings to use during the timed withdrawal which is required for office induction is another inherent challenge for this method. While home BUP/NLX induction strategies have offered an alternative to the need for withdrawal in clinic, there remains a selected patient population for whom the requirement for moderate withdrawal prior to initiation will remain a barrier regardless of the setting [13, 14]. Patients may also be fearful of precipitated withdrawal, which is associated with usual induction starting before adequate withdrawal. Moreover, precipitated withdrawal is perceived by some providers a barrier for adopting home induction with buprenorphine [15]. These barriers may encourage patients towards other OAT medications with less favourable safety profile such as methadone or slow-release oral morphine. Microdosing inductions can preclude the requirement for the withdrawal prior to induction and also may decrease the risk of precipitated withdrawal. Ultimately, it will also provide patients keen on starting OAT with BUP/NLX with more options.
A microdosing schedule for buprenorphine was first introduced and trialed in 2010 by Hamming et al. in Bern, Switzerland [16], followed by a more recent report of two cases of successful induction of buprenorphine/naloxone in 2016 [17]. The first case was induction of buprenorphine/naloxone using a microdosing schedule starting at 0.2 mg daily and titrated up to 12 mg daily over 9 days, with gradual reduction and eventual cessation of illicit heroin use over this time [16]. The second case was a gradual cross-titration of methadone and diacetylmorphine to buprenorphine/naloxone starting at 0.2 mg and titrated up to 24 mg over 28 days [17]. Both patients tolerated this induction without reporting the experience of precipitated withdrawal or need for withdrawal from opiates prior to induction. This method has been coined “The Bernese Method” [16]. The pharmacological hypothesis tested in the Bernese Method is that small amounts of buprenorphine doses should not precipitate opioid withdrawal, but because of its relatively long half-life, accumulates at the receptor gradually replacing the full μ-agonist (e.g. fentanyl, heroin) at the opioid receptor. This was successfully shown with these two cases presented by Hamming; however, this has not been replicated in the current practice literature [16, 17].
There has been growing interest in the Bernese Method in Vancouver, BC, Canada, as healthcare providers struggle to find ways to reduce mortality in the context of a public health emergency. To date, there has been considerable effort to engage individuals who use opioids in opioid agonist treatment, as well as to provide overdose response kits and personnel to manage acute overdoses [18]. The Bernese Method is a potential compliment to patients who want treatment with buprenorphine/naloxone, but are adverse to the traditional induction method because of the need for withdrawal and/or have difficulty attending scheduled appointments. This method has also shown promise for other indications such as pain management [19].
Apart from above-mentioned barriers, there remains other challenges for home induction with BUP/NLX. Home induction works best for patients who have stable housing, relatively good cognitive function, and are organized enough to reliably follow instructions. Unfortunately, this is not the case for most of patients who are served by the outreach programs, patients with severe opioid use disorder, high rates of cognitive impairment and major mental health illness in the most vulnerable opioid using population i.e. homeless population that can interfere with their ability to come to a clinic, tolerate withdrawal, and stay for induction and as a result precludes them often from successful home induction. Provision of microdosing within an outreach program can make buprenorphine/naloxone treatment accessible to high-risk patients who have difficulty attending office-based appointments or complying with a home-based protocol. Assertive outreach, part of this model of care, involves flexible delivery of integrated health services by an interdisciplinary team and is an established model for engaging patients with complex needs that have not been met in traditional office-based settings [20, 21]. The Inner City Youth Program (ICYP) uses this approach with high-risk youth who are living with moderate to severe mental illness and/or substance use disorders, and psychosocial and/or medical complexities. The ICYP is located at Foundry Vancouver Granville, which is a “one-stop shop” health centre in downtown Vancouver for young people aged 12–24, which includes support to family members and caregivers. Care is provided by an interdisciplinary team of peers and professionals through clinic-based and outreach services.
In February 2018, we began using a microdosing regimen to initiate regular dosing of buprenorphine/naloxone in ICYP patients with significant barriers to induction, such as developmental disabilities, homelessness, and psychosis. We used assertive outreach to identify and locate patients with OUD who were not receiving OAT and offer them buprenorphine/naloxone microdosing induction on the spot. OAT prescribers offered weekly outreach, and interdisciplinary team members provided case management and supported patients with their OAT and other related goals. Patients were linked to primary care, psychiatry, peer support and other services.
In the first 6 months of this program, 14 people, 18–25 years-old with severe disordered use of multiple substances and comorbid mental illness, and history of residential instability and poverty were engaged in care with 8 successful inductions and no instances of precipitated withdrawal. This method has also attracted growing interest among other clinics in our community. As there are limited published reports on this topic, we present a case report for discussion to contribute to the body of evidence. Specifically, we present a case of a patient successfully completing buprenorphine/naloxone induction, without reporting a period of withdrawal, using a microdosing schedule delivered via assertive outreach. Success was defined as reaching a therapeutic dose of Suboxone for a minimum of 30 consecutive days.