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Objectives:Patients with opioid use disorder (OUD) can initiate buprenorphine without requiring a withdrawal period through a low-dose (sometimes referred to as “micro-induction”) approach. Although there is growing interest in low-dose buprenorphine initiation, current evidence is limited to case reports and small case series.Methods:We performed a retrospective cohort study of patients with OUD seen by a hospital-based addiction medicine consult service who underwent low-dose buprenorphine initiation starting during hospital admission. We then integrated our practice-based experiences with results from the existing literature to create practice considerations.Results:Sixty-eight individuals underwent 72 low-dose buprenorphine initiations between July 2019 and July 2020. Reasons for low-dose versus standard buprenorphine initiation included co-occurring pain (91.7%), patient anxiety around the possibility of withdrawal (69.4%), history of precipitated withdrawal (9.7%), opioid withdrawal intolerance (6.9%), and other reason/not specified (18.1%). Of the 72 low-dose buprenorphine initiations, 50 (69.4%) were completed in the hospital, 9 (12.5%) transitioned to complete as an outpatient, and 13 (18.1%) were terminated early. We apply our experiences and findings from literature to recommendations for varied clinical scenarios, including acute illness, co-occurring pain, opioid withdrawal intolerance, transition from high dose methadone to buprenorphine, history of precipitated withdrawal, and rapid hospital discharge. We share a standard low-dose initiation protocol with potential modifications based on above scenarios.Conclusions:Low-dose buprenorphine initiation offers a well-tolerated and versatile approach for hospitalized patients with OUD. We share lessons from our experiences and the literature, and provide practical considerations for providers.

Selenium (Se) and vitamin E are antioxidant micronutrients. Se functions through selenoproteins and vitamin E reacts with oxidizing molecules in membranes. The relationship of these micronutrients with the Nrf2-antioxidant response element (ARE) pathway was investigated using ARE-reporter mice and Nrf2-/- mice. Weanling males were fed Se-deficient (0 Se), vitamin E-deficient (0 E), or control diet for 16 or 22 weeks. The ARE reporter was elevated 450-fold in 0 Se liver but was not elevated in 0 E liver. Antioxidant enzymes induced by Nrf2-ARE (glutathione S-transferase (GST), NAD(P)H quinone oxidoreductase (NQOR), and heme oxygenase-1 (HO-1)) were elevated in 0 Se livers but not in 0 E livers. Deletion of Nrf2 had varying effects on the inductions, with GST induction being abolished by it but induction of NQOR and HO-1 still occurring. Thus, Se deficiency, but not vitamin E deficiency, induces a number of enzymes that protect against oxidative stress and modify xenobiotic metabolism through Nrf2-ARE and other stress-response pathways. We conclude that Se deficiency causes cytosolic oxidative stress but that vitamin E deficiency does not. This suggests that the oxidant defense mechanisms in which these antioxidant nutrients function are independent of one another.

Low dose buprenorphine initiation, is an alternative method of initiating buprenorphine in which the starting dose is very low and gradually increased to therapeutic levels over a period of days. This method takes advantage of slow displacement of the full opioid agonist from mu-opioid receptors, avoiding the need for a person with opioid use disorder to experience opioid withdrawal symptoms before initiating buprenorphine, while also minimizing the risk of precipitated opioid withdrawal. With this initiation method, full opioid agonists can be continued as buprenorphine is initiated, expanding the population to which buprenorphine can be offered. To date, the literature on low dose initiation is primarily case-based but rapidly growing. While evidence emerges, guidance for the use of low dose initiation is clearly desired and urgently needed in the context of an increasingly risky and contaminated opioid drug supply, particularly with high potency synthetic opioids, driving overdose deaths. Despite limited evidence, several principles to guide low dose initiation have been identified including: (1) choosing the appropriate clinical situation, (2) initiating at a low buprenorphine dose, (3) titrating the buprenorphine dose gradually, (4) continuing the full opioid agonist even if it is nonmedical, (5) communicating clearly with frequent monitoring, (6) pausing or delaying buprenorphine dose changes if opioid withdrawal symptoms occur, and (7) prioritizing care coordination. We review a practical approach to low dose initiation in hospital-based and outpatient settings guided by the current evidence.

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Background In the United States, methadone for opioid use disorder (OUD) is highly regulated. Federal agencies announced guidelines in March 2020 allowing for relaxation of take-home methadone dispensing at opioid treatment programs (OTPs) to improve treatment access and reduce COVID-19 transmission risk during the public health emergency. We explored patient perspectives at three OTPs serving rural communities on how take-home policy changes were received and implemented and how these changes impacted their addiction treatment and recovery. Methods We completed semi-structured individual qualitative interviews in 2 phases: (1) August–October 2020 and (2) November 2020–January 2021 (total n = 46), anticipating possible policy changes as the pandemic progressed. We interviewed patients with OUD enrolled at 3 rural OTPs in Oregon. Participants received varying take-home methadone allowances following the COVID-19-related policy changes. All interviews were conducted via phone, audio-recorded, and transcribed. We conducted a thematic analysis, iteratively coding transcripts, and deductively and inductively generating codes. Results The 46 participants included 50% women and 89% had Medicaid insurance. Three main themes emerged in the analysis, with no differences between study phases: (1) Adapting to changing OTP policies throughout the pandemic; (2) Recognizing the benefits, and occasional struggles, with increased take-home methadone dosing; and (3) Continuing policies and procedures post-pandemic. Participants described fears and anxieties around ongoing methadone access and safety concerns prior to OTP policy changes, but quickly adapted as protocols soon seemed “natural.” The majority of participants acknowledged significant benefits to increased take-homes independent of reducing COVID-19 infection risk including feeling “more like a normal person,” improved recovery support, reduced time traveling, and having more time with family and for work. Looking to a post-pandemic future, participants thought some COVID-19-related safety protocols should continue that would reduce risk of other infections, make OTP settings less stressful, and result in more individualized care. Conclusions As the pandemic progressed, study participants adapted to rapidly changing OTP policies. Participants noted many unanticipated benefits to increased take-home methadone and other COVID-19 protocols including strengthened self-efficacy and recovery and reduced interpersonal conflict, with limited evidence of diversion. Patient perspectives should inform future policies to better address the ongoing overdose epidemic.