“It’s within your own power”: shared decision-making to support transitions to buprenorphine

Suen L.W., Chiang A.Y., Jones B.L., Soran C.S., Geier M., Snyder H.R., Neuhaus J., Myers J.J., Knight K.R., Bazazi A.R., Coffin P.O.

ImportanceThe rise of high-potency opioids such as fentanyl makes buprenorphine initiation challenging due to the risks of precipitated withdrawal, prompting the exploration of strategies, such as low-dose initiation (LDI) of buprenorphine. However, no comparative studies on LDI outcomes exist.ObjectiveTo evaluate outpatient outcomes associated with 2 LDI protocols of buprenorphine among individuals with opioid use disorder (OUD) using fentanyl.Design, Setting, and ParticipantsThis cohort study analyzed data on adults with OUD who self-reported daily fentanyl use and underwent buprenorphine initiation using LDI. Data were extracted from the electronic health records of 2 substance use disorder treatment clinics using a specialty behavioral health pharmacy in San Francisco, California, from May 2021 to November 2022.ExposuresType of LDI protocol selected by individuals: 4-day or 7-day protocol.Main Outcomes and MeasuresThe primary outcome was successful buprenorphine initiation, defined as self-reported LDI completion and pickup of a refill maintenance prescription, and buprenorphine retention. Logistic regression with generalized estimating equations assessed associations between LDI protocol (4-day vs 7-day) and successful initiation, adjusting for multiple attempts, age, gender identity, race and ethnicity, and housing status. Kaplan-Meier survival curves were used to estimate buprenorphine retention, and survival curves were adjusted using a fitted Cox proportional hazards regression model.ResultsA total of 126 individuals (median [IQR] age, 35 [29-44] years; 90 identified as men [71%]; 26 [21%] identified as Black or African American, 20 [16%] as Latine, and 66 [52%] as White individuals) with 175 initiation attempts were included. Across attempts, 72 (41%) had a 4-day LDI protocol and 103 (59%) had a 7-day protocol. Initiation was successful in 60 attempts (34%), including 27 (38%) among 4-day protocol and 29 (28%) among 7-day protocol attempts. Buprenorphine retention rate at 28 days was 21% for a 4-day protocol and 18% for a 7-day protocol. Logistic regression found no significant differences between LDI protocols and successful initiation, while repeated LDI attempts had lower odds of success (second attempt: adjusted odds ratio [AOR], 0.30 [95% CI, 0.14-0.66]; third or more attempt: AOR, 0.22 [95% CI, 0.09-0.53]). Unadjusted and adjusted survival models did not detect a significant difference in retention between LDI protocol types.Conclusions and RelevanceThis cohort study found that among people with OUD using fentanyl and attempting outpatient LDI of buprenorphine, successful buprenorphine initiation and retention rates were low. Future studies should examine interventions to improve LDI success and increase buprenorphine uptake and retention.

Gregory C., Yadav K., Linders J., Sikora L., Eagles D.

AbstractBackground and AimsBuprenorphine is an evidence‐based treatment for opioid use disorder, and the risk of precipitated withdrawal contributes to its underuse. The goal of this systematic review was to determine the incidence of buprenorphine‐precipitated withdrawal in adults with opioid use disorder.MethodsThis systematic review was registered on PROSPERO (CRD42023437634). We searched Medline, Embase Classic + Embase, and Cochrane CENTRAL from inception to 10 November 2023, and included original research that reported the incidence of sublingual buprenorphine‐precipitated withdrawal in adults with opioid use disorder. Primary screening was completed by four independent reviewers. Full text review, data extraction and risk of bias assessments using the Newcastle Ottawa Scale and the Cochrane Risk of Bias 2 tool were completed by two independent reviewers. The primary outcome was precipitated withdrawal. Secondary outcomes were baseline opioids used, induction dose, initial Clinical Opiate Withdrawal Scale (COWS) score, location of induction, definition and severity of precipitated withdrawal and adverse events. The range of incidence of precipitated withdrawal across studies was described.ResultsOur search yielded 10 197 unique citations. Twenty‐one cohort and five randomized trials met inclusion criteria (n = 4497, range 20–1293). The overall incidence of precipitated withdrawal ranged from 0 to 13.2%. Nine studies defined precipitated withdrawal; definitions were inconsistent. Most patients used heroin at baseline. The most common initial dose of buprenorphine was between 2 mg and 8 mg (range: 0.075 mg–24 mg). Initial minimum COWS score ranged from 5 to 13. Induction locations included home, inpatient, emergency department, pre‐hospital, outpatient and residential units. Of the fifteen studies with cases of precipitated withdrawal, nine studies did not report the severity of withdrawal experienced. Other induction‐related adverse events varied. The overall quality of included studies was poor.ConclusionsThe best available evidence suggests the incidence of buprenorphine‐precipitated withdrawal in adults with opioid use disorder is low and should not be a barrier to use.

Dunn K.E., Strain E.C.

Summary The opioid crisis is an international public health concern. Treatments for opioid use disorder centre largely on the management of opioid withdrawal, an aversive collection of signs and symptoms that contribute to opioid use disorder. Whereas in the past 50 years more than 90 medications have been developed for depression, only five medications have been developed for opioid use disorder during this period. We posit that underinvestment has occurred in part due to an underdeveloped understanding of opioid withdrawal syndrome. This Personal View summarises substantial gaps in our understanding of opioid withdrawal that are likely to continue to limit major advancements in its treatment. There is no firm consensus in the field as to how withdrawal should be precisely defined; 10–550 symptoms of withdrawal can be measured on 18 scales. The imprecise understanding of withdrawal is likely to result in overestimating or underestimating the severity of an individual's withdrawal syndrome or potential therapeutic effects of different candidate medications. The severity of the opioid crisis is not remitting, and an international research agenda for the study and assessment of opioid withdrawal is necessary to support transformational changes in withdrawal management and treatment of opioid use disorder. Nine actionable targets are delineated here: develop a consensus definition of opioid withdrawal; understand withdrawal symptomatology after exposure to different opioids (particularly fentanyl); understand precipitated opioid withdrawal; understand how co-exposure of other drugs (eg, xylazine and stimulants) influences withdrawal expression; examine individual variation in withdrawal phenotypes; precisely characterise the protracted withdrawal syndrome; identify biomarkers of opioid withdrawal severity; identify predictors of opioid withdrawal severity; and understand which symptoms are most closely associated with treatment attrition or relapse. The US Food and Drug Administration recently established a formal indication for opioid withdrawal that has invigorated interest in drug development for opioid withdrawal management. Action is now needed to support these interests and help industry identify new classes of medications so that real change can be achieved for people with opioid use disorder.

Wong S., Fabiano N., Webber D., Kleinman R.A.

Objective The aim of the study is to review and synthesize the literature on high-dose buprenorphine initiation (>12-mg total dose on day of initiation). Methods A scoping review of literature about high-dose buprenorphine initiation was conducted. MEDLINE, Embase, PsycINFO, and Cochrane Central were searched. Randomized controlled trials, prospective and retrospective cohort studies, and case studies/reports published in English before February 13, 2023, were included. Results Fifteen studies reporting outcomes from 580 high-dose buprenorphine initiations were included. Eight studies were in inpatient settings, 3 in emergency departments, 3 in outpatient settings, and 1 in a first-responder setting. Four studies reported high-dose initiations among individuals exposed to fentanyl. There were no reported events of fatal or nonfatal overdose or respiratory depression, although adverse event reporting was inconsistent in published reports. The most reported side effects with high-dose buprenorphine initiation were nausea or vomiting (n = 17) and precipitated withdrawal (n = 7). The most serious reported adverse event was hypotension requiring oral hydration (n = 2). Most studies reported improvements in subjective or objective withdrawal symptoms. The duration of follow-up ranged from none to 8 months. Conclusions High-dose buprenorphine initiation has not been associated with reported cases of overdose or respiratory depression. However, the current literature about high-dose buprenorphine is limited by inconsistent side effect reporting, limited power to detect rare safety events such as respiratory depression, limited follow-up data, and few comparison studies between high-dose and regular initiation protocols. Further prospective data are needed to evaluate the safety and effectiveness of this initiation strategy.

Jones B.L., Geier M., Neuhaus J., Coffin P.O., Snyder H.R., Soran C.S., Knight K.R., Suen L.W.

Abstract Background Buprenorphine is an effective treatment for opioid use disorder (OUD); however, buprenorphine initiation can be complicated by withdrawal symptoms including precipitated withdrawal. There has been increasing interest in using low dose initiation (LDI) strategies to reduce this withdrawal risk. As there are limited data on withdrawal symptoms during LDI, we characterize withdrawal symptoms in people with daily fentanyl use who underwent initiation using these strategies as outpatients. Methods We conducted a retrospective chart review of patients with OUD using daily fentanyl who were prescribed 7-day or 4-day LDI at 2 substance use disorder treatment clinics in San Francisco. Two addiction medicine experts assessed extracted chart documentation for withdrawal severity and precipitated withdrawal, defined as acute worsening of withdrawal symptoms immediately after taking buprenorphine. A third expert adjudicated disagreements. Data were analyzed using descriptive statistics. Results There were 175 initiations in 126 patients. The mean age was 37 (SD 10 years). 71% were men, 26% women, and 2% non-binary. 21% identified as Black, 16% Latine, and 52% white. 60% were unstably housed and 75% had Medicaid insurance. Substance co-use included 74% who used amphetamines, 29% cocaine, 22% benzodiazepines, and 19% alcohol. Follow up was available for 118 (67%) initiations. There was deviation from protocol instructions in 22% of these initiations with follow up. 31% had any withdrawal, including 21% with mild symptoms, 8% moderate and 2% severe. Precipitated withdrawal occurred in 10 cases, or 8% of initiations with follow up. Of these, 7 had deviation from protocol instructions; thus, there were 3 cases with follow up (3%) in which precipitated withdrawal occurred without protocol deviation. Conclusions Withdrawal was relatively common in our cohort but was mostly mild, and precipitated withdrawal was rare. Deviation from instructions, structural barriers, and varying fentanyl use characteristics may contribute to withdrawal. Clinicians should counsel patients who use fentanyl that mild withdrawal symptoms are likely during LDI, and there is still a low risk for precipitated withdrawal. Future studies should compare withdrawal across initiation types, seek ways to support patients in initiating buprenorphine, and qualitatively elicit patients’ withdrawal experiences.

Durand M., Selby K., Okan Y.

Consistent with the principles of evidence-based medicine, effectively communicating evidence (including risks) in medicine is an essential part of shared decision making (SDM). SDM has been defined as ‘an approach where clinicians and patients share the best available evidence when faced with the task of making decisions, and where patients are supported to consider options, to achieve informed preferences’.1 This process relies on access and understanding of evidence-based information by both patients and healthcare professionals. This includes outcome probabilities, typically presented numerically. Yet, a considerable fraction of the population is confronted with limited numeracy. Numeracy is defined as the ability to understand, use and interpret numbers and calculations in everyday situations.2 This difficulty processing numbers is a significant barrier to effective communication in healthcare and SDM. Many studies demonstrate the potential of visuals to facilitate the presentation and understanding of both qualitative and quantitative information, including numbers.3 4 We define visuals broadly, as including pictures and graphical displays used to show or explain something. We define graphical displays as two-dimensional graphical representations showing a risk information, and graph literacy, as the ability to understand information presented graphically. Our systematic review and meta-analysis of 54 randomised controlled trials comparing visuals and text to text alone (42 in the meta-analysis) suggested that visuals moderately improved knowledge/understanding and information recall, but largely increased knowledge/understanding for people with limited health literacy (n=13).5 Health literacy is defined as the capacity to obtain, process and understand basic health information and services needed to make appropriate health decisions. Our narrative synthesis suggested that visuals with few words may be most helpful in conveying health information. These findings further support the hypothesis of pictorial superiority. Pictorial superiority is defined as the tendency to remember concrete items more easily when presented as pictures rather than …

Clayman M.L., Scheibler F., Rüffer J.U., Wehkamp K., Geiger F.

Shared decision-making (SDM) has gained acceptance as a preferred and ideal method for medical decision-making.1 2 As SDM concepts and assessments initially focused on the clinical encounter, efforts to improve decision-making for patients initially did so, as well.3 This resulted in a plethora of patient-focused interventions (eg, patient decision aids)4 while lacking concurrent development of a systems-oriented approach to change the structural and procedural requirements of medicine for optimal implementation of SDM practice.5 ### Rationale and context for developing The Six Steps of SDM We developed The Six Steps of SDM to fill gaps in coordination among theory, measurement, interventions and implementation of SDM. That is, ideally, theory should drive both measurement and development of interventions (including skills training and tools such as decision aids), and therefore, influence implementation. However, SDM theories, assessments, decision tools and curricula were not developed as part of a comprehensive, implementation-oriented strategy. Any comprehensive model, therefore, should conceptually harmonise theory-driven measures that fulfil various purposes. For example, the measures that would be best used to help assess effectiveness of clinical training and provide feedback to improve their skills may well be different from assessments used to determine how patients perceive their providers’ abilities with respect to SDM. Nonetheless, the set of assessments should work together conceptually. Examples of this lack of harmonisation can be seen, for example, in how provider training for SDM has developed. Typically, SDM theories and assessments were not developed with teaching in mind. Therefore, existing models of instruction may not align with validated measures of SDM, making it difficult to tell if the instruction was successful.6 Measures of SDM, in turn, have mostly been developed to describe and define decision-making in clinical encounters, not as pedagogical tools. As a corollary, many models used to teach and evaluate communication skills (eg, The Four Habits),7 while they may …

Weimer M.B., Herring A.A., Kawasaki S.S., Meyer M., Kleykamp B.A., Ramsey K.S.

Abstract Treatment of opioid use disorder (OUD) with buprenorphine has evolved considerably in the last decade as the scale of the OUD epidemic has increased along with the emergence of high-potency synthetic opioids (HPSOs) and stimulants in the drug supply. These changes have outpaced the development of prospective research, so a clinical consideration document based on expert consensus is needed to address pressing clinical questions. This clinical considerations document is based on a narrative literature review and expert consensus and will specifically address considerations for changes to the clinical practice of treatment of OUD with buprenorphine for individuals using HPSO. An expert panel developed 6 key questions addressing buprenorphine initiation, stabilization, and long-term treatment for individuals with OUD exposed to HPSO in various treatment settings. Broadly, the clinical considerations suggest that individualized strategies for buprenorphine initiation may be needed. The experience of opioid withdrawal negatively impacts the success of buprenorphine treatment, and attention to its management before and during buprenorphine initiation should be proactively addressed. Buprenorphine dose and dosing frequency should be individualized based on patients’ treatment needs, the possibility of novel components in the drug supply should be considered during OUD treatment, and all forms of opioid agonist treatment should be offered and considered for patients. Together, these clinical considerations attempt to be responsive to the challenges and opportunities experienced by frontline clinicians using buprenorphine for the treatment of OUD in patients using HPSOs and highlight areas where prospective research is urgently needed.

Grande L.A., Cundiff D., Greenwald M.K., Murray M., Wright T.E., Martin S.A.

Dunn K.E., Bird H.E., Bergeria C.L., Ware O.D., Strain E.C., Huhn A.S.

BackgroundOpioid withdrawal can be expressed as both a spontaneous and precipitated syndrome. Although spontaneous withdrawal is well-characterized, there is no operational definition of precipitated opioid withdrawal.MethodsPeople (N = 106) with opioid use disorder maintained on morphine received 0.4 mg intramuscular naloxone and completed self-report (Subjective Opiate Withdrawal Scale, SOWS), visual analog scale (VAS), Bad Effects and Sick, and observer ratings (Clinical Opiate Withdrawal Scale, COWS). Time to peak severity and minimal clinically important difference (MCID) in withdrawal severity were calculated. Principal component analysis (PCA) during peak severity were conducted and analyzed with repeated measures analyses of variance (ANOVA).ResultsWithin 60 min, 89% of people reported peak SOWS ratings and 90% of people had peak COWS scores as made by raters. Self-reported signs of eyes tearing, yawning, nose running, perspiring, hot flashes, and observed changes in pupil diameter and rhinorrhea/lacrimation were uniquely associated with precipitated withdrawal. VAS ratings of Bad Effect and Sick served as statistically significant severity categories (0, 1–40, 41–80, and 81–100) for MCID evaluations and revealed participants' identification with an increase of 10 [SOWS; 15% maximum percent effect (MPE)] and 6 (COWS; 12% MPE) points as meaningful shifts in withdrawal severity indicative of precipitated withdrawal.ConclusionData suggested that a change of 10 (15% MPE) and 6 (12% MPE) points on the SOWS and COWS, respectively, that occurred within 60 min of antagonist administration was identified by participants as a clinically meaningful increase in symptom severity. These data provide a method to begin examining precipitated opioid withdrawal.

Montori V.M., Ruissen M.M., Hargraves I.G., Brito J.P., Kunneman M.

Care happens in interaction between the patient and the clinician, in conversation where the patient and clinician uncover or develop a shared understanding of the problematic situation of the patient and identify, discover, or invent ways to make that situation better, given what each patient prioritises and seeks.1 Thus, to get the right care for each patient, patient and clinician collaborate and deliberate together to figure out what to do.2 Shared decision-making (SDM) has been traditionally defined as a collaborative approach by which, in partnership with their clinician, patients are encouraged to think about the available care options and the likely benefits and harms of each, to communicate their preferences, and help select the best course of action that fits these.3 This definition is limited to situations in which the problem and the pertinent options to address it can be defined a priori, and the main task is to find the option that best matches the patient’s preferences. Thought in this way, SDM may involve distributing decision aids for patients to come prepared for the consultation and using tools to elicit and document patient preferences. This practice has been proposed as an expression of patient-centred care, a way of involving patients, an antidote to medical paternalism, and as a way to promote high-value care.3 But anytime, a patient and clinician figure out together what to do about the patient’s situation, they are doing SDM. Although there are multiple models and accounts of what SDM is and is not,2 4 5 in practice, SDM starts by determining the nature of the problematic situation the patient is experiencing. This often requires considering insights that only the patient and perhaps their family can share, insights about both the patient’s biology and biography. Then clinicians must mobilise their competence …

Randall A., Hull I., Martin S.A.

Buprenorphine-naloxone (BUP-NX) is a lifesaving treatment for opioid use disorder. The increasing use of illicitly manufactured fentanyl, however, has made initiating BUP-NX more likely to precipitate withdrawal-an experience that deters treatment and causes return to use. If BUP-NX cannot be successfully started, it cannot work. We describe the case of a patient who was able to transition to a therapeutic dose of BUP-NX less than 3 hours after his last illicitly manufactured fentanyl use by choosing to self-administer intranasal naloxone. After the naloxone, the transition took 31 minutes, including 14 minutes of expected moderately severe withdrawal. He remains in care with BUP-NX and would recommend this transition approach to others.

Schoenfeld E.M., Westafer L.M., Beck S.A., Potee B.G., Vysetty S., Simon C., Tozloski J.M., Girardin A.L., Soares W.E.

Objectives Medications for opioid use disorder (MOUD) prescribed in the emergency department (ED) have the potential to save lives and help people start and maintain recovery. We sought to explore patient perspectives regarding the initiation of buprenorphine and methadone in the ED with the goal of improving interactions and fostering shared decision making (SDM) around these important treatment options. Methods We conducted semistructured interviews with a purposeful sample of people with opioid use disorder (OUD) regarding ED visits and their experiences with MOUD. The interview guide was based on the Ottawa Decision Support Framework, a framework for examining decisional needs and tailoring decisional support, and the research team's experience with MOUD and SDM. Interviews were recorded, transcribed, and analyzed in an iterative process using both the Ottawa Framework and a social–ecological framework. Themes were identified and organized and implications for clinical care were noted and discussed. Results Twenty-six participants were interviewed, seven in person in the ED and 19 via video conferencing software. The majority had tried both buprenorphine and methadone, and almost all had been in an ED for an issue related to opioid use. Participants reported social, pharmacological, and emotional factors that played into their decision making. Regarding buprenorphine, they noted advantages such as its efficacy and logistical ease and disadvantages such as the need to wait to start it (risk of precipitated withdrawal) and that one could not use other opioids while taking it. Additionally, participants felt that: (1) both buprenorphine and methadone should be offered; (2) because “one person's pro is another person's con,” clinicians will need to understand the facets of the options; (3) clinicians will need to have these conversations without appearing judgmental; and (4) many patients may not be “ready” for MOUD, but it should still be offered. Conclusions Although participants were supportive of offering buprenorphine in the ED, many felt that methadone should also be offered. They felt that treatment should be tailored to an individual's needs and circumstances and clarified what factors might be important considerations for people with OUD.

Marshall T., Hancock M., Kinnard E.N., Olson K., Abba-Aji A., Rittenbach K., Stea J.N., Tanguay R., Vohra S.

Shared decision-making (SDM) is an approach to clinical decision-making that includes patients' values and preferences during health-related decisions. Previous research suggests that SDM may be beneficial in the treatment of substance use disorders; however, the impact of SDM in the treatment of opioid use disorder (OUD) remains unclear.To identify relevant peer-reviewed literature related to SDM in the treatment of adults with OUD, and to summarize the main findings according to patient outcomes.The research team conducted a scoping review. The team searched five electronic health databases from database inception until September 2019 using MeSH and keywords related to SDM. The team included only peer-reviewed studies where adults (≥18 years) with OUD were provided a choice and/or allowed input into their treatment plan. Two independent reviewers screened, extracted, and assessed the quality of included studies.Fourteen studies (n = 1748 participants) met inclusion criteria, including seven randomized controlled trials, three non-randomized controlled trials, two observational studies, and one qualitative study. Treatment options included: patient regulated methadone dosing vs. fixed dosing (n = 4 studies), optional vs. mandatory counseling (n = 4 studies), home vs. office buprenorphine inductions (n = 2 studies), and inpatient vs. outpatient treatment (n = 1 study). None of the studies measured SDM with a validated instrument. Seven of 14 studies reported at least one improved patient outcome.The review found few studies that explored whether providing treatment options and/or encouraging participation in decision-making are beneficial for adults with OUD. Preliminary evidence suggests that SDM may be promising for this population. However, the field needs more research on person-centered care and SDM.

Suen L.W., Lee T.G., Silva M., Walton P., Coffin P.O., Geier M., Soran C.S.

Fear and risk of precipitated withdrawal are barriers for initiating buprenorphine in individuals with opioid use disorder, particularly among those using fentanyl. A buprenorphine rapid overlap initiation (ROI) protocol (also knownas "rapidmicro-dosing") utilizing small, escalating doses of buprenorphine can overcome this barrier, reaching therapeutic doses in 3 to 4 days. We sought to demonstrate the feasibility of implementing a buprenorphine ROI protocol for buprenorphine initiation in the outpatient setting.We conducted a retrospective chart review of patients prescribed an outpatient ROI protocol at the Office-based Buprenorphine Induction Clinic from October to December 2020. The ROI protocol utilizes divided doses of sublingual buprenorphine tablets and blister packaging for easier dosing. Patients were not required to stop other opioid use and were advised to follow up on day 4 of initiation.Twelve patients were included, of whom eleven (92%) were using fentanyl at intake. Eleven patients picked up their prescription. Seven patients returned for follow-up (58%), and all 7 completed the ROI protocol. One patient reported any withdrawal symptoms, which were mild. At 30 days, 7 patients (58%) were retained in care, and 5 (42%) were still receiving buprenorphine treatment, 4 (33%) of whom had been abstinent from nonprescribed opioid use for ≥2 weeks.The ROI protocol was successful in initiating buprenorphine treatment for patients in our outpatient clinic, many of whom were using fentanyl. The ROI protocol may offer a safe alternative to traditional buprenorphine initiation and warrants further study.