Commentary on D'Agata Mount et al.: Higher dose buprenorphine to improve retention in opioid use disorder treatment, prevent relapse, and optimize integrated care interventions

D'Agata Mount et al. [1] offer convincing proofs of the superiority of 32 mg/day buprenorphine for the low-threshold treatment of opioid use disorder (OUD), despite a non-randomized uncontrolled design. The study is a retrospective longitudinal observation and provides within group and between group comparisons with the 24 mg/day dose, identifying strong differences in a relatively small sample. This is undoubtedly fitting, the benchmark is now 32 mg, it was 24 mg before [2] and 16 mg before that [3]. Consistently, every round of evaluations has shown the use of higher doses to be associated with better outcomes and to be one of the best overdose prevention tools [4].

One detail of the results stimulates reflection, which is concerning the increased influence of non-physiologic triggers of drug use when the buprenorphine dose is raised to 32 mg. Nothing in the results indicates it is a warning for the higher dose approach. In any case, using a wider range of buprenorphine doses may enhance the possibility to examine quantity and duration of treatment in relation to specific interventions, and further improve outcomes. To avoid a simplistic medication-centered approach, we could envision stepwise multi-phase protocols to address individual problems within a precision medicine framework that includes patients' genetic profile, lifestyle and environment, along with characteristics of disease and the proposed treatment [5]. By now, we can identify triggers and match them with effective interventions. For example, the effects of psychosocial stressors can be partly reduced by adequate buprenorphine dosing [6], but the administration of buprenorphine has limited efficacy on triggers of relapse tied to environmental stressors and social determinants of health, which require the development of sustainable long-term preventive community based interventions [7]. National initiatives such as the National Institute of Health ‘Helping to End Addiction Long-term Initiative (HEAL)’ will provide a path to make evidence-based preventive services accessible to all persons who experience risk for substance use disorder and relapse [8].

When it comes to the evaluation of triggers of drug use, a single measure of craving would be more powerful than the dichotomous values for each of the triggers in the study. Craving is an important patient-reported symptom, but finding consensus on evaluation methods remains a work in-progress [9]. In this study, craving is listed as one of the physiologic withdrawal symptoms, instead of being considered a final expression of a diverse range of triggers [10]. Following the latter interpretation, all physiologic and non-physiologic factors described in the study would be expressed through ratings of craving and drug seeking. How this can be done while preserving the individuality and traceability of each trigger requires a structured form of craving evaluation, the proof that it is a more informative tool than visual analog scales, and the agreement that craving measures are not limited to acute withdrawal [9].

One last reflection is about the choice of the ‘best fit’ setting to test a higher dose buprenorphine approach. In the study, mental health stressors are among triggers of relapse in OUD patients treated for medical conditions, namely hepatitis C virus, and the existence of comorbidities in this group of patients is discussed as a potential limit to the generalizability of the results. On the other hand, this limit can be a strength, and treatment of special populations can become a strong support to wider implementation. Following the lost opportunity with HIV care, where high retention rates in retroviral treatment have not translated into overdose prevention [11], we have learned that it can be hard, but not impossible to reach out to people who use drugs. Providing and receiving treatment for a comorbid condition represents one possibility to connect and deliver drug interventions within a harm reduction paradigm. In particular, the integrated treatment of comorbid OUD patients has a natural, underutilized and potentially consequential place in primary care (PC), where retention in treatment is favorable [12]. It is the responsibility of clinical and community research to provide potential PC prescribers with the information that 32 mg, and perhaps higher dose buprenorphine is safe, effective and may facilitate treatment acceptability and ease management [13]. PC providers in turn may find a stronger motivation to prescribe medications for OUD and to educate patients and families. In fact, although a minority of PC providers feel comfortable handling buprenorphine [14], as many as 61% Americans do not even know that PC physicians can prescribe buprenorphine, although 82% of potential patients would feel comfortable to receive the treatment by their family doctor [15].

Paolo Mannelli: Conceptualization; writing—original draft.

The author declares funds for research, fees for consulting, and educational services from Indivior PLC, Alkermes, Guidepoint global.