Buprenorphine and methadone are the two main opioid agonist treatments approved for opioid use disorder. Buprenorphine is a partial agonist of the mu opioid receptors, which has been merely available through sublingual form until now. In practice, the use of buprenorphine is smoother than that of methadone, and it induces reduced risks of overdose. However, sublingual buprenorphine also exposes to risks (e.g., withdrawal, misuse) and constraints (e.g., daily intake). Three new galenic formulations of prolonged-release buprenorphine (PRB) are being commercialized and should allow some improvements in patients' comfort and safety. This narrative review aims to describe the main technical features and efficacy and safety data of these PRBs, as well as patients' and professionals' expectancies and concerns, using data of the scientific literature and the regulatory texts. PRBs consist of one subcutaneous implant and two subcutaneous injection depots. Sixmo®/Probuphine® is a six-month-long implant which needs to be surgically placed and removed and is approved for subjects previously treated with a maximum daily dose of 8mg of sublingual buprenorphine, and can be used only for two successive periods of six months before the subject needs to be switched back to sublingual form. Sublocade® is a one-month-long depot formulation that is indicated in switch from sublingual buprenorphine, and which proposes only two dose schemes, i.e., 100 and 300mg monthly. Buvidal®/Brixadi® is a one-week- or one-month-long depot formulation with multiple dosages, which can be used in initiation or in switched from sublingual formulations. While opioid users report some concerns with a risk of coercive use of long-acting forms of buprenorphine, both users and professionals deem that these new specialties could be particularly appreciated in stabilized patients bothered with the daily intake of the treatments, or specific situations at risk of treatment dropout (e.g., following hospital discharge or prison release).

[Prolonged-release buprenorphine formulations: Perspectives for clinical practice].

AIMS Although medicine misuse is a public health issue, it has multiple meanings in the medical literature. This study aimed to characterize, classify and identify the most appropriate definitions of medicine misuse. METHODS A systematic review was performed in Medline, ISI Web of Science, SocINDEX, PsycInfo, PsycArticles and Psychological and Behavioral Sciences Collection, using keywords related to "misuse", "appropriateness" and "medicine" between 1 November 2008 and 25 August 2020. Additional searches were conducted in websites of regulatory agencies and public health institutions. Two authors independently selected studies providing both definitions and examples of misuse, while a third resolved disagreements. Definitions were used to propose a hierarchical classification based on initiator, intent, purpose and context of medicine misuse. The study is registered on PROSPERO: CRD42018115789. RESULTS Of 3404 identified records, 51 were included. A total of 71 definitions and 74 examples of misuse were retrieved. When the prescriber is initiator and according to intent, potential medicine misuse referred to "intentional or unintentional prescribing not in line with clinical evidence". Based on context, they could prescribe medicines not clinically justified, i.e. overprescribing, or prescribe indicated medicines incorrectly, i.e. misprescribing. Among other groups of definitions, those overlapping with drug abuse or medication use errors were considered out-of-scope. CONCLUSION This systematic review provides a comprehensive overview of the terms and definitions used to characterize medicine misuse and could serve as a basis for a terminology that makes clear distinctions between misuse, abuse and errors.

Medicine misuse: A systematic review and proposed hierarchical terminology.

Analgesic opioid use disorders in patients with chronic non-cancer pain: A holistic approach for tailored management.

(1) Background: Chronic non-cancer pain (CNCP) remains a public health challenge around the world. Opioids (PO) have been increasingly used in the treatment of CNCP in the last 20 years. This study aimed to assess the prevalence of opioid misuse and prescribed-opioid use disorder (p-OUD) among patients with CNCP in a pain centre in France, and to analyse risk factors for moderate or severe p-OUD. (2) Method: A cross-sectional study was conducted, including patients consulting for pain management in the pain centre of Brest University Hospital. A self-questionnaire was administered (sociodemographic data, medical data, PO misuse, and p-OUD according the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM 5) criteria). Descriptive, univariate, and multivariate analyses were conducted, together with a principal component analysis, in order to identify factors associated with p-OUD. (3) Results: In total, 115 patients were included, the majority of whom were women, with a mean age of 52 years old [18–82]; 64.3% (n = 74) had a current prescription for opioid analgesics (weak or strong). In this group, 56.7% (n = 42) had no or only mild p-OUD and 43.3% (n = 32) had current moderate or severe p-OUD. Patients with moderate or severe p-OUD were more likely to have a current antidepressant prescription, to have had psychotherapy, to currently use strong opioids and oxycodone, and to report taking more frequent doses than prescribed and feeling dependent. (4) Conclusions: We showed that the prevalence of current moderate/severe p-OUD concerned 43.3% of the patients with a CNCP seeking treatment in a pain centre. According to these results, several measures are relevant in managing p-OUD among patients with CNCP.

Analgesic Opioid Misuse and Opioid Use Disorder among Patients with Chronic Non-Cancer Pain and Prescribed Opioids in a Pain Centre in France.

Resumo Justificativa A Comissao para o Manejo da Dor estabeleceu um plano de melhoria no controle da dor em 2012. Objetivo Avaliar as tendencias do consumo de analgesicos em um hospital de ensino terciario e o impacto economico associado. Metodos Estudo descritivo, retrospectivo, feito entre 2011 e 2015. A analise incluiu: produtos anti‐inflamatorios e antirreumaticos nao esteroides, analgesicos opioides e outros analgesicos e antipireticos. Os dados foram convertidos em DDD/100 leitos‐dia para analisar as tendencias de consumo. Principal medida do desfecho: avaliacao do consumo de analgesicos apos o estabelecimento de um plano de melhoria no controle da dor. Resultados O consumo total de produtos anti‐inflamatorios e antirreumaticos nao esteroides diminuiu em 24,8 DDD/100 leitos‐dia (−28,3%), representando a maior parte da reducao total do consumo de analgesicos (−13%) e o custo total (−44,3%). O consumo global de opioides aumentou acentuadamente de 22,3 DDD/100 leitos‐dia em 2011 para 26,5 DDD/100 leitos‐dia em 2015 (+18,9%). Em 2011, o opioide mais consumido foi a morfina (8,6 DDD/100 leitos‐dia). No entanto, houve uma tendencia crescente no consumo de fentanil (de 8,1 para 12,1 DDD/100 leitos‐dia em 2015), o que resultou na substituicao de morfina por fentanil como o opioide mais consumido em 2015 (12,1 DDD/100 leitos‐dia). Em 2015, o grupo dos outros analgesicos e antipireticos representou 46,2% do consumo total de analgesicos. Acetaminofeno foi o analgesico mais consumido (53,2 DDD/100 leitos‐dia em 2015) e teve o maior custo total, representou 55,4% do custo total em 2015. Conclusao O consumo de opioides mostrou uma tendencia crescente durante o periodo de cinco anos, fentanil substituiu morfina como o opioide mais usado. Em geral, o uso diminuido de analgesicos foi devido a tendencia decrescente do consumo de produtos anti‐inflamatorios e antirreumaticos nao esteroides.

Tendências no consumo hospitalar de analgésicos após a implantação de plano de melhoria do controle da dor

Since the 1990s, the use of prescription opioids has largely spread, which has brought a real progress in the treatment of pain. The long-term use of prescription opioid is sometimes required, and may lead to pharmacological tolerance and withdrawal symptoms, i.e. pharmacological dependence on prescription opioids. Occasionally, this may also lead to misuse of prescription opioids (MPO). MPO preferentially occurs in vulnerable individuals, i.e., those with a young age, history of other addictive or psychiatric disorders, especially anxious and depressive disorders. MPO is associated with numerous complications, including an increased risk of fatal overdose. Prevention of MPO begins before the opioid prescription, with the identification of potential vulnerability factors. A planned and personalized monitoring should be systematically implemented. In vulnerable patients, contractualizing the prescription is warranted. During follow-up, the relevance of the prescription should be regularly reconsidered, according to the benefit observed on pain and the potential underlying signs of MPO. Patients with suspected MPO should be referred early to pain or addiction centers. The treatment of MPO should be based on multidisciplinary strategies, involving both the addiction and pain aspects: progressive opioid withdrawal, non-pharmacological measures against pain, or switching to medication-assisted treatment of addiction (i.e., buprenorphine or methadone).

R. Schwan

Papers

Mésusage et dépendance aux opioïdes de prescription : prévention, repérage et prise en charge