Buprenorphine exposures in adolescents and adults: A 10‐year experience of a French Poison Control Center

Abstract

In terms of pharmacology, the opioid buprenorphine is complex and exclusive because it is a partial muopioid agonist and kappa-opioid antagonist with high receptor affinity. Buprenorphine has the same effectiveness as methadone to treat opioid use disorders [1]. Both drugs contribute to significant reductions in allcause and opioid-associated mortality. Buprenorphine shows lower toxicity regarding its pharmacodynamic properties and presents less severe opioid syndromes with a “ceiling effect” for respiratory depression [2]. This means that if a certain dose is reached, the ingestion of more buprenorphine does not cause further suppression of the respiratory drive conversely to methadone, which therefore requires careful management and supervision [3]. Moreover, buprenorphine can be misused, that is, injected or snorted, which may lead to adverse outcomes or diversion to the illicit market [4]. Boulamery et al. contributed an original article entitled “Buprenorphine exposures in adolescents and adults: A 10-year experience of a French Poison Control Center” [5]. This team has already longstanding expertise on this topic and previously studied methadone and buprenorphine exposures in children [1]. Although the level of opioid overdose in France has not reached the alarming level it has in the United States, physicians are concerned, especially since opioid prescriptions are one of the main causes of misuse overdose worldwide. First, the authors extracted 199 medical reports from patients, exposed to buprenorphine, who had called the Poison Center, excluding patients aged 10 and under. Second, the authors focused on patients with severe picture, according to the Poison Severity Score [6]. Exposures to suicide attempts were observed in almost half of patients, who co-ingested buprenorphine with benzodiazepines or antidepressants, indicating that those patients had to be referred to a health care facility for observation. Nonetheless, the number of severity cases was low. Severe pictures (Poison Severity Score = 3) occurred in 4.5% of patients, all of them recovered and no death was observed. These interesting results call for several comments. Authors found that suicide attempts accounted for 48% of exposures, which is surprising because high-dose opioid self-administration as a method of attempted suicide is quite uncommon [7]. Such observation may be explained by the high prevalence of psychiatric comorbidity in this population (considering the main associated co-ingestants), but can also be limited by the retrospective study which may have led to coding errors, potentially resulting in changes in the causes of the reported buprenorphine exposures. Benzodiazepines were the most common drugs taken with buprenorphine. This observation is of paramount importance since 30% of patients with opioid use disorder who receive opioid maintenance treatment also receive benzodiazepine prescriptions. This co-ingestion increases the risk of overdose in these patients due to the cumulative central nervous system depression. Many reasons may explain why patients suffering from opioid use disorder take benzodiazepines, either prescribed by physicians or diverted. For example, benzodiazepines may be taken to relieve symptoms of certain anxiety disorders, and to manage sleep, but also to avoid getting high and to fight against craving [8]. Management of overdose with opioids, including buprenorphine, is based on naloxone administration, although naloxone may be less effective due to its short half-life (30 to 80 min) compared to that of buprenorphine (2 to 4 h), but also because of the long acting of norbuprenorphine, its active metabolite. Moreover, regarding the frequent association of drugs co-ingested with buprenorphine overdose, clinical pictures may lack specificity. What is remarkable in this study [5] is the high number of patients exposed to buprenorphine (66%) who were referred to emergency departments. Such departments are usually overcrowded, but hospitalization and/or observation ensure continuity of care after the detoxification phase. The medical and psychosocial care of these patients, the assessment of substance use disorders, the evaluation of associated somatic or psychiatric comorbidity, and the performance of brief intervention are part of the missions of the liaison team [9]. Received: 16 June 2021 Accepted: 28 June 2021