Objective: To evaluate literature reporting on the role of norepinephrine in alcohol withdrawal and to determine the safety and efficacy of α ₂ -agonists in reducing symptoms of this severe condition. Data Sources: Articles evaluating the efficacy and safety of the α ₂ -agonists clonidine and dexmedetomidine were identified from an English-language MEDLINE search (1966-December 2010). Key words included alcohol withdrawal, delirium tremens, clonidine, dexmedetomidine, α ₂ -agonist, norepinephrine, and sympathetic overdrive. Study Selection and Data Extraction: Studies that focused on the safety and efficacy of clonidine and dexmedetomidine in both animals and humans were selected. Data Synthesis: The noradrenergic system, specifically sympathetic overdrive during alcohol withdrawal, may play an important role in withdrawal symptom development. Symptoms of sympathetic overdrive include anxiety, agitation, elevated blood pressure, tachycardia, and tremor. Therefore, α ₂ -agonists, which decrease norepinephine release, may have a role in reducing alcohol withdrawal symptoms. The majority of controlled animal and human studies evaluated clonidine, but the most recent literature is from case reports on dexmedetomidine. The literature reviewed here demonstrate that these 2 α ₂ -agonists safely and effectively reduce symptoms of sympathetic overdrive and concomitant medication use. Dexmedetomidine may offer an advantage over current sedative medications used in the intensive care unit, such as not requiring intubation with its use, and therefore further study is needed to fully elicit its benefit in alcohol withdrawal. Conclusion: Clonidine and dexmedetomidine may provide additional benefit in managing alcohol withdrawal by offering a different mechanism of action for targeting withdrawal symptoms. Based on literature reviewed here, the primary role for clonidine and dexmedetomidine is as adjunctive treatment to benzodiazepines, the standard of care in alcohol withdrawal.

Brian McCarthy, Hannah Bunn, Morgan Santalucia, Charlotte Wilmouth, Andrew Muzyk, Colin M. Smith. Clin Psychopharmacol Neurosci 2023;21:609-16. https://doi.org/10.9758/cpn.23.1081

Background: Pharmacists are on the frontline caring for patients at risk of an opioid overdose and for patients with an opioid use disorder (OUD). Dispensing naloxone and medications for OUD and counseling patients about these medications are ways pharmacists can provide care. Key to pharmacists’ involvement is their willingness to take on these practice responsibilities. Methods: The purpose of this scoping review is to identify, evaluate, and summarize published literature describing pharmacists’ attitudes toward naloxone and medications for OUD, i.e., methadone, buprenorphine, and naltrexone. All searches were performed on December 7, 2018, in 5 databases: Embase.com , PubMed.gov , Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCOhost, Cochrane Central Register of Controlled Trials via Wiley, and Clarivate Web of Science. Articles included original research conducted in the United States, described attitude-related language toward naloxone and medications for OUD, and pharmacists. Results: A total of 1323 articles were retrieved, 7 were included. Five studies reported on pharmacists’ attitudes toward naloxone dispensing, 1 study reported on attitudes toward naloxone, buprenorphine, and buprenorphine/naloxone, and 1 reported on attitudes toward buprenorphine/naloxone. Respondents were diverse, including pharmacists from different practice specialties. Studies found that pharmacists agreed with a naloxone standing order, believed that naloxone should be dispensed to individuals at risk of an opioid overdose, and were supportive of dispensing buprenorphine. A minority of pharmacists expressed negative attitudes. Barriers cited to implementation included education and training, workflow, and management support. Conclusions: Pharmacists were positive in their attitudes toward increased practice responsibilities for patients at risk of an opioid overdose or with an OUD. Pharmacists must receive education and training to be current in their understanding of OUD medications, and they must be supported in order to provide effective care to this patient population.

Introduction: Substance use disorders, including opioid use disorders, are a major public health concern in the United States. Between 2005 and 2014, the rate of opioid-related emergency department (ED) visits nearly doubled, from 89.1 per 100,000 persons in 2005 to 177.7 per 100,000 persons in 2014. Thus, the ED presents a distinctive opportunity for harm-reduction strategies such as distribution of naloxone to patients who are at risk for an opioid overdose. Methods: We conducted a systematic review of all existing literature related to naloxone distribution from the ED. We included only those articles published in peer-reviewed journals that described results relating to naloxone distribution from the ED. Results: Of the 2,286 articles we identified from the search, five met the inclusion criteria and had direct relevance to naloxone distribution from the ED setting. Across the studies, we found variation in the methods of implementation and evaluation of take-home naloxone programs in the ED. In the three studies that attempted patient follow-up, success was low, limiting the evidence for the programs’ effectiveness. Overall, in the included studies there is evidence that distributing take-home naloxone from the ED has the potential for harm reduction; however, the uptake of the practice remained low. Barriers to implementation included time allocated for training hospital staff and the burden on workflow. Conclusion: This systematic review of the best evidence available supports the ED as a potential setting for naloxone distribution for overdose reversal in the community. The variability of the implementation methods across the studies highlights the need for future research to determine the most effective practices.