If you work in a psychiatric unit, you probably often face the challenge of managing patients with co-occurring substance use disorders (SUDs). Benzodiazepines offer considerable benefits in the management of alcohol withdrawal symptoms and agitation, but they require a mindful approach when you’re working with patients with a history of alcohol use disorder (AUD) or other SUDs. Approximately 12.6% of the US population reported benzodiazepine use within the previous year, with misuse accounting for nearly 20% of all use (Maust DT et al, Psychiatr Serv 2019;70(2):97–106). Risk of misuse is highest for adults 18–25, and concomitant cannabis or alcohol use has been associated with a higher risk of misuse. Given the potential risks of cognitive impairment, falls, dependence, misuse, and even higher mortality rate among patients with AUD, the use of benzodiazepines warrants caution (Heikkinen M et al, Addiction 2021;116(8):1990–1998). This article provides an overview of important considerations when using benzodiazepines for patients with SUDs in psychiatric inpatient settings.

Inpatient use of benzodiazepines

Benzodiazepines rank among the most frequently misused substances, and misuse is prevalent among patients with AUD. Both benzodiazepines and alcohol act via the ­GABAergic system, leading to a potent combined effect that increases the likelihood of adverse outcomes, including, in severe cases, fatal overdoses. Further, exposure to benzodiazepines can trigger a return to use for patients in recovery from AUD. So, before prescribing benzodiazepines, thoroughly check the patient’s history, their substance use patterns, and any factors that might increase risk of a relapse, such as poor physical health, poor sleep, or psychosocial stressors (Sliedrecht W et al, Psychiatry Res 2019;278:97–115).

A good rule of thumb is to keep the duration of benzodiazepine use as short and the dosage as low as possible, considering that tolerance and physical dependence on benzodiazepines can develop in just one week (Vinkers CH et al, Adv Pharmacol Sci 2012;2012:416864). In the days leading up to discharge, taper the dosage gradually since abrupt discontinuation can produce a rebound of anxiety, insomnia, and irritability. Typically, a dose reduction of 25%–50% every week is well tolerated, but you can taper the dose as quickly as every two or three days in many cases. A taper is not necessary if the benzodiazepine use was sporadic during the inpatient admission. 

For the medical management of alcohol withdrawal, I prefer long-acting benzodiazepines, such as chlordiazepoxide (Librium) or diazepam (Valium), over short-acting agents like alprazolam (Xanax). This is because a longer half-life allows for more consistent management of withdrawal symptoms and a smoother, more tolerable experience for the patient. The pharmacokinetic profiles of chlordiazepoxide and diazepam are similar; however, both have been subject to recent drug shortages, so the choice between them will largely be guided by hospital formulary and availability. Typical symptom-triggered doses of chlordiazepoxide are 25–100 mg PO, and the range for diazepam is 5–10 mg PO, as needed every four to six hours based on severity of withdrawal symptoms. Lorazepam (Ativan), while not a long-acting benzodiazepine, is a good option for elderly patients or those with liver disease as it lacks active metabolites, with doses of 2–4 mg every four to six hours. I recommend symptom-triggered dosing as a way to minimize overall benzodiazepine exposure (for more on symptom-triggered dosing, see Q&A with Dr. Ponce Martinez in this issue).

For all patients, I make sure to optimize non-benzodiazepine treatment options that they can continue to utilize once discharged. Antidepressants, such as escitalopram or venlafaxine, are first-line pharmacotherapy for anxiety disorders and are my first considerations in formulating a benzodiazepine-sparing regimen (Szuhany KL and Simon NM, JAMA 2022;328(24):2431–2445). Antipsychotics, specifically second-generation agents like olanzapine, are an effective alternative to benzodiazepines for managing agitation. These often act faster and produce a lower risk of oversedation than benzodiazepines (Amore M et al, Front Psychiatry 2021;12:628965). I also often prescribe gabapentinoids (gabapentin and pregabalin) for anxiety. When used short term, pregabalin appears as effective as lorazepam and has the added advantage of improving anxiety symptoms in cases refractory to antidepressants. The risk of withdrawal or rebound anxiety symptoms is minimal when discontinuing pregabalin following long-term use. Like pregabalin, gabapentin improves anxiety symptoms and enhances the therapeutic response to antidepressants. Gabapentin doses are 300–3600 mg per day, and pregabalin doses are 150–600 mg per day (Greenblatt H and Greenblatt DJ, Clin Pharmacol Drug Dev 2018;7(3):228–232).

CARLAT VERDICT 

Understanding a patient’s substance use history and their susceptibility to SUDs is crucial in making informed decisions about benzodiazepine use. If you need to prescribe benzodiazepines for withdrawal symptoms or acute anxiety/ agitation, keep the duration short and taper the medications prior to discharge. Don’t overlook alternative medications for treating anxiety, like second-generation antipsychotics, antidepressants, gabapentin, and pregabalin.