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Amid the opioid crisis in the United States, another class of psychoactive medications — benzodiazepines — is often used inapropriately and should be considered for deprescribing. In tapering these medications, safe practices must be adopted and nonpharmacological alternatives should considered, when appropriate.
In the late 1990s, U.S. health care providers began to prescribe opioid pain relievers in increasing amounts after pharmaceutical companies assured them that patients would not become addicted. These opioid prescribing practices led to widespread misuse of both prescription and nonprescription opioids, and the ensuing realization among the medical community that these medications were indeed addictive. In 2017, the U.S. Department of Health and Human Services (HHS)declared a public health emergency and announced a strategy to combat the opioid epidemic (“What Is the U.S. Opioid Epidemic?” Sept. 4, 2019; http://bit.ly/2uQnlNR).
In October 2019, HHS published guidelines for appropriate dosage reduction or discontinuation of long-term opioid analgesics, which provide advice to clinicians who are considering making a change to a patient’s opioid dosage (“Guide for Clinicians,” Oct. 2019; http://bit.ly/2su87gI).
The Comprehensive Addiction and Recovery Act (CARA) of 2016 included provisions that give Medicare Part D plans important new tools to use in 2019 to address opioid overutilization. To execute this law, the Centers for Medicare & Medicaid Services (CMS) passed a regulation so that Part D plans may create a drug management program. This program limits access to certain controlled substances that have been determined to be “frequently abused drugs” for patients who are considered to be at-risk for prescription drug abuse. Limiting access means that a patient might only be able to obtain these medications from a specified prescriber or pharmacy.
In 2019, CMS identified both opioids and benzodiazepines (BZDs) as frequently abused drugs (MNL Matters, SE18016, Nov. 1, 2018; https://go.cms.gov/35WbBWO). A 2018 study indicated that 12.6% of U.S. adults reported BZD use in the past year, with misuse accounting for 17.2% of overall use. The incidence of BZD use among people aged 65 to 80 has been estimated at 8.7%, and misuse was reported in 0.6% of the ≥65-year-old population, the lowest of all the age ranges studied (Psychiatr Serv 2019;70:2,97–106).
In the skilled nursing facility population, it is not uncommon for patients to be admitted who have been taking a BZD for years or even decades. In the United States, more than 10% of women and 6% of men aged 65 to 80 have filled at least one prescription for BZDs in a one-year period; approximately one-third of them have received BZDs for longer than 120 days in a year (JAMA Psychiatry 2015;72:136–142).
Development and Effects of Benzodiazepines
The grandfather of all BZDs, chlordiazepoxide (Librium), was identified in 1955 by a chemist at Hoffmann-La Roche pharmaceuticals. The company marketed it and continued to research modified molecules for enhanced activity, and more new BZDs came on the market. Less than two decades later, BZDs were the most frequently prescribed class of medication in the United States (Consult Pharm 2013;28:538–548).
It took 15 years for researchers to discover that BZDs worked by affecting gamma-aminobutyric acid (GABA), which raised concerns about the potential for abuse and dependence. Subsequently, guidelines began to be developed for appropriate and cautious use.
Older adults experience a lesser therapeutic response to BZDs compared with young and middle-aged adults, and they have heightened sensitivity to the side effects. Both short-acting (e.g., triazolam) and long-acting (e.g., diazepam) BZDs have been included in the Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults since its original publication in 1991. Older adults have an increased sensitivity to all BZDs and a decreased metabolism of the long-acting agents. Long-acting BZDs cause prolonged sedation and increase the risk of falls in the elderly, and the criteria specifically state that “in general, all benzodiazepines increase risk of cognitive impairment, delirium, falls, fractures, and motor vehicle crashes in older adults.” Hence, the recommendations are to avoid use of these medications when more appropriate alternatives are available (J Am Geriatr Soc 2019;67:674–694).
Physicians prescribing BZDs to older patients should provide education about the potential side effects and the risks associated with their use. In the case of long-term use of BZDs, tapering protocols should be discussed. Several pharmacological (non-BZD) and nonpharmacological alternative options are available for treating insomnia and anxiety in older adults. Treatment with BZDs should be avoided for this population when safer alternatives are an option (Mayo Clin Proc 2016;91:1632–1639).
In the “Final Call Letter,” for calendar year 2019 (Apr. 2, 2018; https://go.cms.gov/2FLOKma), CMS announced that new safety edits for opioids and BZDs applied to all Medicare beneficiaries filling prescriptions under the Medicare D benefit, beginning January 1, 2019. These edits adopted by Medicare D Plan sponsors were implemented at the point of sale and included:
Soft edit for concurrent opioid and BZD use
Soft edit for duplicative long-acting opioid therapy
Care coordination edit at 90 morphine milligram equivalents (MME)
Hard edit at 200 MME or more (optional), and
Hard edit seven-day supply limit for initial opioid fills (opioid naïve)
Soft edits are rejects that can be overridden by the dispensing pharmacist at the point of sale using a series of override codes. Hard edits require the pharmacist to call the plan’s help desk for an override and answer questions to determine whether the prescription is necessary and safe for the patient to take.
Of note, the first safety edit applies to the concurrent use of an opioid and a BZD. With this opioid-BZD soft edit from CMS — and considering elderly patients may have prolonged use of BZDs — pharmacists and prescribers are questioning how to proceed with patient care. Patients aged 65 and older are sensitive to the side effects of BZDs, but abrupt discontinuation could be harmful or even fatal.
Currently there is no gold standard for a tapering algorithm for BZDs, but an internet search of medical resources can provide several options. The one commonality among them all is that this discontinuation must be done gradually.
When to Taper
For elderly nursing home residents, inappropriate or unnecessary BZD use should be identified and a tapering plan developed together with the patient. Tapering can be challenging because some patients may experience both physical and/or psychological withdrawal symptoms. It is important to perform a thorough review of the patient’s history, including the type of BZD prescribed (short or long acting) and the dose, frequency, and duration of use. An accurate history needs to be obtained to determine whether the patient has ever tried a BZD taper and the details of the attempt.
Chinyere Ogbonna, MD, MPH, of Kaiser Permanente, San Jose, and Anna Lembke, MD, of the Stanford University School of Medicine in California have published specific BZD tapering guidance (Am Fam Physician 2017;96:606–608). A BZD taper should be considered for any patient taking BZDs daily for longer than one month. This is especially the case for those who are:
Older than 65 years (because of the risk of injury from falls and other cognitive adverse effects)
Taking multiple BZDs, BZDs combined with prescribed opioids or amphetamines, or supratherapeutic dosages
Cognitively impaired, have a history of traumatic brain injury, or current/history of substance use disorder, especially sedative-hypnotic or alcohol-use disorder
Drs. Ogbonna and Lembke note that a good starting point is educating the patient and discussing the adverse effects of long-term BZD use, particularly among older adults.
The U.S. Department of Veterans Affairs (VA) also has published guidance for tapering BZDs as it relates to the treatment for post-traumatic stress disorder (PTSD) in both younger and older veterans (“Effective Treatments,” National Center for PTSD, 2015; http://bit.ly/30k5g6t). They note that switching to a longer acting BZD may be clinically appropriate to assist with the taper.
The guidance published by the Psychopharmacology Unit of the University of Bristol, Bristol, United Kingdom, recommends converting all BZDs to an appropriate dose of diazepam, which has a long half-life, and then reducing the dose by one-eighth every two weeks (Br J Clin Pharmacol 2014;77:302–314). However, diazepam is included in the Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults. Due to its long half-life and its side effects of increased sedation and risk of falls, diazepam may not be the drug of choice for tapering BZDs in older adults (J Am Geriatr Soc 2019;67:674–694).
The BZD taper should take place over several weeks or months, and the dose should not be reduced faster than 25% of the total daily dose each week. The PTSD guidance from the VA states for therapeutic bedtime doses to reduce the total daily dose by 25% weekly but to anticipate rebound insomnia. It is recommended to discuss good sleep hygiene habits with the patient and to have a plan for a non-BZD therapy to be initiated if necessary (“Effective Treatments,” National Center for PTSD, 2015; http://bit.ly/30k5g6t).
For daytime dosing (one to four times daily), the initial taper should be between 10% and 25% of the total daily dose, with subsequent tapers individualized based on the patient’s response. Further reductions of 10% to 25% weekly are well tolerated pharmacologically. Maintaining the patient on a 50% dose for one to two months may be warranted before proceeding further with the taper. For patients on concurrent opioid and BZD therapy, consider tapering one or both medications.
Prolonging the BZD taper longer than six months may worsen long-term outcomes, and patient education about anxiety management and coping is essential for a successful taper. Engage the interdisciplinary health care team to provide support whenever possible.
Nonpharmacological treatments are key for a successful BZD taper, so they should be included in the patient’s treatment plan. The health care team can assist patients with the challenges they may face when tapering off a BZD (Curr Psychiatr 2019;18:9–10):
Validate the patient’s concerns.
Reassure patients that support will be provided throughout the taper.
Provide additional support resources.
Educate the patient about the tapering process and symptoms of withdrawal.
Recommend nonpharmacological therapies such as cognitive-behavioral therapy, motivational interventions, and development of coping skills.
Involve the patient’s family and friends for support and encouragement.
Keep a positive and encouraging attitude and be patient. Remember 70% to 90% of patients can be successfully tapered off of a BZD, and several different tapering strategies have been shown to be effective.
Every tapering plan should be tailored to the individual patient. Recurrence or rebound symptoms may occur as early as a few days to one week, but if the care team is educated about monitoring for these symptoms, alternative treatments can be initiated quickly and the process with be successful.
Dr. Manzi has been a licensed pharmacist since 1990 and a Board Certified Geriatric Pharmacist since 1998. She is currently a clinical advisor for CVS/Caremark, coordinating with account teams and health plans on the details of their pharmacy benefit offerings, formulary implementation, medication utilization management, and MTM as well as providing clinical information and geriatric expertise. Any opinions in this article are that of the author and not of CVS/Caremark.