Abstract
Though clinical guidelines and policies discourage the chronic prescribing of benzodiazepines, rates of prescribing have continued to rise in the United States with an estimated 65.9 million office visits per year made for this purpose. Quietly, we have become a nation on benzodiazepines. There are numerous reasons for this discrepancy between official recommendations on the one hand, and actual clinical practice on the other. Drawing from the literature, we argue that while patients and providers both shoulder some of the responsibility, they cannot be solely blamed. Rather, policies and guidelines regarding benzodiazepine prescribing have become out of touch with the clinical reality that benzodiazepines are now deeply entrenched in modern medicine. We propose that guidelines regarding benzodiazepines need to reconsider how to apply concepts such as harm reduction and other lessons learned in the opioid epidemic in order to help physicians manage this increasingly pressing problem affecting millions of Americans.
Chronic benzodiazepine use has been labeled a “hidden epidemic,” not because it is a secret but rather because of the surprising lack of attention it garners. 1 Benzodiazepines have been implicated in a number of serious adverse effects, including cognitive and psychomotor impairment, increased fall risk, dependence, and seizures. 2 Furthermore, benzodiazepines can be fatal, whether due to withdrawal-induced seizures, or due to overdose (with or without other sedatives such as alcohol and opioids). 3 Indeed, in 2022 benzodiazepine involvement in fatal opioid overdoes reached a rate of nearly one in six. 4
While benzodiazepines can play a critical and sometimes life-saving role in the treatment of conditions such as acute alcohol withdrawal and panic disorder, professional organizations and regulatory agencies have recommended against long-term use. The US Food and Drug Administration (FDA) requires a black box warning for benzodiazepines, 5 the American Geriatrics Society recommends against benzodiazepine use in individuals over 65 years of age, 6 and the United Kingdom National Institute for Health and Care Excellence (NICE) recommends benzodiazepines only as a “short-term measure during crises.” 7
Despite this, benzodiazepine prescribing has continued to rise over the last 20 years. The outpatient benzodiazepine visit rate in the United States doubled between 2003 and 2015, (from 3.8% to 7.4%) 8 and in 2016, 4.3% of respondents to the National Survey on Drug Use and Health reported using prescription benzodiazepines. 9 Furthermore, chronic benzodiazepine use, as opposed to short-term, is common: 89% of visits in 2014-2016 during which a benzodiazepine was prescribed were for continuing, rather than new, scripts. 10
In pop culture, benzodiazepines have become so ubiquitous as to have become literal punchlines, from Leonardo DiCaprio in the film Don’t Look Up playing a protagonist who jokes on national television about taking Xanax, to the show The Bear, in which a group of rowdy children are accidentally drugged when a bottle of alprazolam falls into the punch. The father’s response to the sudden peace and quiet: “I kinda like it.” 11 As of 2016, benzodiazepines were being prescribed in an estimated 27 annual visits per 100 adults, or a staggering annual average of 65.9 million office-based physician visits. 10
How did we become a nation on benzodiazepines?
Some physicians strive to limit prescribing of benzodiazepines, and indeed, there can be tremendous variation between individual providers, wherein the top quartile of providers in one study were found to prescribe benzodiazepines at an intensity 6.5 times greater than the bottom quartile. 12
Nevertheless, the problem does not appear to solely lie within a few “bad apple” prescribers. Benzodiazepines are typically acknowledged to be widely prescribed in general practice. 13 Furthermore, benzodiazepines are problematic in multiple specialities. In a study of prescribing practices between in 2014-2016, benzodiazepines were prescribed in ∼31,000 primary care visits annually, ∼9,300 psychiatry visits, and co-prescribed with opioids in ∼1,270 orthopedic visits annually. 10 Proceduralists are at risk, too: among benzodiazepine-naïve patients prescribed a perioperative benzodiazepine in a study spanning 2009-2017, the rate of progression to persistent benzodiazepine use postoperatively was ∼20%. 14
Do prescribers need better awareness of the risks of chronic benzodiazepine treatment? Unfortunately data suggests that, despite knowing the risks, providers often continue to prescribe. 15 Indeed, if the numbers are to be believed, many of us are in fact doing this.
Exploring the reasons why providers prescribe benzodiazepines long-term is not to assign blame, but rather to acknowledge what multiple studies have found: that the underlying drivers are incredibly complex and tenacious. 15 To begin with, providers have limited time to address problems, and talking to patients about benzodiazepines can be extremely challenging. It has been noted that patients can become emotionally attached to benzodiazepines, 16 causing them to react strongly to suggestions of tapering. Even when informed of the risks, patients have been reported to sometimes disregard or minimize issues. 16
Another contributor is the perception, both among providers and patients, that people on chronic prescriptions are stable without adverse effects. In one study, as many as 46% of the physician respondents endorsed agreement with this statement. 17 Patients, too, may endorse that they are “dependent” while denying being “addicted,” the implication being that long-term benzodiazepine use is not problematic. 16
In the face of these headwinds, deprescribing benzodiazepines becomes exceptionally arduous. Providers commonly report an experience of starting a benzodiazepine taper, only for it to end in patient distress, demoralizing failure, and/or resumption of the prior dose. 15 The very topic of benzodiazepines becomes daunting and dreaded. Thus many prescribers ultimately decide that deprescribing benzodiazepines is simply a low priority compared to the myriad other health problems they must address.15,17 Put crudely, though benzodiazepines are not the preferred option compared to first-line therapies such as an SSRI plus cognitive behavioral therapy, they can come to appear as a “lesser evil.”
How do we respond?
Current guidelines continue to generally recommend limiting prescribing of benzodiazepines to brief 2-4 week treatment windows, preferentially in the context of acute crisis. 7 However while prescribing of benzodiazepines for “2-4 weeks only” is an admirable goal, it can be impractical, especially in primary care or mental health.
The main issue in deprescribing benzodiazepines is the prescriber’s lack of options between the extremes: on the one hand are a slew of unproven interventions which suffer from low efficacy rates, on the other, the proverbial “kicking the can down the road” and continuing to prescribe. Stopping a benzodiazepine abruptly in a patient with dependence is not advised given the risk of withdrawal symptoms, including seizures.
To begin with, deprescribing benzodiazepines starts with treatment of the anxiety, panic, and insomnia disorders which often underlie chronic benzodiazepine use. Front-line, evidenced-based pharmaco- and psycho- therapies such as SSRIs, SNRIs, CBT, and mindfulness should be the foundation of any treatment approach to these conditions. However, even when front-line therapies are being utilized, deprescribing the benzodiazepine can still constitute an immense challenge.
The mainstay approach in the outpatient setting for chronic benzodiazepine use is gradual dose reduction (GDR), recommended by >90% of review articles and clinical practice guidelines. 18 However GDR practices themselves exhibit significant heterogeneity within the literature: time frames, taper rates, and medication of choice (e.g., switching to a long-acting benzodiazepine such as diazepam) can all vary. Critically, so do success rates. 18 In our experience, few patients “enjoy” GDR, and a high level of motivation is frequently required to complete the process successfully.
Pharmacologically, we also have minimal proven treatments. 19 Carbamazepine, flumazenil, propranolol, and melatonin are among the most studied, with carbamazepine showing some potential to assist taper completion and withdrawal symptoms.20,21 However, findings are heavily mixed, with a general scarity of randomized control trials. 18 Limited theoretical understanding of how these medications interact with benzodiazepine withdrawal contributes to heterogeneous approaches to the problem.18,21
Psychological therapies have been recommended to facilitate benzodiazepine deprescribing, sometimes in concert with other approaches. Therapies generally include CBT, anxiety management, stress management, and brief in-office psychological interventions. 18 Similarly though, results have not yielded clear best practices.
In the inpatient setting, tapers can be completed more rapidly, e.g., in as brief a time period as three days. 22 Phenobarbital has been reported to have efficacy in this setting, 23 as have flumazenil infusions, 24 but these practices are not widespread as of now, and current evidence is somewhat limited. Furthermore, as with alcohol and opioid use disorders, inpatient “detoxifications” are useful for managing the risks of acute withdrawal and intoxication, but they are unfortunately much more limited in addressing the drivers of chronic use.
Given so few proven interventions to effectively facilitate the discontinuation of benzodiazepines, the question of chronic maintenance on benzodiazepines arises. This remains a highly controversial approach, and is generally considered a strategy of last resort. In our experience, benzodiazepine maintenance can also be a question of harm reduction. There are a small number of limited studies in which maintenance therapy was considered “successful,” e.g., preventing non-prescribed benzodiazepine use. 25 Ultimately, with certain patients (such as those who have had multiple unsuccessful discontinuation attempts or cannot tolerate taper and withdrawal), providers may have to make their own determinations as to each patient’s holistic risks and benefits.
As evidenced by the rising tide of prescriptions, the current approach is unsustainable. Although we have discussed interventions that providers can take, one crucial modality is missing: institutional interventions. We applaud institutions attempting to challenge combat chronic benzodiazepine use, for example by educating clinicians on alternatives to benzodiazepines, publishing detailed guidelines, or utilizing prescription monitoring databases. However more often than not, individual providers are on their own when it comes to managing benzodiazepines. Faced with the demands of modern scheduling, the lack of effective treatments, and numerous other health concerns competing for their time, it is easy to see why many providers would de-prioritize benzodiazepine tapering.
We suspect that reducing chronic benzodiazepine use will require broader institutional efforts to provide the resources and research to address this “hidden epidemic.” For example, would providers benefit from support staff, e.g., similar to diabetes coaches, to follow and reassure patients undergoing GDR? Can proper referrals to addiction specialists be streamlined? What training, if any, would help providers navigate extremely difficult conversations with patients about benzodiazepines?
The Hub and Spoke Model, pioneered in 2013, is a systemic approach to the opioid epidemic involving regional centers (“hubs”) which provide specialized services and support for local clinics (“spokes”). 26 Although the Hub and Spoke Model has not been successful in all states, 27 states such as Vermont and Washington have reported large increases in the number of patients prescribed medications for opioid use disorder.26,28 Opioid use disorder is very different from Sedative-Hypnotic use disorder—for one, there is no equivalent to buprenorphine for benzodiazepines. However the creation of state-wide networks of addiction specialists supporting front-line staff may help disseminate best practices and support providers through what can be a very challenging interactions with patients, with the ultimate goal of helping them feel more empowered and less isolated.
Conclusions
Though the risks of chronic benzodiazepines have been known for decades, recent data suggests that long-term prescribing practices are not just persisting, but growing. Multiple structural factors are likely at fault: providers frequently lack the time, tools, and expertise to deprescribe successfully, patients can become emotionally attached to their medication, and the tenacious perception among both patients and providers that benzodiazepines are “safe” all contribute. What seems clear however is that expecting individual providers, oft-stressed and alone, to “hold the line” by themselves on benzodiazepines is impractical and unrealistic. Rather, institutions need to determine how to best support their providers through the challenge of deprescribing, whether it is at an organizational, state, or federal level. As the overall benzodiazepine death rate grew by 42.9% from 2019 to 2020, 29 we submit that these efforts are indeed worthy endeavors.
Footnotes
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
