Benzodiazepine (BZD) tolerance and addiction affect all socioeconomic strata, exacerbated in part by outpatient providers who prescribe these drugs for anxiety and insomnia. Despite the availability of other treatments, the percentage of adults in the United States filling a BZD prescription has increased by 2.5% annually between 1996 and 2013 (Bachhuber, Hennessey, Cunningham, & Starrels, 2016). In addition, the quantity of BZD per prescription has tripled (Bachhuber et al., 2016). During this time period, there was a 4.3-fold increase in deaths from BZD overdose, either alone or in combination with opioids (National Institute on Drug Abuse [NIDA], 2018). The co-prescription of these two drugs approximately doubled from 2001 to 2013 (Sun et al., 2017). The overdose death rate continues to rise among ethnic minorities and older adults, despite stabilizing in other groups (Bachhuber et al., 2016).
An added concern is the appearance of high-potency “designer benzodiazepines,” which combine the properties of two different BZDs to yield a powerful new drug (Carpenter, Murray, Dunkley, Kazzi, & Gittinger, 2019; Høiseth, Tuv, & Karinen, 2016; Moosmann & Auwärter, 2018). For example, clonazolam is similar to alprazolam and clonazepam combined, but with much greater potency (Lembke, Papac, & Humphreys, 2018). Most designer BZDs were created (and rejected) by drug companies as potential new drugs to bring to market (Moosmann, King, & Auwärter, 2015). They are now sold in the illegal drug market.
Outpatient demand for fast relief of the painful symptoms of anxiety and insomnia is a pressure faced by providers (Limandri, 2018). Well-intentioned providers may prescribe a short course (<2 weeks) of BZDs as a “stop-gap” measure to bridge the time for a nonaddictive medicine to take effect (e.g., selective serotonin reuptake inhibitor [SSRI] antidepressant) or while the patient awaits an appointment with a behavioral health provider (L. Platt & N. Rajagopal, personal observation, 2018). However, some patients progress rapidly from initial prescription to dependence on the drug. Patients who are dependent on BZDs may have responded to non-addictive medications (e.g., hydroxyzine, gabapentin, SSRI antidepressants) (Stahl, 2017) or nonpharmacological methods of anxiety and insomnia management (e.g., cognitive-behavioral therapy-insomnia [CBT-I], mindfulness, psychotherapy) (Cook, Biyanova, Masci, & Coyne, 2007; Platt, Whitburn, Platt-Koch, & Koch, 2016).
Before tolerance and dependence develop, BZDs effectively alleviate symptoms of anxiety and insomnia. However, other serious side effects may appear, including confusion, falls, memory problems (Maust, Kales, Wiechers, Blow, & Olfson, 2016), and possible risk of dementia (Billioti de Gage et al., 2014; Park et al., 2018).
Tolerance, withdrawal, and addiction can occur in as little as a few weeks to a few months of regular BZD use (American Psychiatric Association [APA], 2009).
The literature is replete with criticism of BZD overuse (i.e., prescriptions for unnecessarily large quantities and/or for unjustifiable reasons) (National Institute of Mental Health [NIHM], 2014) and misuse (i.e., prescribed for wrong disorder and/or self-medication) (Brett & Murnion, 2015; Soyka, 2017) especially among older adults (Maust et al., 2016).
NIDA (2018) and the World Health Organization (Wanderley & Santos, 2015) have expressed concern about the growing use and misuse of BZDs, with resultant illnesses, accidents, addiction, and mortality (Bachhuber et al., 2016). Older adult patients comprise the largest portion of those taking BZDs and experience many of the negative sequelae of their chronic use (Maust et al., 2016; NIHM, 2014; Olfson, King, & Schoenbaum, 2015). Often these patients are not referred to a mental health provider until it becomes obvious they are dependent on or addicted to these medications.
Between 20% and 30% of long-term users become dependent on these drugs, and many find it impossible to withdraw (Lader & Kyriacou, 2016; Soyka, 2017). Once patients are addicted to BZDs, withdrawal can be difficult (Lader, 2011) because of severe discomfort from rebound anxiety and other symptoms (Liebrenz, Gehring, Buadze, & Caflisch, 2015). Abrupt cessation of the drug at higher doses can cause seizures (Soyka, 2017) or death (Brett & Murnion, 2015). Death is even more likely when BZDs are combined with other respiratory depressants such as opioids (Billioti de Gage et al., 2014; NIDA, 2018).
Leibrenz et al. (2015) conclude that long-time users of BZDs may need to be maintained on the drug because of inability to withdraw, analogous to treating people with opioid use disorder with methadone. Reeve et al. (2017) and Soyka (2017) note that there is no consensus on how to achieve out-patient BZD down-titration and cessation. Prescribers use a variety of techniques to minimize BZD use, including changing to a BZD with a longer half-life, using a slow down-titration schedule, and substituting a non-addictive drug with similar therapeutic actions (Brett & Murnion, 2015). Cook et al. (2007) suggest referral for psychotherapy to treat symptoms of anxiety and insomnia.
BZDs work well for outpatient anxiety and insomnia by binding to GABA receptors in the brain, producing an inhibitory effect and counteracting anxiety (Soyka, 2017). They act quickly compared to safer alternatives, such as SSRI antidepressants, which can take weeks to be effective. Patients like these drugs and many believe that nothing else will help them (Cook et al., 2007). Hill, Van Oostrum, Conroy, and Towle (2015) report that providers felt intimidated by patients who demand these drugs. As part of the National Health Service Addiction Services in Lanark-shire, United Kingdom, guidelines were developed to help prescribers who have training (RCGP Certificate in Substance Misuse) in the safe reduction and discontinuation of BZD (Table 1). The authors believe these guidelines helped providers feel supported in their decision to deny BZDs to patients or to insist on tapering. This finding was evidenced by a decrease in prescriptions written for BZDs and the total quantity prescribed within the first 12 months of the guidelines' introduction (Hill et al., 2015).
Summary of Guidelines for Benzodiazepine (BZD) Discontinuation, National Health Service Addiction Services in Lanarkshire, United Kingdom
Evidence-based alternatives to treat anxiety and insomnia include SSRI and serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressants, alpha-2 agonists, beta-blockers, some antihistamines, some anticonvulsants, psychotherapy, CBT-I, mindfulness meditation, and yoga (APA, 2009; Baldwin et al., 2005; Maust et al., 2016; Platt et al., 2016; Taylor & Pruiksma, 2014).
Academic and Pharmaceutical Detailing
The current quality improvement project represents an attempt to decrease BZD prescription writing by providers. An educational approach combining academic detailing, an evidence translation method, and pharmaceutical detailing, a technique widely used by pharmaceutical companies to encourage prescription of branded drugs, was used to influence provider prescribing behavior.
Academic detailing provides unbiased, evidence-based information to providers using an individualized, interactive approach. It has been successfully used to disseminate best practice information to providers in various settings (Bounthavong et al., 2017; Chhina et al., 2013; National Resource Center for Academic Detailing, n.d.).
Pharmaceutical detailing has been a staple of drug companies for decades, used to influence providers to prescribe brand name drugs (Avorn, 2017; Chung, Kim, & Park, 2017; Sah & Fugh-Berman, 2013). Common drug promotion techniques include sales calls to providers with distribution of complimentary drug logo merchandise (e.g., pens, sticky notes, coffee mugs, penlights, t-shirts) and educational offerings with provision of complimentary food to providers. Academic detailing was developed in reaction to the product-promotion detailing visits of pharmaceutical salespeople (Avorn, 2017; O'Brien et al., 2007).
Evidence-Based Practice Question
Consistent with the Johns Hopkins Nursing Evidence-Based Practice Model (Dearholt & Dang, 2012), a PICOT question was created for this project:
When providers working at a large Midwestern university outpatient clinic (P) receive a 4-week educational intervention (I) compared to occasional e-mails and informal “brown bag” talks about deprescribing (C), do providers write fewer BZD prescriptions (O) in the 30-day period following the intervention (T)?
Institutional Review Board Review
The university Institutional Review Board (IRB) determined that the nature of the current project was quality improvement and does not meet the definition of human subject research.
An outpatient clinic was sought to serve as the site for an intervention designed to discourage providers from prescribing BZDs. The university clinic used in the current project was chosen because of the medical director's interest in decreasing the number of BZD prescriptions written by providers (i.e., advanced practice RNs [APRNs], MDs, residents), and willingness to facilitate implementation of the project.
Two academic detailing meetings (separated by 4 weeks) with approximately 30 salaried and resident clinic providers were held during regular continuing education/administrative time. Depending on the time of day, breakfast or lunch was provided. Two posters listing harm reduction strategies and alternative treatments for anxiety and insomnia were hung in the provider office area (Figure 1). Mugs and pens with the “No Benzo” logo were distributed to all who attended these meetings. Extra merchandise was left in the clinic for those providers who were absent as well as clinic nursing staff.
“No Benzo” posters used in the clinic for the intervention.
Note. CBT = cognitive-behavioral therapy; SSRI = selective serotonin reuptake inhibitor; PRN = pro re nata (as needed); QHS = daily at bedtime; QID = four times daily; TID = three times daily; BID = twice daily. Alpha-2 agonists, beta-blockers, and some anticonvulsants are used off-label for anxiety and insomnia.
The initial provider meeting comprised an evidence review of BZD dangers, discussion of harm reduction strategies, and problem-solving using case examples generated by providers. The follow-up meeting, which took place 30 days later, was an informal discussion of provider experience in the intervening month and validation of positive change (e.g., deprescribing behavior, conversations with patients about BZD use, consideration of down-titration schedules).
Data Collection and Analysis
Because medically supervised out-patient withdrawal from BZDs is a slow process, the authors believed it was unrealistic to expect the amount of BZDs prescribed at this clinic to drop dramatically, even if providers were highly motivated. In addition, these providers were knowledgeable about the growing BZD problem in the United States and the importance of judicious use of these drugs. Using this reasoning, a 1% reduction in BZD prescriptions postintervention was used as the measure of success.
Because five different generic BZDs with varying potencies were used at this clinic, it was necessary to find a way to quantify the amount of BZDs being prescribed. Using a chart of BZD equivalencies (Table 2), each prescription was converted to a common denominator: the diazepam-equivalent (DE) dose. This conversion made for ease of comparison of BZDs prescribed pre- and postintervention.
Equivalency Chart of the Clinic's Formulary Benzodiazepine with Diazepam
Clinic BZD prescription information was extracted from the electronic medical record by hospital information systems for two periods: 12 months preintervention (calendar year 2017), and 30 days postintervention. The pre-intervention monthly average DE was calculated and compared to the 30-day postintervention DE. The outcome measure was the numeric difference in the prescribed DE pre- and postintervention. The mathematical difference showed the direction of change.
In the 12 months prior to the intervention, DE were prescribed at an average monthly rate of 36,434 DE. In the 30-day postintervention period, the number decreased to 7,290 DE.
A simple formula was used to calculate the numeric change in DE prescribed from pre- to postintervention: A – B = C, where A = pre-intervention prescribed DE monthly average, B = 1-month postintervention prescribed DE, and C = change in DE prescribed following intervention. When the formula was applied, a major decrease in the number of prescribed DE was noted:
A second formula, C/A × 100 = D, was used to express the percent decrease (D) in DE prescribed following the intervention: 29,144/36,434 × 100 = 80% reduction in DE postintervention.
BZD overuse and misuse are growing concerns in the United States. Efforts to discourage providers from prescribing BZDs to outpatients will help address this public health problem. Following this quality improvement intervention, there was an 80% decrease in BZDs (measured in DE) prescribed by all clinic providers in the 30-day postintervention period when compared to the monthly average during the 12-month preintervention period.
The decrease in prescribed DE was greater than anticipated, and it appears that the combination of academic and pharmaceutical detailing had a significant effect on providers' prescribing behavior. Others have reported that properly implemented academic detailing can be successful in modifying provider prescribing behavior (Bounthavong et al., 2019; Ndefo, Norman, & Henry, 2017; Trotter Davis, Bateman, & Avorn, 2017). The current intervention combined academic detailing with the marketing staple, pharmaceutical detailing.
To better understand the effect of the combined detailing intervention, a brief online postintervention survey was e-mailed to all participating providers (N = 30). Of interest were elements of the intervention that had the most impact on prescribing behavior. There was a 13% response rate to the survey (4/30). The majority of respondents (3/4) said the evidence-based alternatives to BZDs suggested during the intervention and delineated in posters hung in the provider office area (Figure 1) influenced their prescribing practices. Repeated attempts were made to elicit feedback from survey non-responders but were unsuccessful. The low response rate makes it difficult to say with assurance that the dramatic drop in BZD prescribing was due primarily to the intervention.
Other plausible explanations for the decrease are provider turnover, university educational programs, and recent media coverage of the BZD crisis in the United States. It is possible that some patients chose to leave the practice when told that they would be weaned off BZDs, contributing to the decrease in prescribing.
Although providers did not say they were influenced by the “No-Benzo” logo merchandise, many appeared excited to receive the coffee mug and pens. Miller (2007) noted that it is typical of physician providers to minimize the influence of “product merchandise” on their decision-making process.
Other than using these treatment alternatives, it is not clear what measures providers used to prevent the discomfort and danger of BZD detoxification in clinic patients. It is important to assure that patient safety was not compromised by this decrease in BZD prescribing, because a sudden withdrawal from high doses can be life-threatening (Soyka, 2017). Various down-titration schedules were discussed (Shohel et al., 2013) as well as the need for frequent monitoring of patients as they decrease their BZD intake.
It is possible that some patients were being down-titrated with smaller doses for fewer days (e.g., 15-day vs. 30-day prescriptions). Prescribing patterns changed postintervention, such that it was rare to see large amounts of BZDs prescribed, and there were often no refills. This finding was in sharp contrast to prescribing patterns preintervention. It is possible that providers asked patients to return to the clinic more often for closer management. One could then expect to see a larger number of prescriptions being written, but for smaller amounts of drug and no refills. Data collected in the future will be examined for this pattern.
Whether this change in provider behavior will be sustained over time or gradually return to original prescribing practices remains to be seen. To address this question, measurements of BZD prescribing will be taken every 30 days for 6 months following the intervention. A percentage of providers will have finished their family practice residency, to be replaced by new residents. It will be interesting to see if the clinic culture has changed with regard to BZD prescribing, or if the prescription numbers will trend upward again.
Implications for Nursing
Nurses are educated in teaching methods and use them often when caring for patients, or with colleagues. APRNs can make a difference in out-patient provider prescribing behavior. With the support of clinic administrators, APRNs can lead educational interventions, such as the one described in the current article, as well as spe ak individually to colleagues about deprescribing BZDs. Staff nurses can reinforce the “No Benzo” message with patients by discussing self-help treatments, such as yoga and meditation, as well as reinforcing the dangers of BZDs. As a result, APRNs and RNs can positively impact the morbidity and mortality of outpatients with anxiety and insomnia.
The United States is in a BZD crisis similar to the country's opioid crisis. It is important to educate patients and providers about the dangers of BZDs and the need to use safer methods for anxiety management and treatment of insomnia. The current quality improvement project attempted to impact provider prescribing behavior by using two education methods. Combined academic detailing and pharmaceutical detailing may have influenced providers to prescribe fewer BZDs. Further examination of the impact of the intervention on clinic providers may answer questions about the size and sustainability of the response, as well as the effect on patient treatment and safety.
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Summary of Guidelines for Benzodiazepine (BZD) Discontinuation, National Health Service Addiction Services in Lanarkshire, United Kingdom
|Develop a care plan with the patient and multidisciplinary team|
|Convert all BZDs to an equivalent dose of diazepam (long half-life and less severe withdrawal)|
|Prescribe BZDs on a reduction schedule when all non-prescription options have not succeeded|
|While weaning BZD, continue psychological, self-help, and family support|
|Pace of reduction should be based on patient's ability to tolerate withdrawal|
|Avoid adjuvant treatment but may use beta-blocker for “prominent sympathetic over activity” (Conroy & Hill, 2016, p. 87) or antidepressant for clinical depression|
|Reduce dose 1/8 of daily dose (range 1/10 to 1/4) every 2 weeksa|
Equivalency Chart of the Clinic's Formulary Benzodiazepine with Diazepam
|Drug||Dose (mg)||Potency Factor|