Although the opioid epidemic has captured headlines, its crippling underbelly is the long-term use and abuse of benzodiazepine drugs. The number of prescriptions for benzodiazepine medications increased 67% between 1996 and 2013 (Bachhuber, Hennessy, Cunningham, & Starrels, 2016). U.S. surveillance data for 2013 identified the number of individuals seen in emergency departments because of opioid drug misuse/abuse increased 153% since 1999; the number of individuals treated for consequences of benzodiazepine medications rose 124% (Paulozzi, Strickler, Kreiner, & Koris, 2015). The death rate from drug overdose due to opioid and benzodiazepine concurrent drug use increased two-fold in all eight states studied. The eight states represented all regions of the United States; Louisiana was the highest in overall drug classes, whereas California rated the lowest. Women have higher rates of opioid and benzodiazepine drug use than men in all states, with the peak prescribing rate for benzodiazepine medications in the 65 and older population; approximately one half of these patients received prescriptions for benzodiazepine and opioid medications from the same prescriber on the same day (Hwang et al., 2016; Paulozzi et al., 2015). In fact, the ratio of women to men in benzodiaz epine drug prescriptions is 3:2, and women ages 41 to 50 and 71 to 80 receive the bulk of prescriptions for depression, anxiety, and insomnia (Dhahan & Mir, 2005). These statistics are consistent in other studies in the United States as well other countries. Most (50% to 80%) benzodiazepine drug prescriptions are issued by multiple prescribers and without direct prescriber–patient contact (i.e., refilled telephonically or as part of continuity of care from another prescriber) (Bjørner & Laerum, 2003; Okumura, Shimizu, & Matsumato, 2016).
Benzodiazepine medications are indicated for the treatment of anxiety and insomnia. Non-benzodiazepine drugs (also called Z-drugs) and melatonin receptor agonist agents have somewhat replaced benzodiazepine medications for insomnia, and although they can also be abused, discussion of this drug class will be discussed in another column. Prolonged use of benzodiazepine drugs results in downregulation of the GABA receptor, an adaptation that results in agonist receptor response changing to an inverse agonist, thereby making the mechanism of action the reverse of what is intended (Konopka, Wysiecka, & Samochowiecz, 2016). Therefore, long-term use of benzodiazepine medications results in adverse effects, including depression, emotional blunting, ataxia, aggression, irritability, nervousness, sedation, and cognitive impairment, such as loss of sustained attention, decreased verbal learning and memory, and visuomotor and visuoconceptual difficulties (Barker, Greenwood, Jackson, & Crowe, 2004; Schatzberg & Nemeroff, 2017). Even with short-term use of these medications, there are risks of falls, overdose, suicide, and vehicle crashes (Dowell, Haegerich, & Chou, 2016).
Patient and Prescriber Factors
Across many studies, patients most likely to be inappropriately prescribed benzodiazepine medications were older women (age >65 years) who lived in urban areas and had depression (Alessi-Severini et al., 2016; Ferries et al., 2017; Hwang et al., 2016; Maust, Kales, Wiechers, Blow, & Olfson, 2016). Comorbid conditions included anxiety, insomnia, substance abuse, tobacco use, osteoporosis, chronic obstructive pulmonary disease, alcohol abuse, sleep apnea, and asthma—conditions that potentiate adverse reactions to benzodiazepine drugs (Kroll, Nieva, Barsky, & Linder, 2016; Okumura et al., 2016). Co-prescribing opioid drugs added further risk, occurring at an increased rate from 2006 to 2012. During this period, 2.7% of emergency department encounters resulted in concurrent prescriptions of opioid and benzodiazepine medications, accounting for an increase from 6.8% to 9.6% (Hwang et al., 2016; Kim, McCarthy, Mark Courtney, Lank, & Lambert, 2017). In 2016, the U.S. Food and Drug Administration added a black box warning against prescribing benzodiazepine drugs with opioid medications.
Benzodiazepine drugs have beneficial uses if they are prescribed within their pharmacological limits (i.e., prescribed over a period of no more than 2 to 4 weeks, as withdrawal syndrome occurs thereafter) (Schatzberg & Nemeroff, 2017). In addition, short-acting benzodiazepine medications are recommended over long-acting medications to mitigate the risk of dependency (Bushnell, Stürmer, Gaynes, Pate, & Miller, 2017). However, in a large retrospective descriptive study, 25% of patients prescribed benzodiazepine medications were taking long-acting agents (Olfson, King, & Schoenbaum, 2015). In this same study, primary care providers prescribed benzodiazepine medications increasingly with patient age (2.6% in patients ages 18 to 25, 5.4% in patients ages 36 to 50, 7.4% in patients ages 51 to 64, and 8.7% in patients ages 65 to 80), whereas the reverse was true for psychiatrists (15% in patients ages 18 to 35 and 5.7% in patients ages 65 to 80) (Olfson et al., 2015).
A common practice is to prescribe a benzodiazepine drug concurrently with an antidepressant agent when initiating treatment for depression to hasten the antidepressant effects and reduce anxiety; however, a large randomized controlled study found no meaningful difference in treatment outcomes after 6 months and throughout the 2-year study (Bushnell et al., 2017). Furthermore, 12.3% continued the benzodiazepine medication over the 2-year period (Bushnell et al., 2017).
Ultimately, patients are experiencing the effects of anxiety, depression, and difficulty sleeping. They want immediate results and the ability to restore balance in their lives. The desire for immediate relief invites clinicians to find the fastest route to reduction of symptoms, but this immediate route is elusive considering the accompanying risks. It is difficult to sit with a distressed patient and suggest strategies that require weeks or months to achieve positive outcomes; hence, it is not surprising that clinicians resort to prescribing benzodiazepine medications as the first and only treatment.
What are the prescriber variables involved in benzodiazepine medication prescribing? General internal medicine physicians are more likely than family practice physicians to prescribe benzodiazepine drugs to treat patients with anxiety and depression alone and with combined anxiety and depression (Brieler, Scherrer, & Salas, 2015), and primary care providers preferred benzodiazepine medications more often than mental health providers (Hawkins et al., 2017). Advanced practice nurses were more likely to prescribe benzodiazepine medications in states with collaborative physician practices than those with independent practices (Schirle & McCabe, 2016). In general, family practice prescribers were aware of the risks and benefits of benzodiazepine medications in treating anxiety, depression, and insomnia, but did not perceive it within their role to consider nonpharmacological means of treatment or experienced barriers in implementation, such as time commitment and availability of resources (Anthierens et al., 2010; Hawkins et al., 2017). Prescribers commonly use benzodiazepine medications in older adults for prolonged periods beyond the recommended time frames and less frequently consider discontinuation, tapering, or providing psychological support in conjunction with a substitute drug to begin withdrawal (Maust et al., 2016; Paulozzi et al., 2015; Reeve et al., 2017).
In an extensive meta-synthesis of qualitative studies regarding general practitioners' attitudes and experiences of benzodiazepine drug prescribing, clinicians were generally informed about the risks of these drugs and the clinical guidelines for prescribing, but were skeptical about the cautions. They described conflict among wanting to help patients, feeling pressured by patients and third-party payers, and time and resource availability. There was a sense of the “lesser evil” in prescribing benzodiazepine medications over providing psychosocial treatments specific to patients' concerns. Lack of alternative treatments along with providers' perception of the validity or effectiveness of nonpharmacological treatments resulted in taking a path of least resistance in prescribing benzodiazepine agents. Studies also reported that the interpersonal relationship with patients added tension in the prescribing decision, with prescribers not wanting to disrupt the relationship with known patients by not giving them the immediate relief they wanted. Similarly, if patients transferred treatment from another provider who had initiated a benzodiazepine drug prescription, providers did not want to alter that treatment regimen and frequently chose to refill the prescription without question. The authors recommended clinician training in patient negotiations, awareness of treatment options, strategies for gradual withdrawal, and accessibility of nonpharmacological options as ways to improve adherence to practice guidelines (Sirdifield et al., 2013).
Recommendations to Improve Practice
An obvious solution to reducing the benzodiazepine drug epidemic is for prescribers to follow clinical practice guidelines; however, there are no prescribing guidelines proposed in the United States. Practice guidelines exist for treating anxiety, stress, depression, and sleep disorders, but these are not clearly associated with benzodiazepine treatment. The National Guidelines Clearinghouse includes practice guidelines for social anxiety disorder, depression, and substance use disorders (access https://www.guideline.gov), and in the United Kingdom, there are guidelines through the National Institute for Clinical Excellence (access https://www.nice.org.uk). There are, however, several documents that advise caution in prescribing for these disorders through the Veterans Administration/Department of Defense, U.S. Preventive Services Task Force, and Centers for Disease Control and Prevention. Therefore, the prudent clinician must arrive at treatment guidelines through interpretation of the research evidence. The following recommendations to reduce benzodiazepine drug use are derived from studies by several countries, including Australia, Canada, and the United Kingdom (Conn, Shafer, & Cline, 2017; Dollman et al., 2005; Katzman et al., 2014):
- Carefully and thoroughly assess patients in making a diagnosis and identify the specific behaviors and symptoms that are most troublesome. These behaviors guide clinicians in identifying the priority of treatment targets and the best means of addressing them. If a patient is also taking an opioid medication during any point in treatment, concurrent benzodiazepine drug use is contraindicated.
- Explain to patients (and family members as appropriate) the biological and psychological mechanisms of the symptoms to engage patients in treatment. With older patients, especially those with dementia, engage caregivers and family members in this discussion.
- Discuss treatment options in a holistic manner (i.e., include a combination of psychotherapy, cognitive-behavioral therapy [CBT], pharmacology, herbal alternatives, and lifestyle changes) to reduce symptoms. Elicit patients' commitment to total treatment.
- If benzodiazepine medications are offered, clinicians must explain and provide a written statement of the risks, benefits, and limitations to patients. It is reasonable to offer a short-term benzodiazepine medication prescription, with the expectation that the prescription is limited to 4 weeks and a longer-term plan is in place for continuation of treatment. Any longer-term plan should require monthly review before refill, and a taper plan for discontinuation.
- While the patient is taking benzodiazepine drugs, a condition of refills and follow up is that the prescriber check the Prescription Drug Monitoring Program that most states have online to prevent concurrent prescriptions from different prescribers. The patient needs to know that the prescriber will be doing this, especially during the discontinuation process.
- For inpatients and residential treatment centers and skilled nursing facilities, a consultation with pharmacists provides a team approach for careful consideration of dosages, drug interactions, and alternative treatments.
- Depression is often accompanied by anxiety; however, benzodiazepine medications may potentiate anxiety beyond 2 to 4 weeks of use. Therefore, depression is best treated with serotonergic medications with psychotherapy.
- Sleep disturbances alone and in combination with depression need to be treated first with nonpharmacological approaches, such as sleep hygiene and CBT for insomnia. When pharmacological intervention is necessary, it must be time limited to no longer than 4 weeks, tapered, then reinstituted later as needed.
- When a patient presents with a history of long-term benzodiazepine drug treatment, the clinician must have a candid discussion about the consequences and need for discontinuation. Benzodiazepine medication withdrawal needs to be carefully planned, using an established protocol (e.g., Ashton Manual, access https://www.benzo.org.uk/manual) and tailored to the patient's life demands.
Having the difficult talk with patients about their long-term benzodiazepine medication use takes courage and compassion. Individuals may not see the problems the drug use is causing and may not even experience a dependency on the drug, which interferes with the ability to collaborate with the prescriber in the strenuous process of discontinuation. There needs to be a compassionate yet persistent relationship that supports patients in the process that usually entails discomfort, irritability, and discouragement. The end result, however, is that individuals will be able to think clearly, engage in their environment, and develop coping skills that will serve them in daily living. Clinicians need to understand the evidence supporting clinical practice guidelines and improve the collaborative relationship skills necessary to support patients who ask for benzodiazepine medication prescriptions and refills.
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