Am Fam Physician. 2023;108(3):260-266
Published online August 11, 2023.
Author disclosure: No relevant financial relationships.
In the United States, more than 30 million adults have reported taking a benzodiazepine within the past year. Misuse—use of a drug in a way that a doctor did not direct—accounts for 17.2% of all benzodiazepine use. Family physicians face challenges when balancing the patient's perceived benefits of benzodiazepines with known risks and lack of evidence supporting their use. Benzodiazepines cause significant central nervous system–related adverse effects including sedation, confusion, memory loss, depression, falls, fractures, and motor vehicle crashes. Factors that increase the risk of adverse effects and misuse are other substance use disorders, using concomitant central nervous system medications, and central nervous system or pulmonary diseases. Compared with intermittent use, chronic daily use in older adults is associated with a higher risk of falls, fractures, hospitalizations, and death. Withdrawal symptoms such as anxiety, sleep disturbances, and agitation are common and often prolonged. Adjunctive treatment with antiepileptics, antidepressants, and pregabalin has been shown to lessen withdrawal symptoms. Deprescribing benzodiazepines for patients who use them chronically should be individualized with slow tapering over weeks to months, or longer, to minimize the intensity of withdrawal symptoms. Incorporating behavioral interventions, such as cognitive behavior therapy, improves deprescribing outcomes.
In the United States between 2014 and 2016, nearly one-half (48%) of the estimated 65.9 million office visits per year where benzodiazepines were prescribed were primary care visits, and most were continued prescriptions.1 The rapid anxiolytic and sedative properties of benzodiazepines make them an attractive option for treating acute anxiety and insomnia, but data are lacking to support ongoing therapy for more than one month.2 Therefore, family physicians face challenges when balancing the patient's perceived benefits of benzodiazepines with known risks and lack of evidence supporting their use. Because of their potent agonistic activity on the gamma-aminobutyric acid receptors in the brain and periphery, benzodiazepines cause receptor downregulation within weeks of use.3 Tolerance to anxiolytic and hypnotic effects can develop soon after, with physiologic and psychological dependence. This dependence often leads to continued benzodiazepine use to abate withdrawal.4
| Clinical recommendation | Evidence rating | Comments |
|---|---|---|
| Avoid chronic benzodiazepine use to prevent serious adverse effects including depression, falls, motor vehicle crashes, and cognitive deficits or dementia.16,19–23 | B | Meta-analysis of lower-quality cohort studies |
| Cognitive behavior therapy with gradual tapering may increase the success of deprescribing benzodiazepines compared with tapering alone.31 | B | Randomized controlled trials of limited-quality patient-oriented evidence |
| Consider adjunct pharmacotherapy using tricyclic antidepressants, paroxetine, carbamazepine, or pregabalin (Lyrica) to facilitate benzodiazepine tapering and reduce withdrawal symptoms.35 | B | Meta-analysis of lower-quality randomized controlled trials |
| Recommendation | Sponsoring organization |
|---|---|
| Do not use benzodiazepines or other sedative-hypnotics in older adults as first-choice treatment for insomnia, agitation, or delirium. | American Geriatrics Society |
| Do not routinely continue sedative hypnotics (e.g., temazepam, zolpidem), diphenhydramine, benzodiazepines, or serotonin modulators (e.g., trazodone) for long-term treatment of insomnia in geriatric populations. Consider the use of cognitive behavior therapy as an alternative. | Society for Post-Acute and Long-Term Care Medicine |
| Do not combine opioids with benzodiazepines or gabapentinoids to treat pain in older adults; reevaluate routinely for deprescribing during chronic use. | American Society of Consultant Pharmacists |
| Do not use three or more central nervous system–active medications (e.g., antidepressants, benzodiazepines, z-drugs [i.e., zopiclone, eszopiclone, and zaleplon], opioids, gabapentinoids, antipsychotics, antiepileptics), especially in older adults. | American Society of Consultant Pharmacists |
Identifying and diagnosing benzodiazepine use disorder can be challenging. In 2013, the Diagnostic and Statistical Manual of Mental Disorders, 5th ed., (DSM-5) combined the individual diagnoses of substance abuse and substance dependence into a single diagnosis of substance use disorder. Substance use disorders are defined by pathologic behaviors that cause an individual to continue to use a substance despite experiencing significant problems related to that substance. The DSM-5, text revision categorizes benzodiazepine use disorder as a subtype of the broader category of sedative, hypnotic, or anxiolytic use disorder, but this article will focus only on the benzodiazepine subtype.
The diagnosis of benzodiazepine use disorder is made using 11 criteria that fall into broad categories of impaired control, social impairment, hazardous use, and pharmacologic effects (Table 1).5 The disorder can be further classified by severity depending on the number of criteria met, with only two criteria required for a diagnosis of mild benzodiazepine use disorder.5 Although the behaviors that characterize misuse—use of a drug in a way that a doctor did not direct—are sometimes associated with benzodiazepine use disorder, some (e.g., diversion, nonmedical use, use without a prescription) do not strictly fall within the diagnostic criteria for the disorder. Nevertheless, the potential for misuse of benzodiazepines should be considered by prescribing physicians. The 2015–2016 National Survey on Drug Use and Health showed that 12.6% of the U.S. population (30.6 million people) had used benzodiazepines in the past year, and misuse accounted for 17.2% of use overall. Nearly 7 in 10 people who reported misuse obtained benzodiazepines from a friend or relative. Adults 18 to 25 years of age have the highest rate of misuse compared with older adults.6
Note: This criterion is not considered to be met for individuals taking sedatives, hypnotics, or anxiolytics under medical supervision. Specify current severity: Mild: Presence of 2–3 symptoms Moderate: Presence of 4–5 symptoms Severe: Presence of 6 or more symptoms |
What Are the Risk Factors for Benzodiazepine Misuse and Long-term Use?
An existing or past substance use disorder is the largest risk factor for benzodiazepine misuse. Younger age, chronic sleep disorders, and chronic illness are also associated with benzodiazepine misuse.7,8 Long-term (more than 12 consecutive weeks) benzodiazepine use is more likely in older individuals and those with comorbid conditions.9
EVIDENCE SUMMARY
Substance use disorder is the most significant risk factor for benzodiazepine misuse; 69.5% of those with opioid use disorder, 27.1% with alcohol use disorder, and 77.7% with combined opioid and alcohol use disorder admit to misusing benzodiazepines in their lifetimes.10 Misuse of or dependence on any of these substances, plus using prescription opioids or stimulants, increases the risk even further.7,8,11–14
Many demographic characteristics have been studied to determine the likelihood of benzodiazepine misuse and long-term use (Table 27–14). Lifestyle factors associated with chronic benzodiazepine use, defined as prescriptions for two or more consecutive years without pause, include smoking (odds ratio [OR] = 1.8; 95% CI, 1.6 to 2.1), alcohol use (OR = 1.5; 95% CI, 1.2 to 2.0), and sleep difficulties (OR = 1.4; 95% CI, 1.4 to 1.5), whereas exercise seemed to protect against chronic use (OR = 0.9; 95% CI, 0.88 to 0.96).15
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