Benzodiazepine Harms Overlooked, Especially in Older Adults

Norra MacReady

February 22, 2018

As attention remains focused on opioid abuse, another drug epidemic rages outside the spotlight: inappropriate prescription of benzodiazepines.

In an editorial published in the February 22 issue of the New England Journal of Medicine, Anna Lembke, MD, Jennifer Papac, MD, and Keith Humphreys, PhD, from Stanford University School of Medicine in California, point out that from 1996 to 2013, the number of adults who filled a benzodiazepine prescription rose from 8.1 million to 13.5 million, an increase of 67%. During roughly the same time (1999-2015), deaths from benzodiazepine overdose increased from 1135 to 8791.

"Despite this trend, the adverse effects of benzodiazepine overuse, misuse, and addiction continue to go largely unnoticed," they write.

Concurrent opioid use figured in three quarters of the overdoses, "which may explain why, in the context of a widely recognized opioid problem, the harms associated with benzodiazepines have been overlooked," the editorialists state. They cite data showing that coprescription rates nearly doubled between 2001 and 2013, going from 9% to 17%.

Of particular concern is benzodiazepine use among the elderly, who are especially vulnerable to adverse effects, including an increased risk for falls, fractures, motor vehicle accidents, impaired cognition, and dementia. Professional societies in several countries, including the American Geriatrics Society, have issued guidelines recommending against prescribing benzodiazepines to these patients, as has the Choosing Wisely International campaign, which aims to reduce inappropriate and low-value care.

Nevertheless, "[p]rescribing to older adults continues despite decades of evidence documenting safety concerns, effective alternative treatments, and effective methods for tapering even chronic users," Donovan T. Maust, MD, MS, and coauthors wrote in the Journal of the American Geriatric Society in 2016. Other researchers have found that clinicians often are unaware of the dangers these drugs pose to seniors, or believe they have no other therapeutic options.

Now a new observational study of older adults in the United States, Canada, and Australia confirms that, despite a modest decline in benzodiazepine prescriptions in this population, "use remains inappropriately high — particularly in those aged 85 and older — which warrants further attention from clinicians and policy-makers," the authors write.

Jonathan Brett, MBBS, from the Medicines Policy Research Unit at the University of New South Wales in Sydney, Australia, and colleagues published their findings online February 12 in the Journal of the American Geriatric Society.

The authors used prescription claims data from the US Department of Veterans Affairs (VA), the Ontario (Canada) Drug Benefit Program, and the Australian Pharmaceutical Benefits Scheme to analyze annual incident and prevalent benzodiazepine use among people 65 years of age or older between January 2010 and December 2016. The entire cohort included 8,270,000 people.

They observed a significant and linear decline in prevalent benzodiazepine use, defined as people with at least one prescription claim for a benzodiazepine during a given calendar year, in all three countries during the period studied. In the United States, it declined from 9.2% to 7.3%; in Ontario, Canada, it declined from 18.2% to 13.4%; and in Australia, it declined from 20.2% to 16.8%.

Incident use, defined as a new prescription in a given year for someone with no previous history of benzodiazepine use, also declined in the United States, going from 2.6% to 1.7%, and in Ontario, going from 6.0% to 4.4%. In Australia, incident use changed only slightly and nonsignificantly, going from 7.0% to 6.7%.

In all three countries, rates of incident and prevalent use were highest among women, Brett and colleagues write. In Australia and Ontario, prevalent use was highest among patients 85 years of age or older, but "decreased with advancing age in the U.S. VA population."

The observed decreases in prescriptions "are likely to be in response to safety concerns and lack of evidence of effectiveness," the authors write.

Still, despite these "modest changes," and "in spite of consistent messaging about the hazards of using benzodiazepines in this population, the rates of benzodiazepine use in older adults remain high," perhaps related to a tendency by clinicians and patients alike to minimize the risk these drugs pose.

The finding of high use among the oldest patients in Canada and Australia was "particularly troubling," the authors add, because of the greater potential for harm in this age group.

They also express concern that clinicians may be prescribing "Z-drugs," agents such as zopiclone and zolpidem, instead of benzodiazepines, in a mistaken belief that those products are safer.

One way to begin reducing benzodiazepine prevalence might be to limit the conversion of new to chronic use by "explicitly limiting the duration of new prescriptions and not routinely providing repeat prescriptions," the authors suggest. "For people who have been using benzodiazepines for a long time, a discussion about the risks and benefits of continued therapy and attempts to reduce the dose gradually might be the best strategy."

Lembke and colleagues also emphasize the need for discussions about tapering, and note numerous parallels between patterns of benzodiazepine and opioid use: "Despite the many parallels to the opioid epidemic, there has been little discussion in the media or among clinicians, policymakers, and educators about the problem of overprescribing and overuse of benzodiazepines and z-drugs, or about the harm attributable to these drugs and their illicit analogues," they write.

If measures designed to discourage people from using opioids divert them to benzodiazepines instead, "[i]t would be a tragedy," Lembke and colleagues conclude in their editorial. "We believe that the growing infrastructure to address the opioid epidemic should be harnessed to respond to dangerous trends in benzodiazepine overuse, misuse, and addiction as well."

The authors have disclosed no relevant financial relationships.

J Am Geriatr Soc. Published online February 12, 2018. Abstract

N Engl J Med. 2018;378:693-695. Full text

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