National Data on Benzodiazepine Use, Overdose Deaths Highlight Groups at Risk
Abstract
Whether overdose deaths associated with benzodiazepines can be attributed to the medications themselves is unclear, but at least one expert says trends in their use by older adults is concerning.
The rate of overdose deaths associated with the use of benzodiazepines rose substantially between 1996 and 2013, according to a report in the American Journal of Public Health.
Grayson Norquist, M.D.: “Older adults … are more sensitive to the effects of [benzodiazepines] and their potential for other comorbid medical problems. We worry about cognitive impairment and associated fall-related injuries,” he said.
Overall, the mortality rate plateaued in recent years, and experts who reviewed the report for Psychiatric News cautioned that the findings are associative, not causal—there is no way to determine if the overdose mortality is related to factors other than benzodiazepine use, including concomitant use of other medications.
But a close analysis of the numbers in the report do point to a trend that may potentially be cause for concern: a steep increase in the dosage and number of benzodiazepine prescriptions filled for individuals aged 44 to 65, and a slow but steady increase in overdose mortality for individuals over 65.
“Physicians need to pay more attention to the use of benzodiazepines in the older populations and ensure they are being used appropriately,” Grayson Norquist, M.D., M.S.P.H, chair of APA’s Council on Quality Care, told Psychiatric News. Norquist is a geriatric psychiatrist and professor of psychiatry at Emory University.
In the study, Marcus Bachhuber, M.D., M.S.H.P., an assistant professor of medicine at Montefiore Medical Center/Albert Einstein College of Medicine, and colleagues examined data from the Medical Expenditure Panel Survey (MEPS) and multiple cause-of-death data from the Centers for Disease Control and Prevention.
They found that between 1996 and 2013, the number of adults filling a benzodiazepine prescription increased 67 percent, from 8.1 million to 13.5 million. Among those filling benzodiazepine prescriptions, the median cumulative quantity filled over the year increased by 140 percent, from 86.8 mg to 208.0 mg lorazepam equivalents. Meanwhile, the rate of overdose fatalities involving benzodiazepines rose more than fivefold from 0.58 to 3.07 per 100,000 adults, with a plateau seen after 2010.
Bachhuber and colleagues acknowledged that the association with mortality may be multi-factorial. “Among people who filled benzodiazepine prescriptions, the median quantity filled over the year more than doubled between 1996 and 2013, suggesting either a higher daily dose or more days of treatment, which potentially increased the risk of fatal overdose,” they wrote. “Second, people at high risk for fatal overdose may be obtaining diverted benzodiazepines. … Finally, increases in alcohol use or combining benzodiazepines with other medications (such as opioid analgesics) could increase the risk of fatal overdose and explain this rise.”
Norquist and other experts who spoke with Psychiatric News emphasized that it is not possible on the basis of the MEPS data to causally link benzodiazepine prescribing to overdose deaths.
“The new report documents a recent marked increase in drug-related overdose deaths in which benzodiazepines were involved,” said Mark Olfson, M.D., M.P.H., a professor of psychiatry at Columbia University Medical Center. “The increase in overdose deaths occurred over a period when there was a considerably more modest increase in benzodiazepine prescriptions. Without more detailed analyses, it would be premature to conclude that the change in benzodiazepine prescribing meaningfully contributed to the increase in overdose deaths.”
Olfson noted that some trends revealed in the data actually point away from benzodiazepines as the causative factor in overdose mortality. For instance, the volume of benzodiazepine prescribing tended to rise faster in males than females and in younger adults than middle-aged adults, while the overdose deaths involving benzodiazepines increased faster among females and middle-aged adults.
“Moving forward, it will be important to evaluate what fraction of the benzodiazepine-related overdose deaths also involves opioids,” he said.
Richard Balon, M.D., a professor of psychiatry at Wayne State University, agreed. “The study documents a rise in overdose deaths that plateaued after 2010, but the way the data are coded in MEPS, they capture all overdoses associated with benzodiazepine use. We don’t know if the deaths are from benzodiazepines or other factors.”
Overdose Deaths Rates Vary Across Age Groups
Comparing benzodiazepine prescribing, use, and overdose deaths across age groups is revealing. The study found that for adults aged 18 to 44, the annual percent change in overdose deaths associated with benzodiazepine use fell, from 15.6 percent from 1999 to 2009 to -2.1 percent from 2010 to 2013. Overdose mortality rates also fell in adults aged 45 to 64: the annual percent change from 1999 to 2008 was 17.2 percent and from 2009 to 2013 it was 5.3 percent.
While the mortality rate from overdose was lowest for adults aged 65 or older (in 2013, it was 0.70 per 100,000 adults compared with 3.2 for those 18 to 44 and 4.2 for those 45 to 65), the age group experienced a steady increase in overdose mortality involving benzodiazepines over the period examined. Additionally, the study found that a higher percent of those 65 or older filled a benzodiazepine prescription throughout the study period compared with younger age groups.
Norquist noted that such trends involving older individuals should be a red flag to clinicians.
“Older adults … are more sensitive to the effects of these medications and their potential for other comorbid medical problems,” he said. “We worry about cognitive impairment and associated fall-related injuries,” he said.
“It’s also concerning that the group that is seeing the largest increases over time [in prescriptions and dosage] is the group that is aged 45 to 64; they will soon be ‘aging’ into the older category and thus could be at even more risk for mortality as they age.”
Are Clinicians Overprescribing Benzodiazepines?
Norquist said that he believes benzodiazepines may be overprescribed, especially in primary care practices where patients may not receive follow-up and monitoring and where the medications may be prescribed for other indications, such as insomnia.
In 2013, the most common indications for benzodiazepine prescription were anxiety disorders (56.1 percent), mood disorders (12.1 percent), and codes in the unclassified category, which include codes for insomnia (12 percent).
Balon said that he believes benzodiazepines have gotten “an unfair rap” and emphasized that it is how they are prescribed that matters. “I have patients who have been on a stable dose of benzodiazepines for a long time,” he said. “But it depends on how you practice—whether you see the patient regularly and whether they are prescribed for the proper diagnosis.”
(An APA practice guideline for panic disorder, approved in 2008 and published in 2009, references use of benzodiazepines for panic disorder and possible adverse effects, including cognitive impairment, risks of falls in geriatric patients, and the risk of misuse by patients with substance use disorder.)
“The key issue is that physicians need to use benzodiazepine as well as any other psychiatric medication only when there is a clear clinical indication for the medication and to monitor its use and side effects on a regular basis,” Norquist said. ■
“Increasing Benzodiazepine Prescriptions and Overdose Mortality in the United States, 1996–2013” can be accessed here.
