Two new benzodiazepine studies have been published recently and both reveal concerning (albeit unsurprising to benzodiazepine safety advocates) results:

 

Benzodiazepine Use and Misuse Among Adults in the United States

The first, a study entitled “Benzodiazepine Use and Misuse Among Adults in the United States,” was published in the journal Psychiatric Services. The study’s lead researcher, Dr. Donovan Maust of the University of Michigan’s Department of Psychiatry, and his colleagues analyzed data from the 2015 and 2016 National Survey on Drug Use and Health (NSDUH), an annual nationwide survey funded by the U.S. Substance Abuse and Mental Health Services Administration. The goals of the study were to determine prevalence of benzodiazepine use (both as prescribed and misuse), characterize misuse, and examine variation by age.

In light of long-established benzodiazepine risks and harms, the data revealed by this study is alarming:

1. A total of 30.6 million adults (12.6%) reported benzodiazepine use in the past year—25.3 million (10.4%) as prescribed and 5.3 million (2.2%) misuse. That figure is almost double the between 4-6 percent estimated by studies in 2013 and 2014, although the authors of this study point out that the differences may be due, at least in part, to differing survey methodologies.

2. Misuse—described as “any way a doctor did not direct,” including using the drugs without a prescription, taking higher doses than prescribed, or taking them more often or longer than prescribed—accounted for 17.2% of overall use. Young adults, aged 18-25, were revealed to be most likely to misuse. In response to that figure, Dr. Donovan Maust is quoted as saying, “If you look at younger adults, basically misuse was as common as prescribed use, which obviously is kind of disturbing.” Misuse of benzodiazepines declined with age, Maust and colleagues discovered: 3.3 percent among those aged 26 to 34; 1.7 percent among those aged 35 to 49; 1.4 percent among people aged 50 to 64; and just 0.6 percent among people 65 and older. Misuse and abuse of or dependence on prescription opioids or stimulants were strongly associated with benzodiazepine misuse. Benzodiazepine misuse without a prescription was the most common type of misuse, and a friend or relative was the most common source. Adults ages ≥50 were more likely than younger adults to use a benzodiazepine more often than prescribed and to use a benzodiazepine to help with sleep.

3. While some previous studies have pointed to seniors age 65 and older as the most prevalent users of benzodiazepines, results of this study revealed that adults ages 50-64 had the highest prescribed use (12.9%).

According to several news outlets, including the Chicago Tribune, Dr. Maust offered the following commentary in reference to his study’s findings: “Benzodiazepines are being prescribed far too frequently, given that evidence reviews have shown that benzos are of little to no value in treating anxiety, panic disorders or insomnia. Cognitive behavioral therapy and psychotherapy often outperform benzodiazepines, and the drugs have been shown to actually interfere with the effects of such proven treatments. Benzos for anxiety is like opioids for chronic pain. There’s a small subset of patients with treatment-resistant conditions where use may be appropriate. The current amount of use way, way exceeds what the evidence would support.”

To learn more: Episode 20 of the podcast entitled “Psychiatric Services From Pages to Practice,” which aired on January 15, 2019, features Psychiatric Services Editor Lisa Dixon, M.D., M.P.H. (LD), and Podcast Editor and co-host Josh Berezin, M.D. (JB), M.S. discussing key aspects of this study.

 

Patterns in Outpatient Benzodiazepine Prescribing in the United States

The second, a study entitled “Patterns in Outpatient Benzodiazepine Prescribing in the United States,” was published in the journal JAMA Network Open. Using nationally representative National Ambulatory Medical Care Survey data, Sumit D. Agarwal, M.D., and Bruce E. Landon, M.D., from Harvard Medical School in Boston, quantified patterns in outpatient benzodiazepine prescribing and compared them across specialties and indications. Data on more than 386,000 doctor visits from 2003 through 2015 was analyzed.

The results of this study were also concerning:

1. The percentage of outpatient medical visits that led to a benzodiazepine prescription doubled—increasing from 3.8% to 7.4%—from 2003 to 2015.

2. The prescribing rate amongst psychiatrists remained unchanged at about 30% of visits. Otherwise, the prescribing rate increased among all other physicians—the rate among primary care doctors more than doubling, increasing from 3.6% to 7.5% of visits. In other words, visits to primary care physicians accounted for approximately half of all benzodiazepine visits.

3. The benzodiazepine visit rate increased by 6.9% for anxiety and depression; by 1.9% for neurologic conditions; by 4.9% for back and/or chronic pain (both non-FDA-approved indications); and by 2.6% for other conditions. Use did not change for the indication of insomnia.

4. The rate of co-prescribing benzodiazepines with opiates quadrupled from 0.5% in 2003 to 2% in 2015. (Note: In 2016, the FDA issued its strongest warning about serious risks and death when combining opioid pain or cough medicines with benzodiazepines. Only time, in addition to further analyzation of data beyond 2015, will tell if warnings have been heeded).

5. The co-prescribing rate of benzodiazepines with other sedating medications increased from 0.7 to 1.5%.

 

Notes: Shaded areas on left graph indicate confidence intervals.
Source: Sumit Agarwal, Brigham and Women’s Hospital
Credit: Koko Nakajima/NPR

“Surprisingly few guidelines exist for a medication that is prescribed by so many different types of physicians and for so many different indications,” the study authors conclude. The researchers also say that benzodiazepine-related overdose deaths have significantly increased from 0.6 per 100,000 adults in 1999 to 4.4 in 2016. “In light of increasing death rates related to benzodiazepine overdose, addressing prescribing patterns may help curb the growing use of benzodiazepines,” they state.

According to Medscape Medical News, Dr. Agarwal offered the following commentary in reference to the study’s results: “The pendulum has begun to swing in how we prescribe opioids, but we really need to be cautious in how we prescribe benzodiazepines too. Benzodiazepines are easy to start but hard to stop. I’m surprised that we’re not talking about this more. This has been called our ‘other’ prescription drug problem.”

To learn more: This study was covered by various outlets including Medscape, The Hill, MPR, NPR, and MedShadow. It’s important to note, however, that the language in some of these articles fails to make the very critical distinction between addiction (or the term “addictive”) and prescribed physical dependence.