Prescriptions for benzodiazepines with opioid analgesics may lead to medication-related deaths

Prescriptions for benzodiazepines are rising in primary care, and their frequent combined use with opioid analgesics may be contributing to medication-related deaths, a finding that goes largely unreported, according to Stanford researchers.

Results presented today in a scientific poster at the American Academy of Pain Medicine's 30th Annual Meeting highlighted the trend in benzodiazepine prescriptions between 2002 and 2009. Examining a nationally representative sample, the team from Stanford University and Stanford Hospital and Clinics, in Palo Alto, Calif., found that primary care providers are prescribing benzodiazepine medication, used primarily to treat anxiety, mood disorders and insomnia, at greater rates than ever before and frequently combining them with opioid prescriptions.

This alarming trend comes as recent government and media reports highlight rising deaths related to prescription drugs, in particular opioid analgesics (Jones et al, JAMA 2013;309:657-9; Warner et al, NCHS Data Brief 2009;22:1-8). Data have shown that drug combinations of benzodiazepines and opioids contribute to at least 30% of opioid-related deaths (Jones et al, JAMA 2013;309:657-9).

Further concerns arise because of the numerous problems associated with benzodiazepine medications, including emergency department visits, falls in the elderly, and the development of physical and psychological dependence, study authors wrote.

"More research is needed to elucidate the reason behind the increase in benzodiazepine prescription, and a national effort is needed to highlight the danger of co-prescription of benzodiazepines and opioids," said principal investigator Sean Mackey, MD, director of the Stanford Systems Neuroscience and Pain Lab.

Of 3.1 billion primary care visits between 2002 and 2009, represented by the National Ambulatory Medical Center Survey (NAMCS) from the Centers for Disease Control and Prevention, 12.6% involved prescriptions for benzodiazepines or opioids, and prescription of benzodiazepines grew by 12.5% a year.

After controlling for patient demographics, including race, ethnicity, age, gender, and insurance type, patient visits involving opioid prescriptions were 4.2 times more likely to also have simultaneous prescriptions of benzodiazepine. In fact, joint prescriptions of both benzodiazepines and opioids increased by 12% a year.

Study co-author Ming-Chih Kao, PhD, MD, a clinical assistant professor with Stanford University Medical Center, said benzodiazepines are good medications for some people at some times, but cautioned that doses that are well tolerated when taken alone have greater risk for depressing the central nervous system when combined with opioids. Dr. Kao said prescribing small-dose, benzodiazepine medications taken on an as-needed basis has become a common practice and discussed why the risky combination with opioids may have grown more frequent among patients with pain.

"As a complex, emotional experience, pain often is accompanied by significant alterations of mood, in particular anxiety," Dr. Kao said. "Anxiety disorders can be managed with psychological interventions in conjunction with anxiolytic medications."

In addition to the need for better provider education on the cautions of combining these medications, Dr. Kao called for better coordination between prescribers of opioid medications, who are often primary care physicians or pain specialists, with prescribers of benzodiazepines, often primary care physicians or psychiatrists.

Source: Stanford University Medical Center