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Opioids Still Overprescribed to Patients Taking Benzodiazepines

April 19, 2018

By Marilynn Larkin

NEW YORK—Although rates of new opioid prescriptions for patients on benzodiazepines have decreased in recent years, they remain higher than rates in the general population, researchers say.

"Benzodiazepines are widely used by patients and most of them probably do not realize how easy it is to accidentally overdose when they are also prescribed an opioid," Dr. Joseph Ladapo of the University of California, Los Angeles, told Reuters Health.

"I have taken care of patients who have been admitted to the hospital for exactly this reason," he said by email, "and none of them seemed to know how risky it was to be concurrently using both benzodiazepines and opioids."

And although clinicians are aware of the overdose risks associated with this combination, he said, "as a population, we probably under-recognize it."

Dr. Ladapo and colleagues analyzed data from 2005 to 2015 on adults 20 years or older who received a new opioid prescription while concurrently taking a benzodiazepine.

As reported online April 11 in JAMA Psychiatry and at the 2018 Society of General Internal Medicine Annual Meeting in Denver, the annual number of adults with a new opioid prescription who reported using benzodiazepines during the study period rose from 7.3 million to 13.0 million, while the number of those who reported not using benzodiazepines rose from 202.8 million to 216.1 million.

Rates of new opioid prescriptions among adults using a benzodiazepine increased significantly from 189 to 351 per 1,000 persons between 2005 and 2010 and decreased significantly to 172 per 1,000 persons by 2015.

By contrast, new opioid prescriptions in the general population not using benzodiazepines increased nonsignificantly from 78 to 93 per 1,000 persons between 2005 and 2010 and decreased nonsignificantly to 79 per 1,000 persons by 2015.

After adjustment for demographic characteristics, comorbidities, and diagnoses associated with pain (e.g., cancer, back pain, headache, musculoskeletal pain, injuries), the likelihood of receiving a new opioid prescription during an ambulatory visit remained higher for patients concurrently using benzodiazepines compared with the general population (adjusted relative risk, 1.83).

Naloxone, which has been recommended by the Surgeon General as an antidote to opioid overdose, was coprescribed in less than 1% of visits when a patient concurrently used a benzodiazepine.

"Physicians should reduce the rates at which they prescribe opioids to patients using sedatives," Dr. Ladapo said. "The 'right' level is not zero but it is lower than what we are currently doing."

"We can say that pretty confidently because we showed that the rates of new prescriptions increased rapidly from 2005-2010 and then fell rapidly from 2010-2015," he noted. "If the prescribing choices were not discretionary, we would not see such large fluctuations."

Dr. Arthur Williams of the Division of Substance Use Disorders at Columbia University Irving Medical Center in New York City commented, "Amid all of the media coverage accusing doctors of loose prescribing, or wrongful advertising by pharma companies, there has been less attention to the fact that patients often know what they want, for better or worse, and press for it."

"A perennial clinical challenge for addiction specialists is the high rate of benzodiazepine use among patients on opioids or in treatment for opioid use disorders," he told Reuters Health by email. "For instance, often more than half of patients in methadone programs use or abuse benzodiazepines."

"In some primary care settings, concomitant benzodiazepine use, or requests for benzodiazepines, is a marker for high-risk patients, in addition to increasing the likelihood of a bad outcome," he said.

"Although there have been theoretical concerns about patients going to the black market for opioids if rates of prescription slow," he said, "the same concerns hold true for benzodiazepines - illicitly obtained benzodiazepines may be forgeries containing multiple adulterants, if not fentanyl, further raising risk of overdose."

"A simplistic guideline to not co-prescribe opioids with benzodiazepines risks abandoning patients in the greatest clinical need," he said.

"A much more effective response would likely include shifting patients with benzodiazepine use from full agonist opioids to partial agonist opioids such as buprenorphine-based pain relievers, which have a much lower risk of respiratory suppression and overdose," Dr. Williams concluded.


JAMA Psychiatry 2018.

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