1. What is the decision or change (e.g., clinical topic, practice guideline, system design, delivery of care) you are facing or struggling with where a summary of the evidence would be helpful?

The Safe Use of Prescription Benzodiazepines: Toward Development of a Prescription Guideline.

There is no accurate, generally accepted prescription guideline for benzodiazepines (BZDs). These medications are prescribed at about 66 million doctors’ appointments a year in the U.S., according to a report by the U.S. National Center for Health Statistics. A recent study showed that BZD prescribing had nearly doubled from 2003 through 2015 for ambulatory care visits.[1] For every 100 adults that visit an office-based doctor over the course of a year, 27 visits will result in a prescription for a benzodiazepine.[2] Opioid overdose deaths that included BZDs increased an astounding 1082% between 1999 and 2020, and 30% of overdose deaths involve BZD use.[3] The overdose mortality rate involving benzodiazepines for women between the ages of 30 and 64 has increased by 830 percent between 1996 and 2017.[4] Four-fifths of those prescribed BZDs indicate use for more than six months, far beyond the “short-term” use recommendation of the FDA.[5]

See supporting documentation for references.

2. Why are you struggling with this issue?

BZDs have been in use for over 60 years and have long been a favored clinician tool, especially for the treatment of anxiety, insomnia, and seizures. Twenty-two prescription guidelines have been written specifically for BZDs. Another 80-plus guidelines that include BZDs, sometimes also including drugs, have also been written by a variety of organizations in their larger context of addressing certain medical conditions (e.g., anxiety, seizures). Unfortunately, there are many inconsistencies between these guidelines, and none of them cover all aspects of BZD prescription. Most troubling, some of the extant guidelines do not address the problems associated with long-term use. Many of these guidelines recommend standard 4-week tapers for long-term BZ users, regardless of current dosage, duration of use or condition of the patient. This rapid taper can result in harmful symptom s, long-term protracted withdrawal, and suicide. A recent large patient survey (n = 1207) showed that the resultant long-term injury can persist for months to years post-withdrawal.[6]

Only one of these “guidelines” uses GRADE methodology and can be truly termed as a guideline. This guideline[7], despite its more general title, focuses only on deprescribing BZDs that are employed in the treatment of insomnia and recommends a more rapid tapering rate than proposed in other research or by expert opinion.[8,9] In addition, most “guidelines” do not follow FDA label recommendations and are incomplete. There is clearly a need for an evidence-based prescription guideline for BZDs which can be used across the U.S.

Despite the severity of the opioid crisis, which began to receive national attention in the late 1990s, no comprehensive opioid prescription guideline was produced until March 2016, when the Centers for Disease Control and Prevention (CDC) published its CDC Guideline for Prescribing Opioids for Chronic Pain. Since then, the rate of opioid prescription decrease in Ohio emergency rooms quadrupled.[10] Other studies have shown a 13% to 24% reduction in the prescription rate of opioids following the introduction of the CDC guideline.[11,12] To achieve a similar reduction in the rate of long-term prescription of BZDs, an evidence-based BZD prescription guideline will need to be developed by a credible, unbiased source, and promoted to gain adoption.

3. What do you want to see changed? How will you know that your issue is improving or has been addressed?

We are requesting the Agency for Healthcare Research and Quality (AHRQ) to support the development of an evidence report on the safe use of prescription BZDs. This would provide the much-needed foundation for other organizations to develop effective evidence-based prescribing guidelines for BZDs. With AHRQ’s focus on patient safety, it seems congruent with the agency’s mission to help clinicians recognize the appropriate and limited uses of BZDs, and to especially have guidelines that minimize the potentially deleterious effects of long-term BZD use. The need for guidelines is particularly salient given the 2021 FDA boxed warning on BZDs[13] that maintains:
"Benzodiazepines are widely used to treat many conditions, including anxiety, insomnia, and seizures. The current prescribing information for benzodiazepines does not provide adequate warnings about these serious risks and harms associated with these medicines so they may be prescribed and used inappropriately. This increases these serious risks, especially when benzodiazepines are used with some other medicines and substances.
"Benzodiazepines can be an important treatment option for treating disorders for which these drugs are indicated. However, even when taken at recommended dosages, their use can lead to misuse, abuse, and addiction. Abuse and misuse can result in overdose or death, especially when benzodiazepines are combined with other medicines, such as opioid pain relievers, alcohol, or illicit drugs. Physical dependence can occur when benzodiazepines are taken steadily for several days to weeks, even as prescribed. Stopping them abruptly or reducing the dosage too quickly can result in withdrawal reactions, including seizures, which can be life-threatening."

We believe that this request to support the development of an evidence report on BZD safe prescribing is solidly in line with AHRQ’s commitment. This commitment - to help front-line clinicians understand what to do to make patient care safer and how to go about it by implementing evidence-based practices and accelerating and amplifying improvements in quality and safety for patients - is a central tenet of this request.

Note that the Colorado Consortium for Prescription Drug Abuse Prevention, in cooperation with the University of Colorado Anschutz Medical Center, has produced a benzodiazepine prescription guidance document, which collates many of the existing guidelines.[14]

The goal is to produce an evidence report that can be used to develop a unifying prescription guideline for BZDs which has timely, evidence-based information on the proper use of BZDs, the dangers of BZD physiologic dependence and its withdrawal syndrome and the corresponding limitations on duration of prescription. It is desirable for the evidence report to encompass all of the benzodiazepine receptor agonists (BZRAs, which include the Z-drugs).

The evidence report should call for a review of the many extant guidelines. The report should address all phases of prescription, including but not limited to

1. BZD-specific patient engagement guidance.
2. when to avoid the use of BZDs.
3. consideration of treatments that do not involve the use of BZDs.
4. first- and second-line indications for BZD therapy.
5. polypharmacy and duration-of-use considerations.
6. BZD-specific medication dependence guidance, including informing the patient.
7. dosage and duration guidance, and
8. post-prescription follow-up guidance.

There are many paths to the production of such a BZD prescription guideline. It is requested that the evidence report include guidance that the development of a BZD prescription guideline is to be conducted in a manner similar to that used for the development of the CDC’s opioid prescription guideline, specifically including:

• Producing it using GRADE or an equivalent methodology.
• Producing it by experts who are familiar with the requirements of medication guidelines.
• Subjecting it to a series of reviews by a multi-site, multi-disciplinary panel of BZD experts.
• Subjecting it to review by Department of Health and Human Services experts, as determined by AHRQ.

The requested evidence report is the initial step in the development of an overall comprehensive and accurate guideline for prescribing benzodiazepine medications. Clearly the guideline itself needs the most accurate information available, and will take considerable time to develop. The evidence report can be done with less rigor, focusing on the inaccuracies, missing information and discrepancies between the existing “guidelines”, and citing the evidence of the harm of the lack of an accurate guideline.

The best existing model for the amount of time and effort required for the development of a comprehensive guideline for prescribing benzodiazepine medications is arguably the experience with developing the CDC Guideline for Prescribing Opioids for Chronic Pain.

4. When do you need the evidence report?

Fri, 06/30/2023

5. What will you do with the evidence report?

An evidence report on the safe use of prescription benzodiazepines would become the much-needed foundation for the development of a guideline for prescribing benzodiazepine medications. This guideline would become the basis for healthcare decisions surrounding anxiety management and other current uses of BZDs, in the same manner that the corresponding CDC Guideline for Prescribing Opioids for Chronic Pain has become the gold standard for pain management. As with the adoption of the opioid guidelines, it is anticipated that it will take multiple years for a guideline for prescribing benzodiazepine medications to become a generally adopted.

Supporting Documentation

Safe Use of Prescription Benzodiazepines - AHRQ supplemental information (Word, 38 KB)

Optional Information About You

What is your role or perspective? Physician

If you are you making a suggestion on behalf of an organization, please state the name of the organization The Alliance for Benzodiazepine Best Practices

May we contact you if we have questions about your nomination? Yes