A good model for BZRAs may be found in the progression of the latest in several waves of opioid crises in the United States. Opioids have for centuries been known to be both very useful and very addictive medications. Although benzodiazepine receptor agonists (BZRAs, which includes benzodiazepines and Z-drugs) have only been in use for since 1961 or later, in many ways they have the same profile as the opioids. Much has been written about the current opioid crisis, but here are the key lessons from the opioid experience that we must carry forward to the world of benzodiazepines.
We are hopeful, sometimes naïvely. From the 1990s on, prescribers moved patients to the newer generation of opioids because they had erroneously been convinced that they were not nearly as addictive as the previous generation. Likewise, there was a shift from the barbiturates to benzodiazepines in the 1960s.
You must listen to patients. Very shortly after the current generation of opioids (e.g., oxycodone and oxycontin) began being prescribed, physicians were flooded with ongoing pain complaints and refill requests. The numbers showed a dependence problem; the warning signs were there. The same is true of BZRAs.
Physiological dependence is common and it happens quickly. The labels of opioids warn of the dangers. But a few influential advocates have vigorously advocated that there is little danger of dependence. The same is true of BZRAs (as it has been with tobacco and vaping devices), while the research overwhelmingly supports their short-term use only.
Regulators follow, they don’t lead. Although the opioid crisis began to receive national attention in the late 1990’s, the CDC (Centers for Disease Control and Prevention) did not produce a guideline for opioid prescription until March 2016. The CDC has yet to produce prescription guidelines for benzodiazepines and Z-drugs, and they are still classified as Schedule IV, the safest of regulated drugs. Black box warning of the dangers of opioid-benzodiazepine co-prescription appeared only after the death toll numbers could not be ignored.
Prescription rates drop only when the evidence of harm has been overwhelming for many years. This is particularly true for such “immediately effective” drugs as opioids and BZRAs. After steadily increasing for most of the roughly 19 years since the addiction problems and related deaths of the current opioids were made widely known, their prescription rate has finally started to flatten. The problems of physiological dependence and significant PAWS with BZRAs were widely publicized in the 1970’s, yet their prescription rate continues to set new records.
Patient satisfaction ratings impede the reduction of “addictive” drugs. The introduction of pain as the “fifth vital sign” in 2001 helped fuel the tremendous rise in opioid prescriptions. Likewise, the trend toward patient satisfaction ratings, with their downside to the clinician who restricts prescription of opioids or BZRAs, has also increased the rate of prescription of both classes of drugs.
The Lesson of Fluoroquinolones
Though effective against infection, the fluoroquinolones (FQs) are inhibitors at the GABAA receptor. FQs include many popular drugs such as ciprofloxacin (Cipro®), ofloxacin (Floxin®), norfloxacin (Noroxin®), levofloxacin (Levaquin®), moxifloxacin (Avelox®), and gemifloxacin (Factive®). After years of complaints from patients prescribed FQs and warnings from researchers about the dangers of FQs, basic research finally proved that they can cause potentially irreversible damage. Only then did this become the basis for a black box warning for FQs as a class. The lessons are clear: 1) anecdotal reports to the FDA about medication-associated injury are very important and 2) research prompted by such reports to prove the relationship between a drug and serious adverse effect is required in order to change FDA-approved labeling. If you even suspect your use of benzodiazepines have led to a negative outcome, your report to the FDA has significant value, and along with many other reports may ultimately result in changes that are important to prescribers and patients alike. This process will take a concerted effort by all of us. For guidance on how to make a report to the FDA of a problem with a benzodiazepine or Z-drug, click here. For an in-depth discussion of the heightened dangers of fluoroquinolones to the benzodiazepine-dependent population, click here (note that you will be directed to another website).
