Benzodiazepines: The Next Wave?

 

 

 

In the February 22, 2018 issue of the New England Journal of Medicine, Dr. Lembke and others wrote a perspective article about benzodiazepines, titled, “Our Other Prescription Drug Problem.”

The authors voiced concerns that amidst all the attention being given to opioid use disorders and opioid overdose deaths, we are ignoring the harms from overprescribed benzodiazepines. They felt it would be a tragedy if the present attention to opioid overuse and misuse led to more people being prescribed benzodiazepines, leading to a growing problem with this type of medication

While I am firmly in the amen corner on this one, I know physicians in my state have not ignored this problem. Since the South has the highest rate of benzodiazepine prescribing per capita of the U.S., [1] the opioid treatment program physicians frequently talk about how to reduce the overabundance of benzodiazepines, and the dangers they present to our patients.

We’ve seen the adverse events from benzodiazepines for more than ten years. The National Institute on Drug Abuse (NIDA) says deaths where benzodiazepines were involved quadrupled from 2002 to 2015. NIDA also says that when benzodiazepines are mixed with opioids, the risk of death increases ten-fold, and that three-fourths of all opioid overdose deaths also involve benzodiazepines. About two years ago, the FDA issued a black box warning about the overdose dangers from combining benzodiazepines with opioids.

As the Lembke article says, the number of people in the U.S. who were prescribed benzodiazepines increased 67% from 1996 to 2013. The quantity prescribed more than tripled over that time, indicating higher dose have been prescribed. In 2012, for every 100 adults in the U.S., 37.6 prescriptions for benzodiazepines were written. That’s an amazing – and scary – statistic.

It’s so bad in my area that Xanax functions as a form of currency. Forget bitcoin; Xanax works just like money. For example, it costs two Xanax 1mg pills to get someone to run you to the grocery store and back, assuming no other stops. That’s the going price. If you want to go to the hardware store too, you’d probably have to throw in another Xanax or clonazepam.

It’s a cultural thing. People feel like after they fill a prescription of Xanax or another benzodiazepine, it’s theirs to use as they wish. They can sell them, barter them, or even take them. People don’t even view this as wrong or illegal.

Most experts feel ordinary benzodiazepines are overused and prescribed for too long. Besides their risk when taken with opioids or other sedating drugs, and they have serious hazards when taken long-term. In a blog entry on September 1, 2014, I described a study published in the British Medical Journal that showed people who used sleeping pills died prematurely at a rate three times higher than controls who did not use sleeping pills, in a dose-related fashion. [2]

Studies show people on benzodiazepines (and other sedatives, like the “z” drugs like Ambien, Lunesta, and Sonata) were more likely to die from cancer and were more likely to have falls. Studies show an increased risk of dementia in patients who take these medications, though we can’t say for sure that it’s causal.

To make matters worse, analogues forms of some benzodiazepines are being made overseas in clandestine drug labs. Some are extremely potent. For example, an analogue of clonazepam is so potent that it needs to be dosed in micrograms rather than milligrams and can be bought online. We don’t know the magnitude of harm that could be caused by such drugs, because they are difficult to detect in urine drug screens.

I cringe when I encounter a patient who says, “I’ve been on my Xanax now for ten years. I can’t do without it.” Prescribing guidelines say these medications were never intended to be used long-term. They can be effective for a period of weeks to months, but daily use over three months isn’t recommended.

Certain providers seem to prescribe them for the flimsiest of reasons. I know this because when I request patient records, I see on a problem list: “Anxiety – continue clonazepam.” There’s no mention of other treatment that have been tried, no notation about any sort of counseling, which is very effective for some anxiety disorders. There’s no specification about the type of anxiety being treated. Sometimes benzodiazepines are used to treat depression, but since benzos are central nervous system depressants, they tend to worse depression. Sometimes benzodiazepines are prescribed for post-traumatic stress disorder, even though we know from VA studies that benzodiazepines tend to make PTSD worse. [3]

Other experts feel their positive aspects are overlooked, and that they are effective at relieving short-term anxiety, and at inducing sleep. As the Lembke article points out, benzodiazepines can be helpful when prescribed for less than one month, and when used intermittently. When used daily and for months, those benefits disappear, and the risks of benzodiazepines increase.

We aren’t the only country struggling with the negative effects of benzodiazepines. Other countries have attempted to mitigate the negative effects by putting prescribing guidelines into place for physicians to follow. As you will note, some of these countries have had guidelines in place for decades.

 

Ireland: https://health.gov.ie/wp-content/uploads/2014/04/Benzodiazepines-Good-Practice-Guidelines.pdf

Australia: https://www.racgp.org.au/your-practice/guidelines/drugs-of-dependence-b/

United Kingdom: https://www.benzo.org.uk/commit.htm

Canada: https://www.benzo.org.uk/hcb/index.htm

Several countries have adopted the guidelines written by the United Kingdom as their guidelines.

Several states and health organizations have taken on the challenge of writing benzodiazepine prescribing guidelines in the U.S.

Like the authors of the Lembke article, I too hope we see a push to use evidence-based data when prescribing benzodiazepines in the U.S.

  1. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6326a2.htm
  2. Weich et al, “Effect of anxiolytic and hypnotic drug prescriptions on mortality hazards: retrospective cohort study,” British Medical Journal, 2014
  3. https://www.ptsd.va.gov/professional/newsletters/research-quarterly/v23n4.pdf
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6 responses to this post.

  1. So if we reduce benzo prescriptions as we have successfully done in opioids we could have a killer benzo ? When goverment try’s to help the black market never fails to be there to pick up the demand but with a more deadly analog. I am not seeing a solution to this epidemic without some harm reduction model.

    This is so scary!

    Reply

  2. Posted by Justin Morton on August 8, 2018 at 5:45 am

    Glad to see this getting attention, but ironically your article bares no mention of the most severe benzo side effect: withdrawal.

    If people only knew the magnitude of hell awaiting them at the end of their alprazolam voyage they would never have gotten so deep into it.

    That said, your coverage of the Macomb County MI jail benzo withdrawal death (murder) is greatly appreciated.

    J.

    Reply

  3. Posted by Scott on August 8, 2018 at 6:06 am

    Sorry in advance for the length of this post, I always get carried away when discussing these topics.

    Australia recently moved Alprazolam from Schedule 4 to Schedule 8.

    Schedule 4 is the normal / run of the mill schedule for prescription medications. In here you’ll find all benzos except Alprazolam and Flunitrazepam.

    Schedule 8 is where highly addictive but medically necessary drugs go. Here you’ll find Alprazolam, Flunitrazepam, Morphine, Oxycodone etc. Flunitrazepam was added because of spiked drink hysteria many years back, not because it’s any more addictive than other benzos.

    Schedule 8 prescriptions are much more tightly controlled. Ongoing scripts (i.e. with repeats), as well as high dose scripts, require authorisation from the health department (note: it might be called something else, basically a body that provides oversight and prescription monitoring).

    Doing this made it nigh on impossible for a Doctor to justify writing Alprazolam scripts when they had the other Schedule 4 benzos at their disposal.

    As you’d expect, the number of prescriptions dropped. So, supply was reduced.

    Reducing supply doesn’t reduce demand (hello failed “war on drugs”), and the black market has gone and filled the niche.

    The problem with the black market is that now people can buy hundreds or thousands of pills/bars at once. Plus, they’re not capped at 2mg per bar now. Some of these bars have reached 10mg each. I imagine some of them also contain newly invented benzos instead of Alprazolam (“research chemicals”).

    It’s a pretty bad situation and definitely not what they had in mind when rescheduling Alprazolam.

    Anyway, I explained all of the above as it illustrates what happens when a drug that’s in the hearts and minds of the public to the extent that benzos are becomes very hard to get legitimately.

    If Valium, Ativan etc. we’re made much harder to get legitimately it won’t fix the problem. In fact, a bigger, badder problem is likely to arise.

    I think an alternative to a “benzo crackdown” is that prior to initiating a course of benzos patients should be given a series of other treatments:
    1. Try out CBT;
    2. Work with a psychologist;
    3. Less addictive medications.

    If these don’t work, introduce benzos and provide decent instructions to the patient as to how to avoid addiction:
    1. Don’t escalate dose with talking to your Doctor;
    2. Don’t mix with alcohol;
    3. Take them, at most, every second or third day.

    This is what I have done for nearly 10 years and I am not addicted, and still use the same dose as I started on.

    The only downside I see to this method is the cost. In Australia I can get the above services for free or almost free. In ‘user pays’ healthcare not everyone will be able to afford this array of treatments. What happens to them? I can’t answer this.

    What I do know is that cracking down on Doctors and patients in an attempt to reduce benzodiazepine use and / or misuse is likely to have tragic consequences.

    This time let’s learn from history rather than repeating it.

    Reply

  4. Posted by Janice Downey, MD on August 8, 2018 at 2:18 pm

    The idea of guidelines is good. Unfortunately, doctors have gone wildly the opposite way and are ripping patients off benzodiazepines who have no substance abuse and no
    other dangerous issues. I believe in being sensible. I think benzos with opiods are
    a death sentence. Long term use without justification is dangerous medical practice.
    Benzos with any alcohol, benzos with older people regarding increased risk for
    dementia, falls, etc.
    I would like to see guidelines.

    Janice L. Downey, MD

    , etc. In other words, there are appropriate uses of benzos, so I would like to see guidelines.

    Reply

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