Black Box Warning

black coffin

 

 

Last month the FDA (Food and Drug Administration) announced their decision to require black box warnings on opioid and benzodiazepine prescribing information. This warning will state that co-prescribing these two classes of medications increases the risks to patients of death, coma, sleepiness, and respiratory depression. The FDA also said they would require medication guides for patients, describing these risks.

Black box warnings are the strongest warnings issued by the FDA. These warnings are literally placed in a bold black box at the top of the prescribing, where the information is most noticeable.

I applaud the FDA’s action. I think FDA’s statement will make physicians and other providers think twice before blithely writing a benzodiazepine prescription for a patient already prescribed opioids. A black box means, “Take this seriously!”

Ten years ago, co-prescribing of opioids and benzodiazepines was commonplace for primary care physicians in my area. Earlier this year, our state medical board announced they would investigate the top prescribers of opioids and benzodiazepines together. Since then, I have noticed some prescribers appear to be backing away from the routine prescribing of benzodiazepines..

Most opioid treatment centers have policies in place to address benzodiazepine use, both licit and illicit. There are still a few OTPs who approve benzodiazepines to be prescribed for methadone or buprenorphine patients, but I think they are in the minority. Most opioid treatment program physicians feel that besides the dangers of sedation and overdose, there are few medical indications for long-term (more than three months) benzodiazepine prescriptions, and much better long-term treatments for anxiety disorders.

An article In the April 16th, 2016 issue of the American Journal of Public Health underlined how important it is to evaluate benzodiazepine prescribing in the U.S., particularly when prescribed along with opioids. [1]

The authors begin the article by stating that benzodiazepines were found to be involved in nearly a third of opioid overdose deaths in 2013. The authors wished to investigate nation trends in benzodiazepine prescribing and in fatal overdoses involving benzodiazepines.

The authors found the percentage of U.S. adults filling benzodiazepine prescriptions increased significantly over past years. They also found that among people who filled benzodiazepine prescriptions, the amount, defined as lorazepam equivalent doses, also increased significantly. Simultaneously, overdose deaths rates involving benzodiazepines rose nearly four-fold, though deaths appear to have plateaued since 2010.

Another study, this time in Canada, evaluated the risk of death in polysubstance users. In a prospective cohort study of IV drug users, done from 1996 through 2013, benzodiazepine use was more strongly associated with death than any other substance of abuse. [2

Many patients ask why they can’t take benzodiazepines while on methadone or buprenorphine. I tell them I’m mainly worried about the increased risk for overdose death, but I also tell them benzodiazepines are over-prescribed. Prescribing information suggests benzodiazepines are most beneficial when prescribed for no more than three or four weeks. Long-term prescribing of benzodiazepines is generally discouraged, due to serious side effects seen even in patients with no substance use disorders.

Benzodiazepines are associated with increased risk of auto accidents, increased risk of completed suicide, worsening of mood disorders like depression, increased risk of drug-induced dementia, and increased risk of daytime fatigue. Benzodiazepines are also associated with increased risk of cancer, falls, and pneumonia.

Although an association of benzodiazepines with these conditions doesn’t necessarily mean benzodiazepines cause these conditions, it’s a good reason to be conservative when prescribing benzodiazepines and other sedatives, pending further studies.

Sedative medications including benzos can make undiagnosed sleep apnea worse, even to the point of causing death. Obesity increases the risk of sleep apnea, and with more adults becoming obese, the risks of benzodiazepines in such patients may be overlooked.

As for my patients, many of whom are prescribed methadone or buprenorphine, the risk of drug interaction and overdose with the hypnotics usually outweighs all of the benefits, and I recommend that patients do not mix these two types of medications.

  1. Bachhuber et. al., “Increasing Benzodiazepine Prescription and Overdose Mortality in the Unites States, 1996-2013,” American Journal of Public Health, April 16, 2016.
  2. Walton et. al., “The Impact of Benzodiazepine Use on Mortality Among Polysubstance Users in Vancouver, Canada,” Public Health Rep., 2016 May-June;13(3)491-9.
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6 responses to this post.

  1. Posted by Rachel Picard on September 25, 2016 at 3:00 pm

    This is great!

    Sent from my iPhone

    >

    Reply

  2. What would you recommend as a good drug to treat PTSD, and General Anxiety Disorder that WON’T cause QT prolongation or block uptake of potassium?

    Reply

    • Much of the choice of medication would depend on other medical conditions, of course, but first-line treatments for PTSD are SSRIs such as fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil). Some patients do get prolonged QT intervals with these medications, but others do not. It’s probably prudent to monitor the patient’s QT interval. Mirtazepine (Remeron) has also been shown to work on PTSD, with no QT interval concerns that I can find. Effexor works, but again you would need to monitor QT.
      Topiramate in some studies appears to help PTSD, and there’s also evidence for using prazosin.
      Non-medication treatments are evidence-based as well. Most commonly recommended are exposure-based therapy, which involves re-living the trauma, and CPT, or cognitive processing therapy. EMDR (eye movement desensitization reprocessing) has been used successfully to treat PTSD
      You can read more at the VA website and read their evidence-based practice guidelines: http://www.healthquality.va.gov/guidelines/MH/ptsd/
      Benzodiazepines are not recommended for patients with PTSD, as they are associated with poorer outcomes.

      Reply

      • Not all people. And it is never just PTSD. I have co-other stuff too. Please take your reccommendations and shove them where the sun don’t shine because it doesn’t work like that for everyone. Take it from someone who has PTSD and none of that helped me. Right now I rather die, than keep being told the same restrictions that don’t help over and over. I am so tired of everyone should have the same treatment and if you or the government decides that something is apparently killing other ppl might save one. And has no one taken into consideration WhY these ppl are dying! My fiends have died too, guess why..can’t find help..because of “recommendations” that don’t work. How long did it take for people to wake up and see abstinence is probably killing more people than from being on a medication. Tolerance is the deal. You think after 3 weeks of suboxone or now these injections are going to cure someone. If they had not stopped taking their suboxone like “suggested” they would still be alive. Always check your sources..statistics lie!

  3. Posted by jimmy_luv on October 9, 2016 at 6:54 pm

    over 30 years of involvement in drugs (the last 5 have been clean, im 40) the majority of drug-related deaths that have occurred in my locale (Jacksonville/St. Augustine FL) almost always involve benzos and methadone….

    i literally have ~35 friends that have died from overdoses in the last 25 years, and 75% of them involved benzos and opiates… specifically methadone and xanax. oxycodone and xanax seems to be the fav, but the new fentanyl analogs are causing problems, as the fent analogs are so depressive to the breathing…

    i am as hard as they come when talking about addicts. i have ruined my life and spent over $500K on heroin over the years and everything was done in excess, (not proud and not a lie), but i will never mess with methadone and any benzo.

    walked in or woken up to too many people with blue lips, stiff limbs and cold skin to ever want to try playing with that combo.

    people get this idea that if you can do it once, you should be fine. it only kills the weak ones, the n00bs, they got bad dope, etc etc. dont think you can master the combo of opiates/opioids and benzos. i promise youll loose.

    and to anyone thinking that diclazepam or etizolam or any of the other thienodiazepines just because they are not technically a “benzo”, dont do it! its all the same. the entire class of drugs should be avoided period! methadone and etizys will kill you all the same.

    Reply

  4. Please answer this. I have SEVERE dehabilitating anxiety. I am in treatment for my PTSD. Everyday I feel like a giant ball of anxiety even though I take buprenorphine. Everyone is so afraid of Benzos.. that I can’t get any relief. I’ve tried gabapentin, and all the “other” methods of prescriptions besides benzos. Actually muscle relaxers work better for me. I do take .5 mg of clonazepam or 1.5 a day .5 x 3. I have been getting worse. I have been on the same medications for years.. and I have been getting worse, my anxiety worse. Please keep in mind my situation is not simple, I also live with my marriage partner who is severely abusive but not physically. And I have 2 sons with him. No I can’t just leave. No I am not filing for disability. I whiffle waffling for different reasons. I am so tired of constantly running short on my pills because they aren’t enough. I’ve offered to go down on my bupe too. No dice. I fought for 3 years to get on benzos..trying everything from breathing techniques, hypnotizing, other meds.. unfortunately in my weird case they don’t work. Now I get anxiet and have panic attacks every time I see my dr. Because it is always the same. No I can’t be on more, no I can’t have muscle relaxers instead because the government says I will die. Well guys I’m still alive and guess what.. in order to put me out for surgery.. I have been given enough benzos for an elephant and survived just fine. I am not even an addict, it is a by product of abuse and how I chose to deal with it. Just today pharmacy refused to fill my prescription because my dr, instead of writing for 2 weeks..wrote for a month. I always get 2 scripts so I don’t take to many, 2 weeks bupe and clonazepam and 2 weeks bupe and clonazepam. So my dr screwed up and I screwed up.. but now.. I get nothing for 8 days.even though I have a legitimate script. Called my doc and he tells me. Nope cant give anymore, because of government crack down. That’s what I hear everytime I try to ask for help in different doses. I am so done…with this merry go round. I don’t even want to go anymore, just give up on all meds..don’t care about stupid withdrawals anymore. I can’t have any relief because the government and ppl like you who tell everyone that if you mix the two, you will die. How bout I just die anyways and go back to heroin, it’s cheaper, easier to get.. and I don’t have to go through this stupid pill disaster. Do you know how I get treated everytime I have to go to a dentist or regular doctor.. even pharmacies. I’m so tired of it. I have had freakin dr horror story after horror story as well as pharmacies. I will never go to any Walgreens or box store ever again. I special pick independent small pharmacies and they are rare. I see my future as the government and people will meddle so much that in a couple years I won’t be able to get any meds at all. See if you are sick.. hospitals won’t help, if you try to get in to another dr.. nope..full or I’d have to literally go back through drug treatment after being clean for over 9 yrs and already had countless stupid drug counciling..which again was never my prob. Only last year dr figured out oh.. yeah it is the abuse that is a problem, and there is no gov program I can run to. There is no one to magically pick me and my kids out of this situation. Abusive family too. So.. yeah I feel like screw this right now. I want people to know there are so many other people suffering from posts or Suggestions like these!! God Hello Not EVERYONE IS THE SAME!

    Reply

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