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Join L. Joseph Parker, a research physician, as we explore a recent comparative effectiveness study that investigates the impact of discontinuing long-term benzodiazepine therapy on patients’ mortality and adverse events, especially when considering their baseline opioid exposure. Discover the key findings, implications, and the potential risks and benefits associated with benzodiazepine discontinuation in patients prescribed for stable long-term treatment.

L. Joseph Parker is a research physician.

He discusses the KevinMD article, “Redefining medical caution: How recent studies challenge benzodiazepine prescription norms.”

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Transcript

Kevin Pho: Hi, and welcome to the show. Subscribe at KevinMD.com/podcast, and get CME for this episode by clicking on the CME link in the show notes. Today we welcome back Joseph Parker. He is a research physician, and we’re going to talk about a recent JAMA Network Open study, “Benzodiazepine discontinuation and mortality among patients receiving long-term benzodiazepine therapy.” Joseph, welcome to the show.

L. Joseph Parker: Thank you very much, Dr. Pho.

Kevin Pho: So Joseph has been on multiple times. Go to KevinMD.com/podcast to hear his story and prior episodes. Today let’s jump right into this JAMA Network Open study. What about it caught your eye?

L. Joseph Parker: Well, it encapsulated something that I had put together over the years from other studies that had not looked directly, or as directly, at this issue.

The question was, when someone comes to you on multiple controlled medications, and specifically for this study opiates and benzodiazepines, should you discontinue them because of the risk of using a combination of these medications, or should you not? Where does the evidence lie? We know there’s dangers in both directions.

Kevin Pho: OK, so what did this study look at, and what did it find?

L. Joseph Parker: So this study had evaluated patients who were on opiates, and had tracked those who were discontinued compared to those who were not, to see which group would have the better success over the long term.

And within the first 90 days they run pretty much parallel. There’s actually a slightly higher rate on the graph in death with those continued. But after 90 days there is a dramatic increase in the number of deaths in those patients who were discontinued on the benzodiazepines. Which would surprise a lot of people, because you would think the immediate danger of discontinuing benzodiazepines would be in the first 90 days, since benzodiazepine withdrawal is extremely dangerous.

But that’s not what the study shows. The study shows that there’s actually a 1.6 times higher rate of death in those discontinued on their benzodiazepines than in those continued on them.

Kevin Pho: As a physician, you have had experience with controlled substances, opiates and benzodiazepines. Can you speculate as to some of the reasons that could explain some of these findings?

L. Joseph Parker: Sure. Patients end up on benzodiazepines and opiates for multiple reasons. Quite often, whatever event caused their disability and severe chronic pain that put them on opiates in the first place has also caused PTSD. So quite often they will come to you on Xanax for panic attacks. And also they’re likely, if they’ve got a spinal injury, to have spasticity and muscle spasms, and they might be on diazepam for that. And those are the two most commonly used. You will also see lorazepam used for that latter purpose.

So I’ve had patients come to me on two benzodiazepines as well as their opiates. My record was three opiates and two benzodiazepines at the same time, from another physician.

So they come to you on these and you have to decide, do I continue these? Because of course there’s a dramatic danger right now in the law enforcement perception that if you prescribe combined medications you’re somehow breaking the law, even if they come to you on them.

Kevin Pho: And according to the study, if you do discontinue those benzodiazepines, they’re going to have a higher mortality rate after a certain period of time. Is that correct?

L. Joseph Parker: That’s correct. And I would like to see further studies to quantify the cause of that.

So there are multiple things that could lead to this. You’re past the 90-day window, so it should not be seizures from abrupt withdrawal. So now we’re looking at, does the stress of the untreated anxiety increase their likelihood of death from stroke and heart attacks, which of course is hypertension related and or just cardiac related, because stress hormones are toxic to the body in many ways?

And the other question would be, do these people lose their will to live, and do they take themselves out of the equation? Does the suicide rate go up when you take people off benzodiazepines?

And that leads back to a previous study called BIND, that was the benzodiazepine induced neurological dysfunction study, which showed that placing patients on long-term benzodiazepines causes some fundamental changes in their neuropsychological functioning, that predisposes them to problems if you keep them on it long term, and problems if you take them off of it after they’ve been on it long term. And no one was sure which factor outweighed the other.

I can tell you right now that I’ve looked at over a hundred physician prosecutions, and in at least half of them you will see the government used the phrase, the charged physician used dangerous medications in dangerous combinations. And they’re almost always talking about opiates and benzodiazepines. And they seem to be of the thinking that these medications cannot be used together, or should not be used together, simply because studies have come out saying that you should use extreme caution when prescribing these together.

Kevin Pho: So it sounds like data like this puts physicians in a very difficult situation, right? Because the scenario that you mentioned earlier, a patient may come to you already on multiple controlled substances, and you worry about the detrimental effects of being on these medications versus a study like this, which shows that discontinuing it actually increases mortality. So talk to us about how a physician can unpack the data on both sides and provide perhaps some guidance in terms of what they can do in these particular scenarios.

L. Joseph Parker: This puts us back to the fundamental problem of being a physician in the United States today. No deference is given to your expert opinion by the federal government on what should or should not be done with a specific patient. So the most complicated patients are going to have the most complicated outcomes, and quite often those are unhappy.

So a physician’s first obligation is to their oath and to humanity, and to do no harm. So if someone comes to you already on these medications and you discontinue them, that’s a positive step, you are taking away something they’re already on. But those prescriptions were being written by another doctor, so you are not obligated legally to continue them. Though of course if a patient dies, the family can sue you and the medical board could have some questions.

So that leaves you in an impossible situation, where you must choose between doing what you now know, but before strongly suspected, was very dangerous for the patient. Which would be assuming that every doctor who saw this patient before you didn’t know what they were doing, and on your first visit you’re going to choose to discontinue these medications, despite them having seen experts and other medical health professionals in the past.

So you’re going to make that decision, and that’s the safe thing to do legally if you’re worried about prosecution, because they will not prosecute you for your patient dying as long as you didn’t prescribe something. Or you write that first prescription, and if they come to you on say three opiates and two benzodiazepines and you cut them down to two opiates and one benzodiazepine, you’re still in danger, because that patient could still have an unhappy outcome.

You can do everything right and things can still go wrong. And they can sort through thousands of patient interactions and find that one case that went wrong and throw it up to the public and to a grand jury and later to a jury, as you disregarding the risk of death and addiction from combining these medications.

Kevin Pho: Now, is there a middle ground here? Is it really a binary choice between continuing the medications and stopping cold turkey? Is there a middle ground, like it seems, tapering the medications off?

L. Joseph Parker: It seems to be, because they have gone ahead and prosecuted doctors, me specifically, after stopping an opiate. So patient comes to you on three opiates and two benzodiazepines, I cut them down to two opiates and one benzodiazepine, I was still prosecuted for treating that patient, and convicted. Because the jury does not understand, and perhaps I was not artful at describing to them the fact that taking them off a medication is a positive step to a physician, it is something that you are doing, and it’s disregarding the expertise of the physicians who saw them before.

So I will say this. You need to get a second opinion. You need to have them seen by a psychiatrist if they’re being treated for PTSD, and ask them, is this enough? Because I had an in-house nurse practitioner who was psychiatrically trained, and she did not disagree with the treatment. But that’s not enough. If it’s in house, it can be disregarded. You need an outside psychologist or psychiatrist to say, this medication is necessary for this patient’s health.

Until then, I would start a slow taper until I got that verification, and see if the patient can tolerate it. If they tolerate a taper and you can reduce them down a little, without perhaps discontinuing it completely, perhaps you can help them avoid this higher mortality risk while at the same time providing them a little added safety.

So harm reduction is something that American medicine has not fully embraced the way other nations have. But in this case the harm reduction is not just to the patient but also to the physician.

Kevin Pho: We’re talking to Joseph Parker. He’s a research physician. We’re talking about a recent JAMA Network Open study, “Benzodiazepine discontinuation and mortality among patients receiving long-term benzodiazepine therapy.” Joseph, tell us some resources physicians can turn to, because this is, like you said, a very difficult situation. You mentioned things like getting second opinions before making a choice. Any resources physicians can turn to in order to better elucidate what they should do next?

L. Joseph Parker: Yes. I strongly recommend that physicians look at making good contacts with telemedicine companies. Getting your patient seen by a psychiatrist in the area that I had practiced in could take up to six months. By then you either prescribe that medication for six months, or you’ve already tapered them off of it and perhaps they’re going to suffer this increased mortality rate, they’ll be one of those statistics.

So telemedicine has made it extremely convenient to access specialists, and they can be anywhere in your state, and depending on your state they might be outside your state. And hopefully the patient has good insurance that will cover it, and the specialist can come consult and give you an opinion much more rapidly, because the consultation usually has to take place from one health care facility to another.

So you’re contacting these telemedicine groups and you’re finding that specialist. And finding a psychologist who would be excellent at this is a lot easier than finding a psychiatrist. Psychiatry is not as attractive of a field as it used to be, for lots of reasons, and so finding a psychiatrist is extremely difficult. Now, a nurse practitioner that’s psychiatrically trained would be helpful also. But getting that independent second opinion, that these medications are necessary for the health of the patient, can make all the difference.

Kevin Pho: And my final question, Joseph. Tell us your take-home messages to the KevinMD audience.

L. Joseph Parker: I would say that your medical opinion will be given no deference at all. Dr. Ruan, of the famous Supreme Court case, was board certified in seven different specialties. He actually held the record in the United States of America as the most educated and qualified physician to practice in this country, for any reason, but specifically to treat pain. Yet his opinion on what should be done with patients was given no deference in court, and he was convicted. He was convicted.

So no matter how smart you are, no matter how certain you are that you’re doing the right thing, if you don’t get independent backup it can still be disregarded.

Kevin Pho: Joseph, once again, thank you for coming back on the show, sharing your time, insight, and perspective.

L. Joseph Parker: Thank you.