CATR: To begin, tell us about the research and clinical work you do.
Dr. Morford: I am an assistant professor at the Yale School of Medicine in the Program of Addiction Medicine. I trained as a general internist, and I see patients primarily at a large opioid treatment program and in an inpatient setting on an addiction consult service. I’m involved in a number of addiction-focused research and educational activities, and I teach trainees in various levels in nursing, physician associate, and medical schools.

CATR: You’ve done research on benzodiazepine use, and I imagine it comes up often clinically for you, too. How prevalent is benzodiazepine use?
Dr. Morford: According to the National Survey on Drug Use and Health, about 12.5% of US adults have used benzodiazepines for prescription and non-medical use in the past year (Maust DT et al, Psychiatric Services 2019;70(2):97–106). If we’re looking at prescribed benzodiazepines, we’ve seen an increase over the past decade or two. One study of data from the National Ambulatory Medical Care Survey showed that in 2003, 3.8% of ambulatory visits involved benzodiazepine prescriptions in the US, and that increased to 7.4% in 2015 (Agarwal SD and Landon BE, JAMA Network Open 2019;2(1):e187399). So, we are seeing increased prescribing of benzodiazepines. In terms of misuse, it’s estimated that a little over 2% of the US population reports misusing benzodiazepines.

CATR: While the story of increases in opioid prescribing has been told, increased use of benzodiazepines is less well characterized. What are your thoughts?
Dr. Morford: I don’t think it’s as well understood as what we saw with opioid prescribing and the role of the pharmaceutical industry in that. What we do know is that the percentage of benzodiazepine prescriptions by psychiatrists has remained relatively stable at around 30% over that time period I talked about from 2003 to 2015, while prescriptions of benzodiazepines by several other physician groups increased. And that includes primary care physicians, who account for more than 50% of all benzodiazepine prescriptions (Agarwal and Landon, 2019).

CATR: Many patients have been prescribed benzodiazepines for years. How should we approach them?
Dr. Morford: For patients who come into my clinic who’ve already been receiving benzodiazepines for a number of years, my first step is to determine the indication and clarify the diagnosis that they were prescribed for. Typically, we will see that benzodiazepines were prescribed for anxiety and for insomnia, without evidence of ongoing or recent use of first-line medication treatments for these disorders.

CATR: And the next step?
Dr. Morford: You’ll want to ask about side effects; this can be educational for patients. Ask your patient if they have experienced sedation, dizziness, and/or falls. Also, have they experienced withdrawal symptoms if they decreased or stopped taking their usual dose? Some patients may perceive the anxiety of inter-dose withdrawal (or otherwise when attempting to taper) as evidence that the taper is a failure or that they have an underlying anxiety disorder, when they may simply be exhibiting mild withdrawal. Lastly, assessing for other psychoactive or sedating substance use is important to understand risk. This can include alcohol and opioids, but also substances that may go under the radar, like antihistamines, muscle relaxants, or gabapentinoids.

CATR: You mentioned benzodiazepine-related risks. Some people are calling benzodiazepines the “new opioids.” Are we entering a benzodiazepine crisis?
Dr. Morford: I think that it’s important to recognize the differences between benzodiazepines and opioids. First of all, in terms of some of their differences, benzodiazepines are considered a safer medication largely because they do not impact respiratory depression the same way that opioids do. Benzodiazepines are a Schedule IV controlled substance, as opposed to opioids that are Schedule II. But benzodiazepines clearly do have potential for misuse, similar to opioids. And we see that there are serious risks of benzodiazepine use, especially when combined with other CNS depressants like opioids or alcohol (Jones JD et al, Drug Alcohol Depend 2012;125(1–2):8–18; Hernandez I et al, JAMA Network Open 2018;1(2):e180919). One recent national study demonstrated that benzodiazepine co-involvement in opioid-related overdoses has increased over the last two decades; benzodiazepines were involved in 21% of such deaths in 2017 (Tori ME et al, JAMA Network Open 2020;3(4):e202361). Finally, a major risk of chronic benzodiazepine use is the development of physical dependence that leads to risk of withdrawal, which can include life-threatening events such as seizures.

CATR: Given the risks of combining CNS depressants, what clinical considerations should we keep in mind when seeing patients who are prescribed benzodiazepines and who also have opioid use or alcohol use disorder?
Dr. Morford: This is an important question and is very relevant to my clinical practice. Most of my patients have substance use disorders and may come to me already receiving a benzodiazepine prescription. Most importantly, especially for patients with opioid use disorder, we don’t withhold medications for opioid use disorder, such as methadone and buprenorphine, simply because a patient is also taking a benzodiazepine. This is consistent with the recently released ASAM Guidelines for the Management of Opioid Use Disorder (Crotty K et al, J Addict Med 2020;14:99–112). The other important consideration here is making sure that patients with opioid use disorder are receiving an adequate dose of those medications. Oftentimes, I’ll see that patients are receiving a lower dose of methadone or buprenorphine because the provider is worried about the concurrent use of benzodiazepines, and that can bring patients to use benzodiazepines as a way to self-medicate withdrawal symptoms. We may be setting those patients up to fail. So, one of my first steps is to make sure that the methadone or buprenorphine dose is adequate.

CATR: Do you ever question the need for the benzodiazepine in the first place, or discuss tapering?
Dr. Morford: If a patient is receiving benzodiazepines from another prescriber and not receiving first-line therapy, it’s important to connect with that other provider to discuss the case and come up with a coordinated plan. Despite limited data, current guidelines recommend that we taper benzodiazepines to discontinuation, especially for patients who have co-occurring substance use disorders, and this is the approach I try to take (SAMHSA, Tip 63: Medications for Opioid Use Disorder; www.tinyurl.com/y7kbv6ot). The benefits of a taper, when successful, can be enormous: less risk for sedation, of course, but patients can also report functional improvement, more clarity in thinking, and improved sleep over time. The risks, however, generally apply to overly rapid tapers, which can produce withdrawal symptoms—including irritability and insomnia—and can also encourage patients to disengage from care if they’re not convinced the taper is in their best interest.

CATR: So the guidelines suggest that we should not withhold treatment for opioid use disorder because of benzodiazepine use. However, if we do go down that route, we should strongly consider a benzodiazepine taper.
Dr. Morford: Yes. You may be familiar with the FDA’s initial communication in 2016 that prescribers should avoid combining benzodiazepines and opioids at all costs. However, there wasn’t clear guidance on what to do with medications like methadone and buprenorphine that are opioids but are being used to treat opioid use disorder. So a year later in 2017, the FDA came out with an updated statement that clearly said that we should not withhold those medications from patients who are taking benzodiazepines, but have opioid use disorder that needs to be treated.

CATR: Despite these new recommendations, have you found that methadone programs may still consider benzodiazepine found in urine toxicology a reason for discharge or at least decreasing the methadone dose?
Dr. Morford: We see that a lot. That is not a practice that I recommend, and most guidelines don’t recommend that methadone doses should be tapered just based on the fact that someone is using a benzodiazepine (Food and Drug Administration, 2017; www.tinyurl.com/td648oq). When we see evidence of impairment, that’s really the time to think about decreasing the dose of methadone to optimize safety, but it really shouldn’t be done simply due to the presence of benzodiazepine metabolites in toxicology testing.

CATR: What do we know about treatment of patients with benzodiazepine use disorder?
Dr. Morford: Here, the recommendation is also to taper to discontinuation. We don’t have great medications specifically to treat benzodiazepine use disorder, so typically it will require coming up with a patient-specific taper plan, depending on how risky the situation seems. If this is somebody we’re really worried about having withdrawal seizures, then we might want to recommend an inpatient facility, but more often it can be done in outpatient settings. Tapering can be successful at a dose-reduction rate of about 5%–10% per week or month. Addition of an anticonvulsant, like gabapentin, can be considered for high-dose withdrawal. Switching to a longer-acting benzodiazepine (clonazepam, diazepam) may make for a more tolerable tapering experience.

CATR: Are there meds that you recommend to help patients during the time period they are tapering off benzodiazepines?
Dr. Morford: We can make the taper more tolerable by providing medications like hydroxyzine, clonidine, or trazodone to help people sleep and help with anxiety. These medications may be tapered over a period from several weeks to 6 months. The reality is that you’re going to make progress on the taper as best you can, in partnership with the patient. (Editor’s note: Also see CATR, May 2016 on benzodiazepine tapering, and TCPR, Jan 2019 on deprescribing.)

CATR: Any specific guidance on how to discuss tapering with patients?
Dr. Morford: When someone is coming and seeking help for benzodiazepine use disorder, they’re seeking treatment because something about the benzodiazepine use has become problematic in their lives. So, we should use motivational interviewing strategies to reaffirm that their use has caused problems and make sure that, in addition to the formulation and plan, we provide education about the risks associated with benzodiazepines. I’m often surprised that patients who may know quite a bit about the harms of opioids may know less about the harms of benzodiazepines, so education is a key component at the outset of a taper. Frequent follow-up and expressing non-abandonment is important, too. When patients make an initial step in a taper, they sometimes notice they feel better, and this can be motivating.

CATR: Thank you for your time, Dr. Morford.