TCPR: When should we consider benzodiazepines?
Dr. Morehead: Let’s start with their FDA indications. Most are indicated for the short-term relief of anxiety or insomnia, and the FDA defines “short term” as less than 4 months for anxiety or less than 10–28 days for insomnia. Some benzodiazepines have indications in specific anxiety disorders, like panic disorder (alprazolam and clonazepam) and generalized anxiety disorder (alprazolam). In social anxiety disorder, they have good evidence but lack an indication. Those are the areas where we have the best evidence, but I don’t see benzos as first line for any of those conditions. They are not recommended in OCD, where they failed to make a difference in trials, nor in PTSD, where they may interfere with exposure therapy and worsen long-term outcomes (Guina J et al, J Psychiatr Pract 2015;21(4):281–303).

TCPR: What are some of the pros and cons of using a benzo for anxiety disorders, particularly as most anxiety disorders are long term?
Dr. Morehead: The pros are that they work rapidly. They work for all kinds of anxiety, and they might be more effective than the selective serotonin reuptake inhibitors (SSRIs), although that’s arguable and patient dependent. They tend to be well tolerated overall, and patients like taking them. That, however, is also a downside, as they can be self-reinforcing and lead to overuse and misuse. The cons also include cognitive side effects and the risks of falls, car accidents, and respiratory suppression, especially when benzos are combined with opioids or alcohol.

TCPR: How is tolerance different from misuse and abuse?
Dr. Morehead: Misuse is when patients use the benzo at times other than as directed, such as taking more than prescribed during a panic attack. Misuse is not automatically regarded as “abuse.” Abuse is when patients take the benzo for recreational nonmedical reasons, and a substance use disorder is when that leads to a destructive pattern of use. Tolerance is when the effects go down with repeated use, which can happen after misuse, abuse, or just routine medical use. Dependence is a more ambiguous word that has gone out of favor, as it can refer to either physical tolerance or a substance use disorder.

TCPR: How much do we need to worry about these various issues?
Dr. Morehead: We do need to be wary of abuse and addiction, but in proportion to the problem. The literature tells us that: 1) Benzodiazepines are not nearly as reinforcing as drugs like opioids or cocaine/amphetamines, and 2) Benzodiazepines are much more self-reinforcing in defined subgroups of patients. So, patients with a history of substance use disorders are at high risk for misusing or abusing benzodiazepines, and that’s often regarded as a contraindication. Other groups at higher risk of misuse include young adults (ages 15–35), and individuals who enjoy moderate alcohol even if they don’t have alcohol use disorder. In one survey, 51% of people ages 18–25 reported misuse of their benzodiazepines versus 4% of people over 65. On the other hand, in long-term studies of patients treated by doctors with benzodiazepines, rates of dose escalation are very low—7% or less (Maust DT et al, Psychiatr Serv 2019 Feb 1;70(2):97–106).

TCPR: How do you use benzos in practice?
Dr. Morehead: When I start a benzo, it is usually in a patient whose anxiety disorder has not responded to first-line and sometimes second-line treatments. That includes SSRIs and serotonin/norepinephrine reuptake inhibitors, but also psychosocial options such as psychotherapy, cognitive techniques, muscle relaxation, deep breathing, exercise, and meditation. In general, I’d want the patient to be in some form of psychotherapy if they’ve reached the point where they need to take a benzo. However, I often inherit patients who come to me on a benzo.

TCPR: How do you handle that?
Dr. Morehead: I start by comparing the risk of continuing the medicine versus coming off it. Untreated anxiety disorders have significant medical risks, so it’s not risk free just to avoid benzodiazepines. While studies on benzodiazepine discontinuation show mixed results, a recent large study showed that mortality rates actually went up when researchers tried to take patients off benzos—even in populations where these medications are more risky, like the elderly and those on opioids (Maust DT et al, JAMA Netw Open 2023;6(12):e2348557). I try to enlist the patient in a joint undertaking where we’re both trying to figure out what is best for their anxiety and their health. These aren’t paternalistic times anymore where we can just tell patients what to do.

TCPR: Tell us more about that study where the mortality went up off the benzos. 
Dr. Morehead: It was a large study of a commercial insurance database, but it was not randomized, so we can’t be sure that other confounding variables weren’t responsible for the mortality rates, although the researchers did try to control for known confounders. It does reinforce what we see anecdotally, as there are lots of stories of people who have a horrible time getting off these medications. So when a patient is reluctant to come off a benzo, it may not be because the drug is rewarding. Rather, it could be that they feel the medicine is working or fear withdrawal symptoms. We need to be very careful in deciding whether to take people off benzodiazepines just as we are with other medicines, like antidepressants and mood stabilizers. And we should taper slowly when we take that step.

TCPR: We seem to approach benzos differently. We discourage patients from staying on them and spend a lot of time convincing patients to stick with their other meds.
Dr. Morehead: Yes, there’s a moral undertone that benzodiazepines are some kind of self-indulgent drug that we shouldn’t be prescribing because we have “real” medicines like SSRIs. This muddies the waters, which is part of the reason both the public and professionals are so divided on their use.

TCPR: It sounds like we might misinterpret the distress of withdrawal as drug-seeking behavior. 
Dr. Morehead: Yes. There is also a bias toward seeing psychiatric symptoms as less important than other medical symptoms. I remind myself regularly that anxiety disorders carry a higher risk of heart attacks, stroke, and risk of increased mortality overall. We shouldn’t just tell people to put up with their subjective distress.

TCPR: And there’s no perfect way to measure distress. 
Dr. Morehead: Medicine is based on probabilities. For any given patient, we are making an educated guess based on probabilities, and even the right decision doesn’t guarantee the right outcome. We could have a bad outcome with the right decision, and certainly plenty of my decisions are wrong.

TCPR: When did medicine become less paternalistic?
Dr. Morehead: In the 1950s and 1960s, doctors were the authority. The doctors had the knowledge and made the decisions. Some doctors did not tell patients about their diagnosis or treatment, and some even prescribed placebos without the patient knowing. Since then, there has been a gradual shift toward patient autonomy and rights. That means patients need to understand the risks and benefits of their treatments. Ideally, the decision-making and the risks are shared. Values make a big difference here. Some patients don’t want to take any risks of car accidents or falls, while others are willing to accept those risks. But even with these cultural shifts, there are still gray zones, like the way that the legal system holds us responsible for decisions as if the patient is completely passive and makes no choices of their own.

TCPR: Benzos are also controlled substances, which makes shared decision-making difficult and raises additional concerns about legal liability.
Dr. Morehead: Yes. No one can read minds or predict the future, so what we go by is the actual evidence in front of us. We aren’t detectives, but it’s our job to keep our eyes open, and if the patient shows signs of substance misuse, we need to take those very seriously and act on them. At the same time, we need to give patients the benefit of the doubt because trust is part of treatment. When there’s a problem or when we are using an unusual treatment regimen, I tell patients that many doctors would question the way we’re doing this and why.

TCPR: How do you document your decision-making with benzos?
Dr. Morehead: I document that we discussed risks and benefits, including specific risks like driving and falls. I often write, “This patient has severe and treatment-resistant symptoms, and given the failure of other options, the risk of the benzodiazepine appears justified.”

TCPR: There’s some recognition of shared decision-making in the 2021 overhaul of the evaluation and management CPT^® codes, which pay by complexity of visit and shared decision-making. They recommend we specify that, “The medication plan was developed through shared decision-making with the patient, with consideration of the efficacy and safety of the medications and the patient’s preferences in treatment.”
Dr. Morehead: Yes, that’s very helpful to put in the note. Shared decision-making is the standard, but it doesn’t include things that are dangerous and destructive. You have to know your boundaries.

TCPR: What is outside your safety zone with benzos? 
Dr. Morehead: I try to avoid benzos in patients who are taking opioids, who have substance use disorders, or who have borderline and antisocial personality disorders. One risk with benzos is disinhibition, and there are case reports of sudden violence or self-harm after taking them. I would also avoid them in anyone who has a history of benzodiazepine or opioid overdose.

TCPR: What are your thoughts about as-needed (PRN) versus scheduled use?
Dr. Morehead: Scheduled use has a lower risk of misuse and abuse than PRN. In my experience, this is especially true for patients who have severe, chronic anxiety. There’s a strong pull to chase rapid, full remission by taking more and more of a benzodiazepine. I’ll tell these patients that it isn’t realistic to expect the benzo to stop all of their anxiety. If it helps 50%, that’s good, but it doesn’t mean that doubling the dose will take care of the rest of the problem.

TCPR: Are there situations where you’d prefer PRN?
Dr. Morehead: Yes, in simple phobia, like when a patient only needs it for flying on an airplane. I also use PRN for patients who are very conscientious and truly will take the medicine only when necessary. For that group, we go by the rule of thumb that they shouldn’t need the PRN benzodiazepine more than 50% of days. If they’re taking it more often than that, then I feel like it’s an indication to reassess and make it scheduled or try something else.

TCPR: Do you favor any particular benzos in particular scenarios?
Dr. Morehead: I try to avoid diazepam and alprazolam, which are more prone to abuse and also have a higher overdose risk.

TCPR: How do you manage benzo tapers?
Dr. Morehead: The classic approach is to take a patient who’s on a shorter-acting benzodiazepine and switch them to something longer-acting like diazepam, but this is not always easy, and I often end up tapering what they have. But I think the most important thing is the alliance. If I want the patient off the benzo and they want to stay on it, they will have more anxiety and things will go poorly. I make it a joint project and emphasize treatments like cognitive technique, self-relaxation, psychotherapy, and other medicine options. Then I educate about withdrawal symptoms and reassure them that we’re going to go slowly and sensitively. Classically, we can taper the first 50% of the dose more quickly. But for long-term benzo users, the latter part of the taper may have to proceed quite slowly.

TCPR: Thank you for your time, Dr. Morehead.