Tae Woo (Ted) Park, MD. Assistant professor, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.
Dr. Park has no financial relationships with companies related to this material.
CATR: Let’s start by discussing appropriate uses for benzodiazepines (BZDs).
Dr. Park: In terms of mental health conditions, BZDs are primarily used to treat anxiety disorders such as panic disorder and generalized anxiety disorder (GAD). Some are approved for insomnia as well. In psychiatry, they are very important in the treatment of agitation and mania, usually in combination with an antipsychotic or mood stabilizer, as well as catatonia. Finally, a BZD taper is the standard of treatment for management of alcohol and BZD withdrawal.
CATR: Do you recommend that BZDs only be used as needed, or is chronic use okay?
Dr. Park: Ideally, BZDs should be prescribed as needed or for the short term and after safer alternatives have failed, like how prescribed for pain. In terms of pharmacologic alternatives, SSRIs and SNRIs are often used as first-line treatments for anxiety disorders; these should be tried first. Anxiolytics, like hydroxyzine and buspirone, can be helpful for some patients. Gabapentinoids that have demonstrated effectiveness for GAD can also be used before BZDs, though they carry their own risks, such as misuse and overdose potential when combined with opioids (Generoso MB et al, Int Clin Psychopharmacol 2017;32(1):49–55).
CATR: But these other less risky interventions don’t always work.
Dr. Park: And that’s when the BZD may need to come in. Realistically, we have to acknowledge that many of the conditions BZDs are used for are chronic by their very nature, like GAD. The general practice is to start a less risky medication along with the BZD, like an SSRI or SNRI, with the idea that the BZD can provide some short-term relief while the other medications are taking effect. That’s a good strategy, but unfortunately, it doesn’t always work out in the real world. Guidelines caution against chronic BZD administration, and we should avoid doing so whenever possible, but patients may end up on them anyway if other medications aren’t effective. It’s not always so clear cut.
CATR: What about psychotherapy?
Dr. Park: Psychotherapy is a great option and can play a crucial role in managing anxiety and panic. There is a robust evidence base that some manualized forms of therapy, like cognitive behavioral therapy (CBT), can help patients develop coping strategies and address the underlying causes of their anxiety. CBT can be an effective stand-alone treatment or used in conjunction with medication. Another advantage here is that effects can be long lasting, whereas medication stops working once it’s discontinued. A challenge is that therapy can be time-consuming, and patients need to be willing and able to fully engage to derive maximum benefit. And for many patients, access is a problem.
CATR: Which patient demographics pose higher risks when prescribing BZDs?
Dr. Park: There are two major groups to be cautious with. The first is older adults, especially those with medical comorbidities such as sleep apnea. They are at risk for falls, fractures, and cognitive issues. In older patients, BZDs can cause a picture that can easily be confused with a neurocognitive disorder, or cause delirium.
CATR: And what’s the second group?
Dr. Park: The second group is people with substance use disorders (SUDs). They are at an increased risk of addiction to BZDs, of course, though a primary BZD addiction is relatively rare (Park TW, J Addict Med 2017;11(2):87–89). In my experience, these patients are using BZDs to treat another underlying condition, but they have a history of addressing discomfort with a substance, so they are prone to misuse and adverse outcomes. The bigger worry is that those with opioid use disorder (OUD) are at higher risk of overdose if they are taking BZDs, due to the combined central nervous system (CNS) and respiratory depressant effects. We also know that BZDs are associated with worse outcomes in those with alcohol use disorder (Day C. Benzodiazepines in combination with opioid pain relievers or alcohol: greater risk of more serious ED visit outcomes. In: The CBHSQ Report. Rockville, MD: Substance Abuse and Mental Health Services Administration (US); 2013:1–9).
CATR: How do you approach prescribing for patients who have SUDs? Do you ever do it, or is it contraindicated?
Dr. Park: It’s not absolutely contraindicated, though I always exercise a bit more caution. People with addiction to CNS depressant drugs tend to have a higher preference for BZDs in drug administration studies (Woods JH et al, Pharmacol Rev 1992;44(2):151–347). Regular monitoring is crucial, particularly when prescribing to high-risk groups. In this population, I recommend urine drug testing as a monitoring method. I’m less worried about patients with stimulant use disorders because a stimulant and BZD are not going to synergistically raise risk of overdose. The caution there is if a patient is using the BZDs to treat a side effect of excessive stimulant use, like insomnia. You don’t want your BZD prescription to just facilitate further stimulant use. Many people with stimulant use disorder do use BZDs that way, and so it’s not surprising that the prevalence of misuse is high in this population (Votaw VR et al, Drug Alcohol Depend 2019;200:95–114). If I have a patient with a positive result for cocaine, for example, that can spark a conversation about what’s going on, how I can support them, and whether the BZD is helping or harming them.
CATR: How do you discuss BZDs with patients, particularly at the start of treatment?
Dr. Park: It’s essential to set expectations from the beginning. I’m explicit that even though I’m prescribing it, the medication is not risk free. I go over the risk of physical dependence with long-term use. And I stress that ideally the medication is for the short term. If they are at higher risk, such as having an SUD history, I tell them up front about any urine toxicology or prescription monitoring that is going to happen. I’ll lay out the conditions under which the BZD will be discontinued: urine drug screens indicating other drug use and to verify that the medication is being taken instead of sold, multiple requests for early refills, “lost” medications. The conversation varies depending on the patient’s risk level. For example, if a patient has had a BZD prescription in the past, they are familiar with their effects. I don’t need to spend lots of time explaining how the medication might make them sleepy. For patients with addiction, I stress the risks of misuse—risks of combining BZDs with other drugs like opioids. I talk about the difference between prescribed BZDs versus ones bought on the street that might contain fentanyl or something else (Editor’s note: See CATR May/June 2022 for additional information about urine drug screens).
CATR: How do different BZD agents compare in terms of effectiveness and safety?
Dr. Park: There are two main factors to consider here: half-life and lipophilicity. Half-life determines how long the medication effects last, and lipophilicity tells you the time of onset because drugs with high lipophilicity will cross the blood-brain barrier faster. Diazepam (Valium) and alprazolam (Xanax) have high lipophilicity and therefore faster onset of action. This can increase the risk of misuse. Short half-life medications (eg, alprazolam) can lead to more severe withdrawals. Patients will be more uncomfortable coming off short half-life drugs and can have more complications like seizures if the initial tolerance is high enough. Longer half-life medications, like diazepam, warrant caution too since they can build up in the system if taken more frequently than recommended (Editor’s note: See “Benzodiazepines: The Basics and Beyond” for more comparative analysis of BZDs).
CATR: Putting this all together, which agents do you prefer for treating a condition like GAD or panic disorder?
Dr. Park: I often lean toward clonazepam (Klonopin), and that tends to be my first-line preference whether the patient has an SUD or not. Most patients respond to it, even though it doesn’t have a very rapid onset of action. You’d think that for an indication like panic disorder, you would want a highly lipophilic drug, but that is not necessarily the case. Lorazepam (Ativan) is a reasonable choice for similar reasons. And I almost always start with prescribing on an as-needed basis. I’ll give them a few tablets for the month and tell them to use it sparingly when they’re feeling like they’re about to have a panic attack.
CATR: Any tips for minimizing tolerance?
Dr. Park: In my experience, I rarely run into issues with tolerance when the medication is being taken correctly. I have patients who have been on a stable dose for years, and rarely do they ask for more. If they are requesting higher and higher doses, that raises a red flag that something else might be going on, like misuse or diversion.
CATR: What warning signs might lead you to reevaluate a BZD prescription?
Dr. Park: First, most people whom I prescribe BZDs to are going to do fine with the medication. If they have an OUD, I try to prescribe a BZD only if they are on a stable and effective dose of a medication for the OUD. Again, these are people for whom I feel the risk-benefit calculation favors giving them the medication. But I do occasionally give them to higher-risk patients. In that group, I recommend regular drug testing. Pay attention to how the patient looks clinically. If your patient has an OUD and they’re being prescribed a BZD and they come in looking sedated, then immediately I’m worried. I’ve had patients come in and say “There’s nothing wrong with me. I’m fine. I’m fully awake.” And they’re falling asleep in the office. Don’t ignore signs like that.
CATR: Any other warning signs?
Dr. Park: If possible, keep an eye on the medical chart. You might have a patient present to your office requesting a refill for BZDs who looks fine. But if you do a little chart digging, maybe they were in the emergency room with an opioid overdose. That’s a patient whom you will want to get off BZDs as soon as you safely can. Your state’s prescription drug monitoring program can alert you if your patient is “doctor shopping.” And then there are the more usual signs that you look for—multiple early refill requests, inconsistent urine toxicology testing, and as I mentioned before, need for escalating doses.
CATR: How do you handle patients who request multiple early refills?
Dr. Park: My initial approach is to see these patients more frequently and distribute smaller amounts of medication over shorter periods: weekly visits instead of monthly appointments, for example. That’s a place to start. However, if the issue persists or other monitoring methods indicate illicit drug use, discontinuation might be necessary. This can be challenging, and some clinicians are hesitant to prescribe BZDs to high-risk patients for this reason.
CATR: And if you decide that someone’s BZD does need to be stopped, what then?
Dr. Park: Do your best not to make it into a confrontation. It sometimes happens, but that’s never productive. If I discover that a patient is misusing their BZD, my first step is to have an open conversation about their usage. I always do my best to ensure that the patient understands my rationale. They may not agree to it, but it’s important that to them it does not seem like an arbitrary or punitive decision. Stress the importance of safety, that you are willing to find safer ways to help them feel better. Often, just asking them about their misuse becomes an opportunity to explore further treatment options, rather than a fight. For example, a patient’s misuse might be due to inadequate management of anxiety symptoms, which could require a change in treatment plan. If the misuse is related to an SUD, I might refer the patient to a specialized addiction treatment program, if one is available. And I assure them that I will be stopping the medication as safely and comfortably as possible.
CATR: What does discontinuing look like?
Dr. Park: I do not abruptly discontinue BZDs unless the dose is very low. Tapering should be performed gradually and under close supervision, always considering the patient’s individual circumstances. I usually opt for a rate of about 10%–25% every one to two weeks—tapers can often last eight weeks or longer depending on how long the patient has been taking the drug. Tapers should not be rigid. Watch the patient and adjust accordingly (Editor’s note: For more on tapering strategies, see our interview with Dr. Abelleira in this issue).
CATR: Any tips for providers dealing with patients using non-prescribed BZDs obtained from friends, family, or the street?
Dr. Park: As a harm reductionist, I sometimes prefer to have control over a patient’s medication rather than having them take unregulated substances from the street. For certain carefully selected patients, sometimes those who report taking street BZDs in a therapeutic manner, prescribing a known dose and monitoring them closely might be a safer option than leaving them to source their own BZDs. This approach might be seen as controversial by some, but it should be considered on a case-by-case basis. It is essential to educate patients about the risks associated with obtaining pharmaceuticals from unregulated sources. These drugs may be counterfeit (aka “pressed pills”), contaminated with fentanyl, or contain variable doses, increasing the risk of adverse effects or overdose (Editor’s note: See CATRJul/Aug/Sep 2023 for more on illicit drugs and fentanyl testing).
CATR: Thank you for your time, Dr. Park.
PO Box 626, Newburyport MA 01950