CATR: Please introduce yourself.

Dr. Rastegar: I’m an internist by training, practicing in addiction medicine for about 30 years. I am at Johns Hopkins Bayview Medical Center, where I provide primary care with a focus on people with substance use disorders (SUDs), and I am the medical director for our inpatient withdrawal management unit. I’m also the program director for the addiction medicine fellowship.

CATR: How common is it for patients to have multiple SUDs?

Dr. Rastegar: I would say it’s more the rule than the exception. Most people that we see are using multiple substances, and if you include nicotine, it’s almost a universal phenomenon. Most concerning is the use of opioids in combination with other central nervous system (CNS) depressants because of the high risk of mortality. Alcohol and other sedatives are also concerning because of the risk of medication complications during withdrawal. And these are drugs that we tend to focus on when managing withdrawal medically: alcohol, sedatives, and opioids. 

CATR: Do certain substances tend to cluster together?

Dr. Rastegar: To my knowledge, there aren’t any definitive data on that front, but we do see patterns. For example, stimulant use commonly goes along with alcohol or opioids. And I’ve found that it’s uncommon to see patients who are misusing sedatives alone—almost all of them are also using opioids or some other drug. On the flip side, there are many people who use alcohol or opioids pretty much exclusively. 

CATR: What are some challenges in assessing patients who are using multiple substances?

Dr. Rastegar: The challenges aren’t all that different from patients who use a single substance. You should stick to the basic principle of starting with a thorough patient interview, getting a good history, and finding out what they’ve been using. In most circumstances, you’ll be treating patients who are voluntarily seeking care, so I’ve found they are generally forthcoming. But there are challenging situations that can make history-gathering tough. Sometimes patients may not disclose which substances they have been using because of stigma or potential legal consequences. Other times, patients may be intoxicated, which makes it difficult to gather a good history. And especially during withdrawal, patients can be irritable and uncooperative. Withdrawal is uncomfortable, and these are not very happy patients. 

CATR: And how do you handle these situations?

Dr. Rastegar: An open, accepting approach can be helpful. Reassure the patient that we are here to help. And we can get information through laboratory testing—an alcohol level through breath or serum can tell us if the patient has been drinking recently. A urine drug screen will tell us about use of some other substances. If they are intoxicated, wait until their alcohol level comes down. If they are irritable due to being in withdrawal, starting with empiric treatment can make them much more comfortable.

CATR: Patients withdrawing from more than one substance may experience multiple withdrawal syndromes simultaneously. That can be challenging to assess because many of the symptoms overlap. How do you sort through all that?

Dr. Rastegar: It’s true that some withdrawal symptoms are not all that specific. You can’t always say, “This symptom is due to withdrawal from alcohol and this other symptom is due to withdrawal from opioids” when the patient has been using both substances—it doesn’t usually work like that. Irritability is probably a universal symptom during withdrawal, regardless of substance. Diaphoresis, anxiety, and restlessness are seen with both alcohol and opioid withdrawal, while we typically think of tremors as only accompanying alcohol or sedative withdrawal. Piloerection and dilated pupils are pretty specific to opioid withdrawal, though they may not be present. And of course, we think of gastrointestinal complaints with opioid withdrawal, but those can come with alcohol as well. 

CATR: How do you treat patients who are presenting with overlapping withdrawal syndromes?

Dr. Rastegar: The general approach is to treat both withdrawal syndromes independently. You shouldn’t substantially change your clinical approach to treating alcohol withdrawal just because the patient is also withdrawing from opioids. Alcohol withdrawal is more likely to lead to serious complications, so I would prioritize that. 

CATR: Tell us about your approach to opioid withdrawal.

Dr. Rastegar: Withdrawal management alone for opioid use disorder (OUD) is not adequate treatment. The standard of care is to start a medication for OUD (MOUD), either buprenorphine or methadone. Many have had experience with one or both medications and have a preference. If they want methadone, you can start them on methadone 30 mg and titrate up. The trick with methadone is ensuring that patients have follow-up in a federally recognized opioid treatment program (OTP), aka a “methadone clinic.” Federal regulations limit methadone prescribing to three days; after that, patients need to be part of a methadone prescribing program. A preference for buprenorphine can be a little more complicated because of the risk of precipitated withdrawal during initiation. There are a few approaches to starting buprenorphine (Editor’s note: See “Three Buprenorphine Dosing Strategies When Transitioning From Other Opioids” in CATR Apr/May/Jun 2024). In my personal practice, which is in an inpatient setting, I sometimes give 30 mg of methadone up front if the patient is in severe withdrawal, just to stabilize them, and then use a low-dose initiation of buprenorphine, also called microinduction. Injectable naltrexone can of course be a good long-term treatment, but it does not treat symptoms of withdrawal.

CATR: And what about alcohol and sedative withdrawal?

Dr. Rastegar: Benzodiazepines are the treatment of choice for alcohol withdrawal. We use a symptom-triggered protocol with a scoring system that we developed as an alternative to the familiar Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). If the patient’s withdrawal goes above a certain threshold, we give a benzodiazepine, usually diazepam. Diazepam is certainly not the only medication you could use, but I prefer long-acting agents because you don’t have to medicate patients as frequently. The exception is in patients with severe liver disease, specifically those with decompensated cirrhosis or evidence of synthetic dysfunction (elevated PT, INR, or total bilirubin). In those circumstances, the standard practice is to use lorazepam (Editor’s note: For more about management of alcohol withdrawal, see our interview with Dr. Brian Fuehrlein in CATR Jan/Feb/Mar 2023).

CATR: You developed a different scoring system to assess alcohol withdrawal severity?

Dr. Rastegar: Yes, we found that the CIWA-Ar didn’t work well for us. It has 10 items, so it’s cumbersome, and it relies on subjective measures like anxiety and nausea. Most of the items are scored on a 0–7 scale and the definitions of each score are not really spelled out; what differentiates a 4 from a 5 from a 6, for example? So, we developed the Brief Alcohol Withdrawal Scale (BAWS), which has five items: 1) tremor, 2) diaphoresis, 3) agitation, 4) confusion/disorientation, and 5) hallucination (Rastegar D et al, Subst Abus 2017;38(4):394–400). Each item is scored 0–3, with a maximum of 15. Higher scores trigger higher medication doses and more frequent patient assessment (Editor’s note: See the table for more details). It’s been easy to implement and works well for us. At this point, it is the standard tool across the Johns Hopkins medical system. Importantly for your readers in particular, the scale has been validated for use in psychiatric settings as well (Elefante RJ et al, J Addict Med 2020;14(6):e355–e358).

CATR: And what about sedatives?

Dr. Rastegar: You can certainly utilize benzodiazepines for people who are withdrawing from sedatives. That’s one way to go, but for patients taking high doses of non-prescribed benzodiazepines, we find that a phenobarbital taper works better. Those patients are hospitalized, and we give a fixed dose taper starting with 100 mg doses and tapering down to 60 mg doses; we hold doses for sedation. (Kawasaki SS et al, J Subst Abuse Treat 2012;43(3):331–334). 

CATR: The medications we’ve discussed so far are all CNS depressants. Providers may be concerned about giving agents with potentially synergistic CNS-depressing effects. 

Dr. Rastegar: This may be a concern in theory, but I can’t say that we find it to be much of a problem in practice. We do a lot of comanagement of withdrawals, so we are often giving benzos and/or phenobarbital along with methadone or buprenorphine, and if the patients are being carefully monitored, it’s rarely problematic. Remember, withdrawals occur because patients have built up tolerance, and most of our patients have very high levels of tolerance. If anything, I think we more often undermedicate our patients. Sometimes a patient becomes sedated. If that’s the case, back off on the dosage or just wait for them to become more alert. We are typically using symptom-triggered protocols anyway, so if the patient is sedated, they aren’t going to get additional medication. On the other hand, if the patient is agitated and/or confused despite high doses of sedatives, they should be referred for ICU care.

CATR: We have been primarily discussing hospitalized patients. Which patients can be treated on an outpatient basis?

Dr. Rastegar: Deciding on the proper setting is the first decision to make. Outpatient can be appropriate for patients who aren’t at risk for severe or complicated withdrawal and who have a fairly stable living situation, particularly if there is another person at home who can help monitor them.

CATR: And how does your clinical approach differ in the outpatient setting?

Dr. Rastegar: In terms of alcohol withdrawal, the main difference is that I use symptom-triggered protocols in the hospital, which we have already discussed, and a standing benzodiazepine taper for outpatients. I typically use chlordiazepoxide for outpatient alcohol withdrawal, starting with a dose of 50 mg for a day or two and then going down to 25 mg for two to three more days. If the patient does not have a history of severe or complicated withdrawals, gabapentin 300–400 mg three times a day is a reasonable option as well. For opioids, the goal is still to get patients onto MOUD, regardless of treatment setting. The difference here is that outpatient methadone must be started at an OTP, whereas buprenorphine can be started in the ambulatory setting. Outpatient buprenorphine induction can be very successful and achieved in several ways (Editor’s note: See interview with Dr. Capurso in CATR Nov/Dec 2021). But returning to the topic of comorbid withdrawal, I think it is quite challenging to manage withdrawal from multiple substances on an outpatient basis. For these patients, I would recommend inpatient or residential treatment, at least until they are stabilized.

CATR: What are some other important considerations when treating these patients?

Dr. Rastegar: We’ve talked about alcohol, sedatives, and opioid withdrawals already, and those are certainly the ones that need active treatment. However, we often forget that patients withdraw from stimulants, nicotine, cannabis, and even caffeine.

CATR: What should we do about these? We don’t think of them as requiring specific treatment. 

Dr. Rastegar: It’s true that they don’t require specific medications beyond simple comfort measures, but comfort measures are important to remember. Withdrawing from these drugs, which many of us don’t even think of as having withdrawal at all, can be incredibly uncomfortable. Provide NSAIDs and acetaminophen if the patient has pain or a headache, give nicotine replacement, and provide a sleep medication if the patient has trouble sleeping. Not only does paying attention to these needs help the patient feel heard and validated, it may also help us avoid a patient leaving prematurely against medical advice. The key here is to talk to your patient, find out what they need help with, and strive to be as responsive as you can.

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