Caridad Ponce Martinez, MD, FAPA, FASAM.
Assistant professor of psychiatry, UMass Chan Medical School, Worcester, MA.
Dr. Ponce Martinez has no financial relationships with companies related to this material.
CHPR: How can we make sure not to miss the symptoms of alcohol withdrawal among patients who are admitted to psychiatric emergency departments or inpatient units?
Dr. Ponce Martinez: Make sure to ask about the patient’s pattern of alcohol use and explore whether there has been a recent reduction or cessation after chronic alcohol use. Keep in mind that a blood alcohol level of zero is not necessary for someone to experience alcohol withdrawal.
CHPR: So a patient may present with symptoms of alcohol withdrawal, even though they still appear intoxicated.
Dr. Ponce Martinez: Among patients with chronic, heavy drinking, that’s correct.
CHPR: What screening tests do you use in your evaluation of alcohol withdrawal?
Dr. Ponce Martinez: I like to use the Alcohol Use Disorders Identification Test (AUDIT), the AUDIT-C, or the CAGE questionnaire. A positive screening test tells me I need to do an additional evaluation to determine the risk for alcohol withdrawal (Editor’s note: For an AUDIT-C calculator, see: www.tinyurl.com/bdc8fxbd).
CHPR: Which patients are at particular risk for complications of alcohol withdrawal?
Dr. Ponce Martinez: The patients at highest risk are those who have previously experienced severe alcohol withdrawal symptoms. Elderly patients and patients with other medical conditions or complications, like severe liver disease or seizure disorders, are also at elevated risk. So are patients who, because of their underlying psychiatric conditions, might not be able to readily communicate as their symptoms worsen.
CHPR: What are the typical symptoms of alcohol withdrawal?
Dr. Ponce Martinez: They range from mild to severe. During mild alcohol withdrawal, patients may experience nausea, vomiting, tremulousness, diaphoresis, sensitivity to light or sound, headache, anxiety, insomnia, and restlessness. For most patients, symptoms tend to be mild or moderate, but I ask if they have ever experienced more severe symptoms: hallucinations, seizures, or delirium tremens (DTs). It’s important to identify patients who have experienced these more severe symptoms so that we can be prepared to manage them in advance. DTs is rare but can be lethal, so I watch for symptoms carefully. Historically the mortality rate of DTs was as high as 20%, although due to better medical management, it is now 1%–4% (Turner RC et al, J Gen Intern Med 1989;4(5):432–444). Patients sometimes mistake tremulousness with DTs, so I’ve learned to be very descriptive of what I’m referring to—alcohol withdrawal plus rapid-onset, fluctuating confusion or disorientation 72–96 hours after stopping/reducing alcohol use. I also ask whether the patient has ever needed to be admitted to a medical hospital or intensive care unit (ICU) for the management of their alcohol withdrawal symptoms. This can help me anticipate greater withdrawal symptom severity.
CHPR: Over what timeframe do withdrawal symptoms appear?
Dr. Ponce Martinez: Mild symptoms occur as early as six hours after the last drink. Again, that is from a reduction or cessation in drinking to when they present; it does not need to be abstinence. Symptoms can take as long as 36 hours to appear, although typically you’ll see symptoms within 24 hours of the last drink. Different symptoms have different times of manifestation: Withdrawal seizures can occur six to 48 hours later; alcoholic hallucinosis, meaning hallucinations with intact sensorium, can occur 12–48 hours later; and DTs typically occurs 48–96 hours after alcohol reduction or cessation. There is some nuance in the timing of these symptoms—particularly when there are other substances of abuse or medications like benzodiazepines, barbiturates, opioids, other sedatives, or beta-adrenergic antagonists—that may mask or even worsen some of the withdrawal symptoms. Some of the cases I monitor most closely are patients who have taken benzodiazepines, since the appearance of alcohol withdrawal symptoms may be delayed.
CHPR: How do you distinguish the hallucinations of DTs from schizophrenia?
Dr. Ponce Martinez: The hallucinations from alcohol withdrawal are transient and new in onset, as opposed to those of a patient with schizophrenia. The hallucinations can be auditory, visual, or tactile, and range from mild perceptual distortions to frank hallucinations. Interestingly, visual hallucinations from alcohol withdrawal syndromes are often of animals (Wartenburg AA. Management of alcohol intoxication and withdrawal. In: Miller SC, Fiellin DA, Rosenthal RN, Saitz R, eds. The ASAM Principles of Addiction Medicine. 6th ed. Philadelphia, PA: Wolters Kluwer; 2019:704–722). Patients may also experience formication, or tactile hallucinations: the sensation of bugs crawling on their skin. When the hallucinations are present with delirium and autonomic instability, the patient is experiencing DTs. However, hallucinations can be present on their own, which is referred to as alcoholic hallucinosis.
CHPR: Are there any other symptoms of withdrawal that may be confused with symptoms of other psychiatric conditions/disorders?
Dr. Ponce Martinez: Mild withdrawal symptoms, including tremulousness, insomnia, and anxiety, can be confused with anxiety disorders; the timeline of these symptoms and their appearance in the context of alcohol cessation or reduction can be a helpful way to distinguish between the two. Irritability, restlessness, and insomnia could also be confused with a hypomanic state.
CHPR: How do you monitor the progression of alcohol withdrawal symptoms?
Dr. Ponce Martinez: The Clinical Institute Withdrawal Assessment–Alcohol Revised (CIWA-Ar) scale is a helpful tool. There are other scales for patients with severe symptoms who can’t communicate, but for the patients we typically see in a psychiatric unit, the CIWA-Ar scale is appropriate (Editor’s note: The CIWA-Ar scale can be found here: www.tinyurl.com/3hpetse8). Of note, the CIWA-Ar requires repeat administration so you can see the trajectory of the symptoms of alcohol withdrawal. Mild symptoms, meaning a CIWA-Ar score less than 8, include headache, gastrointestinal symptoms, and tremulousness. Scores of 8–15 indicate moderate withdrawal symptoms, and scores greater than 15 indicate severe alcohol withdrawal with impending DTs. These patients need to be transferred rapidly to a medical unit or ICU.
CHPR: Besides CIWA-Ar scores of greater than 15, what other reasons would you have to transfer someone from a psych unit to a medical unit for the treatment of withdrawal?
Dr. Ponce Martinez: For stand-alone psychiatric units where there is limited medical support, I would recommend caution when admitting patients who have a history of moderate to severe alcohol withdrawal, or who are experiencing withdrawal symptoms despite a high blood alcohol content, or who have risk factors for complicated alcohol withdrawal, like concomitant withdrawal from other substances. This is because psychiatric units usually lack the ability to rapidly escalate medical care if necessary, including transfer to a medical unit. Another reason to transfer patients to a medical unit is for intravenous (IV) treatment if they can’t take medications by mouth because of severe nausea and vomiting. And patients who require monitoring more frequently than every two hours are typically not appropriate for inpatient psychiatric units.
CHPR: Would you send a patient to a medical unit if their blood alcohol level is over a certain limit?
Dr. Ponce Martinez: Not necessarily, as a blood alcohol level is just one piece of information in my evaluation of a patient. But I would be concerned if a patient presented with a high blood alcohol level yet exhibited alcohol withdrawal symptoms, as this would indicate that the patient has a high tolerance and is at risk of severe withdrawal symptoms.
CHPR: What pharmacologic protocol do you follow for the management of withdrawal?
Dr. Ponce Martinez: The standard of care involves use of benzodiazepines, and I use the CIWA-Ar to guide the treatment. There are several protocols about how to administer benzodiazepines, and there is certainly a lot of personal and institutional preference for which benzodiazepines to use, but there’s no particular benefit of one benzodiazepine over another. When selecting benzodiazepines, I consider factors like liver function and age. For elderly patients, I worry about co-occurring medical conditions or other sedating medications and prefer shorter-acting agents, like lorazepam (Ativan), that can be easily titrated and are less likely to cause excessive sedation. A concern with excessive sedation is that patients will be at risk of respiratory depression and aspiration.
CHPR: What do you do for patients who have mild or moderate symptoms and no medical complications?
Dr. Ponce Martinez: For those patients, especially if they aren’t taking other sedating medications, I prefer to use longer-acting agents, like chlordiazepoxide (Librium) 50–100 mg/dose and diazepam (Valium) 10–20 mg/dose. These medications provide longer relief and require less frequent dosing. Diazepam has the added advantage of rapid-onset symptom relief and active metabolites, which can prolong the effect. And longer-acting agents are less reinforcing, which is an important consideration in patients with alcohol use disorder (AUD). But I like using lorazepam as it is one of the easiest benzodiazepines to titrate. One option for treatment for patients at moderate or severe risk for complications of alcohol withdrawal involves providing benzodiazepines on a fixed-dose regimen, for example lorazepam 2 mg every four hours or chlordiazepoxide 50 mg every six hours. It’s important to monitor the need for more medication if the fixed dose is inadequate. Therefore, lorazepam 2 mg can additionally be ordered as needed every four hours if the CIWA-Ar score is ≥8. The CIWA-Ar is repeated one hour after every dose. It’s helpful to calculate the total dose of benzodiazepines received over a 24-hour period when assessing the effectiveness of a medication regimen and considering a taper to, for example, 1 mg of lorazepam every four hours. But, if a patient has required 2 mg of lorazepam six times over the course of 24 hours, and CIWA-Ar scores have ranged between 8 and 16, these high CIWA-Ar scores indicate that a taper is not recommended at this time because the patient may actually need even higher doses of benzodiazepines.
CHPR: Do you also use symptom-triggered treatment, and can you describe this treatment approach?
Dr. Ponce Martinez: Symptom-triggered treatment involves using patients’ scores on a standardized scale to determine when to dose a benzodiazepine. We use the CIWA-Ar and prescribe a benzodiazepine if the score reaches a threshold of ≥8, then we evaluate the symptoms one hour later, again using the CIWA-Ar. Another approach is the loading-dose strategy, where we provide repeated doses of a long-acting benzodiazepine—for example, diazepam 10–20 mg hourly—until the withdrawal symptoms decrease or there are signs of oversedation, and we monitor for several hours without further medication, and the benzodiazepine level then decreases naturally. Different strategies can be used in combination. If a patient is on symptom-triggered therapy but requires dosing every hour due to persistent CIWA-Ar scores ≥8, then a fixed-dose therapy may be preferred. This would allow the withdrawal symptoms to be treated more aggressively, thereby preventing development of more severe symptoms.
CHPR: Do you use any medications besides benzodiazepines?
Dr. Ponce Martinez: Yes, phenobarbital can be used, primarily in medical units and ICUs. But even for patients with very severe withdrawal symptoms, benzodiazepines are effective. Non-benzodiazepine anticonvulsants, like carbamazepine, valproic acid, and gabapentin, are also options (Amato L et al, Cochrane Database Syst Rev 2011;6:CD008537; Wartenburg, 2019) but don’t seem to be superior to benzodiazepines. Benzodiazepines are the only medications with FDA approval for treatment of alcohol withdrawal.
CHPR: What are the advantages of using antiepileptic medications for alcohol withdrawal?
Dr. Ponce Martinez: Anticonvulsants are helpful not only because of their low abuse potential, but also because of their potential “anti-kindling effect” as the risk of seizures increases with repeated episodes of alcohol withdrawal. And anticonvulsants don’t increase cravings or heighten the risk to relapse to alcohol use, unlike benzodiazepines.
CHPR: For how long do you prescribe them?
Dr. Ponce Martinez: I continue some anticonvulsants long term. Several studies have looked at the use of gabapentin for the long-term management of alcohol withdrawal symptoms (Anton RF et al, JAMA Intern Med 2020;180(5):728–736; Ahmed S et al, Prim Care Companion CNS Disord 2019;21(4):19r02465). Gabapentin does not have FDA approval for alcohol withdrawal, but at 1200 mg daily, in divided doses three or four times daily, it helps target protracted withdrawal symptoms like insomnia, anxiety, and irritability. These symptoms can be a significant risk factor for relapse to alcohol use following an episode of detoxification.
CHPR: How long do these protracted withdrawal symptoms last?
Dr. Ponce Martinez: They can last weeks to months after cessation of alcohol use, particularly if untreated.
CHPR: What are your dosing considerations when using antiepileptic drugs?
Dr. Ponce Martinez: I aim for therapeutic blood levels, but one thing to consider with many of these medications is that they undergo hepatic metabolism, so for patients with alcohol-related liver disease, they may not be an option. Gabapentin is an exception as it’s renally excreted and is safe to use in patients with liver disease.
CHPR: What about beta blockers like propranolol for anxiety and tremor?
Dr. Ponce Martinez: While they often provide symptomatic relief, they can be problematic because they mask some of the autonomic symptoms of alcohol withdrawal and make it difficult to utilize scales like the CIWA-Ar to guide treatment.
CHPR: Do you also treat patients’ nutritional deficiencies?
Dr. Ponce Martinez: Yes, I do. Most patients who present with AUD are at risk of thiamine deficiency, which can lead to Wernicke’s encephalopathy (WE) and/or Korsakoff’s syndrome, so I provide thiamine supplementation. In the inpatient psychiatric unit, I dose it orally at a minimum of 100 mg PO daily for three days and continue the oral supplementation for several weeks. In the medical units, thiamine is administered IV or intramuscularly. This supplementation is particularly important before any administration of glucose, to avoid precipitation of WE (Editor’s note: See article on WE in this issue). Patients are likely to have folic acid, pyridoxine (vitamin B6), and other nutritional deficiencies, so I usually prescribe them a daily multivitamin.
CHPR: Once patients are past the withdrawal symptoms and ready for discharge, do you send them out with medications like naltrexone or acamprosate?
Dr. Ponce Martinez: The answer is absolutely, yes. Medications for AUD are effective and significantly underused throughout our medical system. Once patients are ready for discharge, we have an opportunity to educate them about the available treatments to help decrease cravings for alcohol and support their treatment goals with regard to AUD, whether that is reduction or cessation of use. One great option for patients with AUD is extended-release naltrexone, which we can administer prior to hospital discharge. It’s a monthly injectable medication, but patients may prefer oral naltrexone because they don’t like injections or have a hard time obtaining the injection in the community. Acamprosate is another option, at a dose of 666 mg three times daily. Off-label medications like topiramate, gabapentin, and baclofen can also be helpful in the treatment of AUD.
CHPR: Thank you for your time, Dr. Ponce Martinez.
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