Purpose of This Guideline
Date of current publication: July 30, 2020
Lead authors: Yonina Mar, MD, Mount Sinai Beth Israel, and Hillary Kunins, MD
Writing group: Chinazo O. Cunningham, MD, MS; Sharon Stancliff, MD; Lyn C. Stevens, MS, NP, ACRN; Christopher J. Hoffmann, MD, MPH; Charles J. Gonzalez, MD
Committee: Substance Use Guidelines Committee
Date of original publication: July 30, 2020
This guideline on the treatment of alcohol use disorder (AUD) was developed by the New York State Department of Health AIDS Institute (NYSDOH AI) to guide primary care providers and other practitioners in New York State in treating individuals with AUD.
This guideline aims to:
- Increase the number of clinicians in outpatient settings offering evidence-based treatment to individuals with AUD.
- Increase the number of New York State residents with AUD who are engaged in treatment.
- Reduce the number of alcohol-related deaths in New York State.
- Promote a harm reduction approach to treatment of AUD, which involves practical strategies and ideas aimed at reducing the negative consequences associated with alcohol use.
Alcohol use disorder in the United States: In the 2018 National Survey on Drug Use and Health in the United States, the Substance Use and Mental Health Services Administration (SAMHSA) reported that an estimated 14.8 million individuals aged 12 or older in the United States had AUD, based on Diagnostic and Statistical Manual of Mental Disorders-IV criteria SAMHSA 2019. SAMHSA also reported that approximately:
- 67.1 million individuals engaged in binge drinking on at least 1 day within the past 30 days, defined as 5 or more drinks at 1 occasion for men and 4 or more for women.
- 16.6 million individuals aged 12 or older engaged in heavy drinking within the past 30 days, defined as binge drinking on 5 or more days SAMHSA 2019.
The most recent available analysis of alcohol-related mortality in the United States was based on death certificates and indicated that, among individuals aged 16 years and older, death rates due to alcohol increased by 50.9% between 1999 and 2017. In 2017, 2.6% of approximately 2.8 million deaths in the United States involved alcohol, with liver disease and alcohol overdose or overdose with alcohol and other drugs accounting for nearly half of alcohol-related deaths White, et al. 2020.
Role of primary care providers in the treatment of alcohol use disorder: Primary care providers in New York State can play an essential role in identifying and treating AUD in their patients. There are effective pharmacologic and psychosocial treatments for AUD that can be delivered in an outpatient setting, which can increase access to evidence-based treatment for individuals with AUD. Because primary care may lend itself to long-term, continuous relationships, this treatment setting lends itself well to managing AUD, a chronic health condition, because it allows for ongoing follow-up.
Goals of Treatment for Alcohol Use Disorder and Treatment Options
Choosing a Treatment Option
Goals of Treatment
A traditional goal of treatment for alcohol use disorder (AUD) is long-term cessation of alcohol use. Because this goal may not be achievable for many individuals, alternative goals can lead to substantial improvements in the health and lives of those with AUD. Such alternatives may include:
- Staying engaged in care, which can also facilitate prevention, diagnosis, and treatment of other conditions
- Reducing alcohol use
- Reducing high-risk behaviors (e.g., driving while intoxicated, alcohol-related unprotected sex)
- Improving quality of life and other social indicators, such as employment, stable housing, and risk of incarceration
- Improving mental health
As with other chronic conditions, treatment goals for AUD should be individualized and are likely to change over time. It is important for healthcare providers and patients to discuss, agree on, and review AUD treatment goals regularly. If patients are unable to meet treatment goals, intensifying treatment with frequent visits, behavioral interventions, mental health assessment and treatment, and adjustment of dose or type of medication may be warranted.
Pharmacologic Treatment Options
Currently, 3 medications are approved by the U.S. Food and Drug Administration (FDA) for the treatment of AUD: acamprosate, naltrexone, and disulfiram. Gabapentin and topiramate are additional evidence-based options for treatment. All of these medications are available in oral formulations, and naltrexone is also available in an extended-release (XR) formulation for intramuscular injection.
Based on strong clinical evidence, acamprosate and oral or XR naltrexone are the preferred pharmacologic treatments for individuals with moderate-to-severe AUD who have a goal of reducing or abstaining from alcohol use SAMHSA 2015; Jonas, et al. 2014. In individuals with mild AUD, clinicians may consider pharmacologic treatment with oral acamprosate or oral or XR naltrexone.
Clinical trials directly comparing acamprosate and naltrexone have not consistently established the superiority of one medication over the other in reducing heavy drinking. Individuals who use alcohol primarily for positive reinforcement (reward drinkers) may benefit more from naltrexone than those who drink for negative reinforcement, such as avoiding withdrawal (relief drinkers) Mann, et al. 2018. There is minimal and mixed evidence on whether combining naltrexone and acamprosate has an additive effect on alcohol consumption outcomes Anton, et al. 2006; Kiefer, et al. 2003.
Acamprosate: Alcohol withdrawal produces a neurobiologic derangement in neuronal gamma-aminobutyric acid type A (GABAA), N-methyl-D-aspartic acid (NMDA), and glutamate transmission, which can result in an excitotoxic state and neuronal injury. Acamprosate modulates transmissions from GABAA and NMDA receptors, which can restore neuronal balance and mitigate the associated symptoms Kalk and Lingford-Hughes 2014.
In clinical trials that have compared treatment with acamprosate and placebo, acamprosate increased the proportion of individuals who maintained complete abstinence from alcohol (complete abstinence rate), the mean cumulative abstinence duration, the percentage of alcohol-free days, and the median time to first drink Higuchi 2015; Plosker 2015; Gual and Lehert 2001; Tempesta, et al. 2000; Geerlings, et al. 1997; Pelc, et al. 1997; Poldrugo 1997; Sass, et al. 1996; Whitworth, et al. 1996; Paille, et al. 1995. A meta-analysis from 2014 found that acamprosate was significantly associated with decreased return to any drinking and with decreased percentage of drinking days throughout treatment Jonas, et al. 2014. Acamprosate should be initiated as soon as the individual has abstained from alcohol use (within 7 days) for the best treatment response. Acamprosate can be initiated if the individual is still actively using alcohol, but the efficacy of treatment during active alcohol use is unknown.
Naltrexone: Naltrexone is an opioid receptor antagonist used in the treatment of individuals with AUD or opioid use disorder (OUD). Alcohol use increases the activity of the endogenous opioid system. As an opioid receptor antagonist, naltrexone interferes with the rewarding aspects of alcohol Ray, et al. 2010; Pettinati, et al. 2006; Mason, et al. 2002. Naltrexone may also decrease subjective cravings for alcohol Maisel, et al. 2013. A meta-analysis found no significant difference in alcohol consumption, a measure combining study-specific outcomes, between naltrexone and acamprosate treatment Jonas, et al. 2014; Mann, et al. 2013; Anton, et al. 2006; Morley, et al. 2006; Kiefer, et al. 2003.
Clinical trials have shown that naltrexone improves alcohol use outcomes and, specifically, decreases the likelihood of return to drinking and the overall number of drinking days Jonas, et al. 2014. A meta-analysis of studies evaluating treatment with oral naltrexone showed that oral naltrexone 50 mg daily was associated with decreased return to any drinking and decreased return to heavy drinking, and XR naltrexone was associated with reduced heavy drinking days Jonas, et al. 2014. An ongoing randomized controlled trial by Lee, et al., is examining the effectiveness of oral versus XR naltrexone in producing abstinence or moderate drinking Malone, et al. 2019. Studies have shown that naltrexone is more effective in reducing alcohol consumption in individuals who use nicotine or cigarettes compared with those who do not Anton, et al. 2018; Fucito, et al. 2012, which may be one factor in selecting pharmacologic treatment. Active alcohol use is not a contraindication to initiating treatment with naltrexone (oral and XR formulations); however, individuals should be monitored for alcohol withdrawal syndrome if alcohol use is significantly reduced abruptly.
Disulfiram: Disulfiram inhibits the enzyme aldehyde dehydrogenase, which breaks down acetaldehyde, an alcohol byproduct. Consuming alcohol while taking disulfiram results in an accumulation of acetaldehyde and adverse reactions such as low blood pressure, tachycardia, facial flushing, nausea, vomiting, dyspnea, sweating, dizziness, blurred vision, and confusion. This adverse reaction is called the disulfiram-ethanol reaction Bell and Smith 1949. The psychological threat of these unpleasant physiologic effects is believed to be the primary mechanism for dissuading alcohol use in individuals with AUD Skinner, et al. 2014.
Evidence is mixed on the effectiveness of disulfiram for the treatment of AUD. Well-controlled clinical trials do not support an association between disulfiram use and improvement in alcohol consumption outcomes Jonas, et al. 2014. However, it may be difficult to evaluate disulfiram in a double-blind study design because the threat of the physiologic effects of combining alcohol and disulfiram, which is present for both treatment and control groups, is directly related to the efficacy of the drug Skinner, et al. 2014. A meta-analysis showed that disulfiram was effective at improving consumption outcomes in open-label trials (no blinding for participants or researchers) but not effective in blinded randomized controlled trials Skinner, et al. 2014.
Since the 1970s, studies examining the effectiveness of disulfiram have typically compared unsupervised administration of disulfiram with administration supervised by health professionals or by suitable delegated associates of the participant. Results suggest that disulfiram can be an effective treatment with supervised administration, but adherence is low with unsupervised administration Brewer, et al. 2017; Skinner, et al. 2014; Jørgensen, et al. 2011; Fuller, et al. 1986. Active alcohol use is a contraindication to disulfiram. At least 12 hours of abstinence from alcohol is required before initiating treatment with disulfiram to avoid an adverse reaction. Individuals should be warned that reactions may occur if alcohol is consumed up to 14 days after taking disulfiram.
Gabapentin: The mechanism of action of gabapentin in treating AUD is not fully understood. However, evidence suggests that gabapentin modulates and stabilizes central stress systems that are dysregulated by the cessation of alcohol use Roberto, et al. 2010; Roberto, et al. 2008.
Although gabapentin is not approved by the FDA for treatment of AUD, use of this medication has been associated with reductions in alcohol use and craving Mason, et al. 2018; Mason, et al. 2014. In addition, as an adjunct to benzodiazepines, gabapentin is effective in treating common symptoms of acute and protracted alcohol withdrawal, including anxiety and sleep disturbances Mason, et al. 2018; Rosenberg, et al. 2014; Lavigne, et al. 2012; Myrick, et al. 2009; Brower, et al. 2008; Bazil, et al. 2005; Karam-Hage and Brower 2000. Active alcohol use is not a contraindication to initiating gabapentin Myrick, et al. 2007.
Topiramate: The mechanism of action of topiramate in treating AUD is not fully understood. However, evidence suggests that topiramate enhances GABAergic neurotransmission and suppresses glutamatergic neurotransmission, helping to normalize and restore balance in the reward circuits of the brain Cheng, et al. 2018; Frye, et al. 2016; Shank and Maryanoff 2008.
Like gabapentin, topiramate is not approved by the FDA for treatment of AUD, but it has been associated with fewer drinking days, fewer drinks per drinking day, decreased percentage of heavy drinking days, and increased number of abstinent days Manhapra, et al. 2019. To a lesser degree, topiramate has been associated with reduced cravings for alcohol Manhapra, et al. 2019.
The effectiveness of topiramate for AUD does not appear to be substantially affected by whether or not the individual was abstinent from alcohol or underwent detoxification from alcohol before treatment. This suggests that topiramate can be used successfully in individuals who are unwilling or unable to achieve abstinence before treatment Maisel, et al. 2013.
|Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) and DSM-5 Diagnoses||
Behavioral treatment: In general, behavioral treatment for AUD is delivered in a specialty addiction treatment program. In addition to offering patients pharmacologic treatment, clinicians should refer patients for psychological interventions, based on individual needs, social factors, preferences, and resources.
Many studies support the effectiveness of motivational interviewing (MI), motivational enhancement therapy (MET), and cognitive behavioral therapy (CBT) for treating individuals with AUD Miller 2018; DiClemente, et al. 2017; Lenz, et al. 2016; Lundahl, et al. 2013; Smedslund, et al. 2011; Lundahl, et al. 2010; Magill and Ray 2009, including studies conducted in the primary care setting VanBuskirk and Wetherell 2014; Lundahl, et al. 2013; Stecker, et al. 2012. Evidence is mixed about whether the combination of pharmacologic treatment with a structured psychosocial intervention leads to better outcomes than pharmacologic treatment alone for individuals with AUD Anton, et al. 2006.
MI, MET, CBT, and other approaches have been incorporated into many interventions for treatment of AUD. Variables in studies of behavioral interventions for alcohol use make it difficult to compare and interpret the evidence and extrapolate it to “real-world” settings and individual patients. These variables include type of approach, duration and number of sessions, type and training of the healthcare provider delivering the intervention, treatment setting, mode of delivery (in person or computerized), individual or group setting, risk level of alcohol use or AUD, and concurrent pharmacologic treatment. Most clinical trials examining pharmacologic treatment include a psychological component (e.g., MI or CBT for all treatment groups).
MI is a way of helping patients recognize their current or potential problems and take action toward resolving them. The overall goal of MI is to increase the patient’s intrinsic motivation to facilitate change from within, and the method is particularly useful for patients who are ambivalent about changing behavior or who are reluctant to change Miller and Rollnick 2002. This technique emphasizes the autonomy of the patient while providing a safe space for collaboration and consistent engagement to enhance the patient’s motivation for change. The MI approach also helps the clinician identify the patient’s readiness to change behavior and to use the patient’s level of readiness as a starting point for counseling or treatment. It is worthwhile for healthcare providers to understand and use an MI-style approach when discussing alcohol use and AUD treatment plans with patients and to be aware of clinician and patient resources (see Online Resources: Behavioral Treatment for Alcohol Use Disorder, below).
The key principles of MI are:
- Express empathy/avoid arguing
- Develop discrepancy
- Roll with resistance
- Support self-efficacy (patient’s belief they can successfully make a change)
MET, adapted from MI principles, is a manual-based intervention designed to help patients explore ambivalence about alcohol use and develop intrinsic motivation to reduce or abstain from alcohol use Lenz, et al. 2016. CBT, individually or in groups, focuses on how thoughts, feelings, and behaviors influence each other and can be particularly useful for helping patients recognize and manage individual triggers for alcohol use. For CBT in an online format, see Computer Based Training for Cognitive Behavioral Therapy (CBT4CBT).
Other behavioral approaches include mindfulness and contingency management. A mindfulness approach seeks to help individuals with SUDs, including AUD, monitor for and relate differently to internal and environmental cues that trigger substance use Bowen, et al. 2014. Mindfulness-based relapse prevention programs have been associated with significant improvements in some alcohol-related outcomes compared with other psychosocial interventions, but data are limited Grant, et al. 2017; Bowen, et al. 2014. Contingency management aims to improve SUD treatment outcomes, such as engagement in care or abstinence, by providing incentives to patients. Studies have shown that contingency management was associated with significant improvements in alcohol-related outcomes, but the approach is not feasible in most medical settings Getty, et al. 2019; Barnett, et al. 2017; McDonell, et al. 2017; Benishek, et al. 2014; Dougherty, et al. 2014; Prendergast, et al. 2006.
Mutual support programs: Self-Management and Recovery Training (SMART Recovery) focuses on self-empowerment and provides mutual support through in-person group meetings and online formats. The program uses rational emotive behavior therapy, a form of CBT, to facilitate changes in thinking and thus in emotions and behaviors Horvath and Yeterian 2012. Some studies have shown positive alcohol-related treatment outcomes, but data are inconsistent Beck, et al. 2017. Some patients may find benefit in and connection to Alcoholics Anonymous (AA), a 12-step, mutual-support group approach based on fellowship and the role of a higher power. A recent systematic review identified high-quality evidence indicating that AA and 12-step facilitation interventions were at least as effective in increasing abstinence and improving alcohol-related outcomes as clinical psychological interventions (e.g., MET, CBT, other 12‐step program variants) Kelly, et al. 2020. In some AA programs, however, participants who take pharmacologic medication for AUD can be made to feel unwelcome.
|ONLINE RESOURCES: BEHAVIORAL TREATMENT FOR ALCOHOL USE DISORDER|
Medical Management Treatment Manual
Mutual Support Programs
Choosing a Treatment Option
Clinicians should collaborate with patients to set specific treatment goals about patient alcohol use and should document the treatment plan they agree on in the medical record APA 2017; Dunn and Strain 2013. Individual goals in the treatment plan may include, but are not limited to, abstinence, reduction in alcohol use, or avoiding alcohol consumption in high-risk situations (e.g., at work, before driving, when caring for children).
If pharmacologic treatment is initiated, clinicians should schedule frequent follow-up visits to provide patients with support and encouragement and to monitor treatment response, possible adverse effects, medication adherence, and signs of continued use or return to use. If a patient continues to use alcohol, pharmacologic treatment options, except for disulfiram, can be continued. However, clinicians should discuss treatment goals and possible modifications to the treatment plan with the patient.
Adherence is essential for pharmacologic treatments to be effective, making pill burden an important practical consideration for clinicians. Treatment with acamprosate requires patients to take 2 pills thrice daily, and treatment with naltrexone requires patients to take 1 pill once daily.
The choice of behavioral treatment for AUD is based on patient experience and preference, social factors, treatment availability, and insurance, among other individual factors.
Implementing Pharmacologic Treatment for AUD in the Primary Care Setting
Managing Withdrawal Syndrome
Initiating Pharmacologic Treatment
Managing Alcohol Withdrawal Syndrome
Before initiating AUD treatment, clinicians should determine if patients are experiencing withdrawal syndrome. If symptoms are present, clinicians should assess withdrawal severity using a validated instrument, such as the Clinical Institute Withdrawal Assessment for Alcohol, Revised (CIWA-Ar) or the self-completed 10-item Short Alcohol Withdrawal Scale (SAWS), which has been validated in the outpatient setting Muncie, et al. 2013; Elholm, et al. 2010; Gossop, et al. 2002; Sullivan, et al. 1989.
In individuals with AUD, an abrupt cessation or significant reduction of alcohol use can precipitate an acute withdrawal syndrome within 4 to 12 hours of last alcohol use APA 2017. The syndrome may persist for as long as 5 days, and symptoms range from anxiety, agitation, tremor, and sympathetic nervous system activation to more serious outcomes such as seizure and delirium tremens, which can result in death if not treated APA 2017.
In most individuals, mild to moderate alcohol withdrawal syndrome can be managed in the outpatient primary care setting Muncie, et al. 2013 with benzodiazepines Schaefer and Hafner 2013; Mayo-Smith 1997. The Prediction of Alcohol Withdrawal Severity Scale (PAWSS) is a validated screening instrument for predicting the development of severe alcohol withdrawal. A PAWSS score < 4 is considered low risk for complicated alcohol withdrawal syndrome and may help to identify individuals that can be managed in the outpatient primary care setting Wood, et al. 2018; Maldonado, et al. 2015. For recommendations on treating alcohol withdrawal syndrome, see American Society of Addiction Medicine (ASAM): Clinical Practice Guideline on Alcohol Withdrawal Management.
Gabapentin is also effective in treating common symptoms of acute and protracted alcohol withdrawal, including anxiety and sleep disturbances Mason, et al. 2018; Mason, et al. 2014. Gabapentin and other anticonvulsants, including carbamazepine and valproic acid, have been studied as alternatives to benzodiazepines for managing alcohol withdrawal syndrome, but data are limited. These medications have less potential for misuse and may be safer, particularly if mixed with alcohol. However, anticonvulsants do not prevent alcohol withdrawal seizures or delirium tremens. Ideally, individuals treated for alcohol withdrawal syndrome in the outpatient setting should be assessed daily until their withdrawal symptoms decrease, and the medication dosage can be reduced and eventually discontinued. For an increased likelihood of success in the outpatient setting, patients should be able to take oral medications, be committed to frequent follow-up visits, or have a relative, friend, or caregiver who can stay with them and administer medication Blondell 2005.
Patients who have severe alcohol withdrawal symptoms should be referred to a detoxification or inpatient setting for intensive management Myrick and Anton 1998 (see PAWSS for assessing the level of severity). Referral for intensive management of alcohol withdrawal may be appropriate for patients who have:
- A history of long-term heavy alcohol use
- Acute or chronic comorbidities, including serious mental illness
- A history of withdrawal seizures or high risk of delirium tremens
- Concurrent use of other drugs
Initiating Pharmacologic Treatment
Clinicians should initiate treatment with acamprosate as soon as the individual has abstained from alcohol use (within 7 days) for the best treatment response. Acamprosate can be initiated if the individual is still actively using alcohol, but the efficacy of treatment during active alcohol use is unknown.
Because acamprosate is excreted through the kidneys, clinicians should measure CrCl before starting treatment. Dose reduction may be necessary for patients with CrCl between 30 and 50 mL/min or eGFR between 30 and 59 mL/min/1.73 m2. Acamprosate may be a good option for patients with AUD who have significant hepatic dysfunction because it is not metabolized through the liver and has no reported risk of hepatotoxicity.
Acamprosate has been most effective as an AUD treatment in individuals with high levels of motivation Jonas, et al. 2014. Clinicians should work with patients to assess and enhance motivation (e.g., via motivational interviewing). Acamprosate should be initiated as soon as possible after alcohol withdrawal (within 7 days) and may be maintained if the individual continues or returns to alcohol use.
Induction and maintenance: Oral acamprosate is typically started and continued as 3 doses daily, two 333 mg tablets for each dose for a total of 1998 mg daily.
Adverse effects: Acamprosate is generally well tolerated; the most frequently reported adverse effect in clinical trials was diarrhea Sinclair, et al. 2016; Chick, et al. 2000; Lhuintre, et al. 1985. If diarrhea is severe, a temporary dose reduction may be beneficial Sinclair, et al. 2016; Chick, et al. 2000; Lhuintre, et al. 1985.
Active alcohol use is not a contraindication to initiating treatment with naltrexone (oral and XR formulations).
In clinical studies, high adherence to oral naltrexone, defined as pills taken on more than 80% to 90% of days, was necessary to achieve significant treatment effects Srisurapanont and Jarusuraisin 2005; Chick, et al. 2000. Assessing and supporting a patient’s ability to adhere to oral naltrexone before starting treatment (e.g., via motivational interviewing) is essential. Engaging family members or others to assist with adherence to oral naltrexone can be helpful.
XR naltrexone may improve adherence compared to oral naltrexone Hartung, et al. 2014. XR naltrexone is administered as a 380 mg intramuscular gluteal injection every 28 days (alternating buttocks for each subsequent injection). When an XR naltrexone injection is delayed beyond 28 days, clinicians can provide the patient with a prescription for daily oral naltrexone (50 mg daily) to take until they can receive the injection.
Naltrexone is contraindicated in individuals with acute hepatitis or liver failure; therefore, baseline assessment of liver function should be performed before treatment initiation. Naltrexone is a preferred treatment option in patients with AST/ALT levels lower than 3 to 5 times the upper limit of normal Kwo, et al. 2017; Turncliff, et al. 2005. Clinicians can also consider performing follow-up liver tests 4 to 12 weeks after initiating naltrexone treatment Lucey, et al. 2008. The extent of liver abnormalities may guide continued testing or referral to an experienced liver specialist.
Induction and maintenance (oral): The recommended induction and maintenance dose of oral naltrexone is 50 mg daily. However, a dose of 100 mg daily was used and well tolerated in the large COMBINE trial Anton, et al. 2018, so a dose increase may be considered.
Induction and maintenance (injectable): The recommended induction dose is 50 mg oral naltrexone once daily for at least 3 days to assure that the patient tolerates the medication. A maintenance dose is 380 mg naltrexone administered as an intragluteal injection every 28 days.
Individuals with AUD who also use opioids should be abstinent from opioids for approximately 7 to 14 days before initiating XR naltrexone, which is considered an alternative treatment for OUD. Clinicians should confirm the length of time since last opioid use by performing a naloxone challenge. Administer a single intranasal dose (2.0 mg/0.1 cc) of naloxone and confirm the response. In individuals with recent opioid use, this may precipitate opioid withdrawal. If a patient is already taking oral naltrexone, a naloxone challenge is not necessary.
Adverse events: Oral and XR naltrexone are generally well tolerated. The more common adverse events include gastrointestinal symptoms, such as nausea , vomiting, abdominal pain, diarrhea, and dizziness FDA 2013; FDA 2010. Gastrointestinal adverse events associated with naltrexone may be more common among women than among men Herbeck, et al. 2016. If an individual experiences adverse events with oral naltrexone, clinicians can consider a reduced dose of 25 mg Anton 2008.
XR naltrexone can cause pain or hardening of soft tissue at the injection site. The potential for bleeding at the injection site in individuals who have coagulopathy or are taking anticoagulants should be considered. Sufficient adipose tissue is required for injection and may be difficult in an individual who is cachectic.
Disulfiram is contraindicated in individuals who are actively using alcohol. Clinicians should consider it a treatment option only for individuals with a clear goal of abstaining from alcohol. If alcohol is consumed within 12 hours of taking disulfiram, the accumulation of acetaldehyde produces a severe physiologic response. It is essential to educate patients about avoiding medications or common products that contain alcohol, such as cough and cold medicines, mouthwashes, tonics, sauces, vinegar, and other food or skin products, because they may precipitate this adverse reaction.
Disulfiram does not reduce an individual’s cravings for alcohol; instead, it provides an adverse reaction to alcohol use. Thus, motivation and consistent adherence are required for disulfiram to be effective as a deterrent to alcohol use. In clinical trials, individuals who chose disulfiram as their preferred treatment and were highly adherent or were receiving disulfiram under supervision achieved the greatest success Johnson 2008; Laaksonen, et al. 2008; O'Farrell, et al. 1995; Chick, et al. 1992.
Disulfiram has been associated with mild increases in hepatic enzymes in approximately 25% of individuals taking the medication Björnsson, et al. 2006. Acute and potentially fatal hepatotoxicity is very rare (1 per 10,000 to 30,000 years of disulfiram treatment) Björnsson, et al. 2006. Clinicians should perform baseline liver function testing, including AST/ALT tests, before initiating treatment with disulfiram and consider initiating disulfiram if AST/ALT levels are lower than 3 to 5 times the upper limit of normal Kwo, et al. 2017. It may be useful for clinicians to obtain follow-up liver test results within 1 month of initiating treatment. The extent of liver abnormalities may guide continued testing or referral to a liver specialist. In addition, disulfiram is not considered safe in individuals with serious medical comorbidities (e.g., cardiovascular disease) or serious mental illnesses (e.g., psychotic disorders) FDA 2015.
Induction and maintenance: The initial dose of disulfiram is up to 500 mg once daily for 1 to 2 weeks. The recommended maintenance dose of disulfiram is 250 mg daily (range, 125 mg to 500 mg).
Adverse events: Consuming alcohol while taking disulfiram can result in the adverse reactions described in the Good Practices, above. Because disulfiram is contraindicated in patients with coronary artery disease or recent myocardial infarction, it may be appropriate to assess cardiac function before starting treatment with disulfiram. Disulfiram is not recommended for patients with seizure disorders or a history of psychosis. Caution should be taken in prescribing disulfiram to patients who have a family history of psychosis FDA 2015.
At doses of up to 1800 mg daily, gabapentin is safe and well tolerated in individuals with AUD Mason, et al. 2018; Mason, et al. 2014. Abstinence from alcohol is not a requirement for initiating gabapentin treatment; there are no adverse interactions reported when alcohol and gabapentin are consumed at the same time Myrick, et al. 2007. Gabapentin has been increasingly associated with opioid-related overdose deaths; caution is required when prescribing gabapentin for individuals with comorbid AUD and opioid use disorder Chiappini and Schifano 2016.
Gabapentin is excreted through the kidneys, and clinicians may consider performing tests for serum creatinine levels, particularly when administering high doses of gabapentin. Dose reduction may be necessary for patients with reduced renal function. Because gabapentin is not metabolized through the liver and has no reported risk of hepatotoxicity, it may be a good option for individuals with AUD who have significant hepatic dysfunction.
Induction and maintenance: The initial dose of gabapentin is 300 mg once daily, with increases in increments of 300 mg every 1 to 2 days based on response and tolerability. The maintenance dose is individualized and generally divided into 3 doses per day. Based on studies of gabapentin for the treatment of other conditions (e.g., epilepsy, postherpetic neuralgia), maintenance doses up to 2,400 mg or 3,600 mg per day, divided into 3 doses, can be considered FDA 2017.
Adverse events: Common adverse events include headache, insomnia, fatigue, muscle aches, and gastrointestinal complaints. In clinical trials, these events were mild to moderate, did not result in drug discontinuation, and were not significantly different from adverse effects reported with placebo Mason, et al. 2018.
Clinicians can offer topiramate to patients with moderate-to-severe AUD (Diagnostic and Statistical Manual of Mental Disorders-5 criteria) who have a goal of reducing alcohol use or achieving abstinence. Abstinence from alcohol is not a requirement for initiating treatment.
Induction and maintenance doses: The initial dose of topiramate is 25 mg once daily, with increases in increments of 50 mg once every 7 days. The maintenance dose ranges from 200 mg to 400 mg daily, divided into 2 doses Knapp, et al. 2015; Kranzler, et al. 2014; Johnson, et al. 2003. In patients with moderate-to-severe renal impairment, a 50% dose reduction is advised Guerrini and Parmeggiani 2006; Perucca 1997.
Adverse events: Adverse effects that occurred in more than 10% of study subjects include paresthesia Swietach, et al. 2003; Spitzer, et al. 2002; Fujii, et al. 1993 and cognitive impairment Gomer, et al. 2007. These effects were mostly observed in the dose titration phase and often resolved with continued treatment. Rare adverse effects include increased rate of renal calculi (2- to 4-fold) Welch et al. 2006, oligohidrosis Ma, et al. 2007; Cerminara, et al. 2006, acute visual disturbances, and myopia and acute angle-closure glaucoma Shank and Maryanoff 2008.
|Abbreviations: AST/ALT, aspartate aminotransferase/alanine aminotransferase; CrCl, creatinine clearance; eGFR, estimated glomerular filtration rate.
|Table 1: Pharmacologic Treatment of Alcohol Use Disorder in Nonpregnant Adults [a]|
|Medication [b]||Dosage||Considerations for Use|
|Acamprosate oral (Campral)||Initial and maintenance: 666 mg 3 times per day.||
|Naltrexone oral (Revia)||Initial and maintenance: 50 mg once daily.
If adverse events occur, clinicians can consider a reduced dose of 25 mg once daily.
|XR Naltrexone, long-acting injectable (Vivitrol)||Initial: 50 mg oral naltrexone once daily for at least 3 days.
Maintenance: 380 mg intragluteal injection every 28 days.
|Disulfiram oral (Antabuse)||Initial and maintenance: 500 mg once daily for 1 to 2 weeks. Reduce to 250 mg once daily.||
|Gabapentin oral (multiple brands)||Initial: 300 mg once daily.
Titrate: Increase in increments of 300 mg.
Maintenance: Up to 3,600 mg daily, divided in 3 doses; dose is based on response and tolerance.
|Topiramate oral (multiple brands)||Initial: 25 mg once daily.
Titrate: Increase dose by 50 mg increments each week to a maximum of 400 mg daily administered in 2 divided doses.
Maintenance: 200 to 400 mg daily divided into 2 doses.
|ALL RECOMMENDATIONS: TREATMENT OF ALCOHOL USE DISORDER|
Choosing a Treatment Option
Managing Withdrawal Syndrome
Initiating Pharmacologic Treatment
Date of current publication: August 8, 2023
Lead authors: Jessica Rodrigues, MS; Jessica M. Atrio, MD, MSc; and Johanna L. Gribble, MA
Writing group: Steven M. Fine, MD, PhD; Rona M. Vail, MD; Samuel T. Merrick, MD; Asa E. Radix, MD, MPH, PhD; Christopher J. Hoffmann, MD, MPH; Charles J. Gonzalez, MD
Committee: Medical Care Criteria Committee
Date of original publication: August 8, 2023
Throughout its guidelines, the New York State Department of Health (NYSDOH) AIDS Institute (AI) Clinical Guidelines Program recommends “shared decision-making,” an individualized process central to patient-centered care. With shared decision-making, clinicians and patients engage in meaningful dialogue to arrive at an informed, collaborative decision about a patient’s health, care, and treatment planning. The approach to shared decision-making described here applies to recommendations included in all program guidelines. The included elements are drawn from a comprehensive review of multiple sources and similar attempts to define shared decision-making, including the Institute of Medicine’s original description [Institute of Medicine 2001]. For more information, a variety of informative resources and suggested readings are included at the end of the discussion.
The benefits to patients that have been associated with a shared decision-making approach include:
- Decreased anxiety [Niburski, et al. 2020; Stalnikowicz and Brezis 2020]
- Increased trust in clinicians [Acree, et al. 2020; Groot, et al. 2020; Stalnikowicz and Brezis 2020]
- Improved engagement in preventive care [McNulty, et al. 2022; Scalia, et al. 2022; Bertakis and Azari 2011]
- Improved treatment adherence, clinical outcomes, and satisfaction with care [Crawford, et al. 2021; Bertakis and Azari 2011; Robinson, et al. 2008]
- Increased knowledge, confidence, empowerment, and self-efficacy [Chen, et al. 2021; Coronado-Vázquez, et al. 2020; Niburski, et al. 2020]
Collaborative care: Shared decision-making is an approach to healthcare delivery that respects a patient’s autonomy in responding to a clinician’s recommendations and facilitates dynamic, personalized, and collaborative care. Through this process, a clinician engages a patient in an open and respectful dialogue to elicit the patient’s knowledge, experience, healthcare goals, daily routine, lifestyle, support system, cultural and personal identity, and attitudes toward behavior, treatment, and risk. With this information and the clinician’s clinical expertise, the patient and clinician can collaborate to identify, evaluate, and choose from among available healthcare options [Coulter and Collins 2011]. This process emphasizes the importance of a patient’s values, preferences, needs, social context, and lived experience in evaluating the known benefits, risks, and limitations of a clinician’s recommendations for screening, prevention, treatment, and follow-up. As a result, shared decision-making also respects a patient’s autonomy, agency, and capacity in defining and managing their healthcare goals. Building a clinician-patient relationship rooted in shared decision-making can help clinicians engage in productive discussions with patients whose decisions may not align with optimal health outcomes. Fostering open and honest dialogue to understand a patient’s motivations while suspending judgment to reduce harm and explore alternatives is particularly vital when a patient chooses to engage in practices that may exacerbate or complicate health conditions [Halperin, et al. 2007].
Options: Implicit in the shared decision-making process is the recognition that the “right” healthcare decisions are those made by informed patients and clinicians working toward patient-centered and defined healthcare goals. When multiple options are available, shared decision-making encourages thoughtful discussion of the potential benefits and potential harms of all options, which may include doing nothing or waiting. This approach also acknowledges that efficacy may not be the most important factor in a patient’s preferences and choices [Sewell, et al. 2021].
Clinician awareness: The collaborative process of shared decision-making is enhanced by a clinician’s ability to demonstrate empathic interest in the patient, avoid stigmatizing language, employ cultural humility, recognize systemic barriers to equitable outcomes, and practice strategies of self-awareness and mitigation against implicit personal biases [Parish, et al. 2019].
Caveats: It is important for clinicians to recognize and be sensitive to the inherent power and influence they maintain throughout their interactions with patients. A clinician’s identity and community affiliations may influence their ability to navigate the shared decision-making process and develop a therapeutic alliance with the patient and may affect the treatment plan [KFF 2023; Greenwood, et al. 2020]. Furthermore, institutional policy and regional legislation, such as requirements for parental consent for gender-affirming care for transgender people or insurance coverage for sexual health care, may infringe upon a patient’s ability to access preventive- or treatment-related care [Sewell, et al. 2021].
Health equity: Adapting a shared decision-making approach that supports diverse populations is necessary to achieve more equitable and inclusive health outcomes [Castaneda-Guarderas, et al. 2016]. For instance, clinicians may need to incorporate cultural- and community-specific considerations into discussions with women, gender-diverse individuals, and young people concerning their sexual behaviors, fertility intentions, and pregnancy or lactation status. Shared decision-making offers an opportunity to build trust among marginalized and disenfranchised communities by validating their symptoms, values, and lived experience. Furthermore, it can allow for improved consistency in patient screening and assessment of prevention options and treatment plans, which can reduce the influence of social constructs and implicit bias [Castaneda-Guarderas, et al. 2016].
Clinician bias has been associated with health disparities and can have profoundly negative effects [FitzGerald and Hurst 2017; Hall, et al. 2015]. It is often challenging for clinicians to recognize and set aside personal biases and to address biases with peers and colleagues. Consciously or unconsciously, negative or stigmatizing assumptions are often made about patient characteristics, such as race, ethnicity, gender, sexual orientation, mental health, and substance use [Avery, et al. 2019; van Boekel, et al. 2013; Livingston, et al. 2012]. With its emphasis on eliciting patient information, a shared decision-making approach encourages clinicians to inquire about patients’ lived experiences rather than making assumptions and to recognize the influence of that experience in healthcare decision-making.
Stigma: Stigma may prevent individuals from seeking or receiving treatment and harm reduction services [Tsai, et al. 2019]. Among people with HIV, stigma and medical mistrust remain significant barriers to healthcare utilization, HIV diagnosis, and medication adherence and can affect disease outcomes [Turan, et al. 2017; Chambers, et al. 2015], and stigma among clinicians against people who use substances has been well-documented [Stone, et al. 2021; Tsai, et al. 2019; van Boekel, et al. 2013]. Sexual and reproductive health, including strategies to prevent HIV transmission, acquisition, and progression, may be subject to stigma, bias, social influence, and violence.
|SHARED DECISION-MAKING IN HIV CARE|
Resources and Suggested Reading
In addition to the references cited below, the following resources and suggested reading may be useful to clinicians.
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Updates, Authorship, and Related Guidelines
|Updates, Authorship, and Related Guidelines|
|Date of original publication||July 2020|
|Intended users||All clinicians in New York State, including those who delivery primary care|
Yonina Mar, MD1; Hillary Kunins, MD
1Mount Sinai Beth Israel, New York, NY
Chinazo O. Cunningham, MD, MS; Kelly S. Ramsey, MD, MPH, MA, FACP; Sharon Stancliff, MD; Lyn C. Stevels, MS, NP, ACRN; Christopher J. Hoffmann, MD, MPH; Charles J. Gonzalez, MD
|Author and writing group conflict of interest disclosures||There are no author or writing group conflict of interest disclosures|
|Developer and funder|
See Guideline Development and Recommendation Ratings Scheme, below.
Guideline Development and Recommendation Ratings
|Guideline Development: New York State Department of Health AIDS Institute Clinical Guidelines Program|
|Program manager||Clinical Guidelines Program, Johns Hopkins University School of Medicine, Division of Infectious Diseases. See Program Leadership and Staff.|
|Mission||To produce and disseminate evidence-based, state-of-the-art clinical practice guidelines that establish uniform standards of care for practitioners who provide prevention or treatment of HIV, viral hepatitis, other sexually transmitted infections, and substance use disorders for adults throughout New York State in the wide array of settings in which those services are delivered.|
|Expert committees||The NYSDOH AI Medical Director invites and appoints committees of clinical and public health experts from throughout New York State to ensure that the guidelines are practical, immediately applicable, and meet the needs of care providers and stakeholders in all major regions of New York State, all relevant clinical practice settings, key New York State agencies, and community service organizations.|
|Disclosure and management of conflicts of interest||
|Evidence collection and review||
|Review and approval process||
|Recommendation Ratings Scheme|
|Strength||Quality of Evidence|
|A||Strong||1||Based on published results of at least 1 randomized clinical trial with clinical outcomes or validated laboratory endpoints.|
|B||Moderate||*||Based on either a self-evident conclusion; conclusive, published, in vitro data; or well-established practice that cannot be tested because ethics would preclude a clinical trial.|
|C||Optional||2||Based on published results of at least 1 well-designed, nonrandomized clinical trial or observational cohort study with long-term clinical outcomes.|
|2†||Extrapolated from published results of well-designed studies (including nonrandomized clinical trials) conducted in populations other than those specifically addressed by a recommendation. The source(s) of the extrapolated evidence and the rationale for the extrapolation are provided in the guideline text. One example would be results of studies conducted predominantly in a subpopulation (e.g., one gender) that the committee determines to be generalizable to the population under consideration in the guideline.|
|3||Based on committee expert opinion, with rationale provided in the guideline text.|