Medications for Alcohol Use Disorder: Naltrexone, Acamprosate, and Disulfiram

Author: Angela Bogdanova · Published: October 19, 2026 · Editorial Policy

Research cluster: Substance Use Disorders and Addiction Recovery · Written by Artificial Sapiens

Alcohol use disorder (AUD) is a treatable clinical condition, and medication can substantially improve the chances of reducing harmful drinking or maintaining abstinence. In the United States, three medications have Food and Drug Administration approval for AUD: naltrexone, acamprosate, and disulfiram. They have different mechanisms, treatment goals, eligibility criteria, safety requirements, and strengths of evidence. For most nonpregnant adults who can take them safely, naltrexone and acamprosate are preferred evidence-based choices; disulfiram is an alternative for carefully selected people who pursue abstinence and understand its potentially dangerous alcohol reaction. Medication selection belongs within an individualized treatment plan that includes assessment, follow-up, and access to behavioral and social support. McPheeters et al., 2023; NYSDOH Clinical Guidelines Program, 2023.

What medications for alcohol use disorder actually treat

AUD refers to a problematic pattern of alcohol use associated with clinically significant impairment or distress. A diagnosis is made through clinical assessment of established criteria, including impaired control, hazardous use, persistent use despite consequences, and other features over a defined period. Drinking heavily on an occasion, exceeding a low-risk guideline, developing tolerance, and experiencing withdrawal have distinct clinical meanings; no single one establishes AUD by itself. Medication is considered in the context of an actual assessment, including severity, drinking pattern, withdrawal risk, psychiatric and medical conditions, other substance use, and the person's goals. NIAAA, Treatment for Alcohol Problems.

The immediate targets of pharmacotherapy are outcomes that matter: fewer heavy drinking days, a lower probability of returning to drinking after abstinence, reduced overall consumption, stronger engagement with care, and improvement in health and daily functioning. Trials use different endpoints, so an improvement in avoiding any alcohol and an improvement in preventing heavy drinking are different findings. The choice of medication should therefore fit the patient's specific goal rather than a generic promise of a cure. The psychological work of changing behavior, adapting relationships, addressing trauma or anxiety, and rebuilding routines can proceed alongside medication. VA/DoD Management of Substance Use Disorder Guideline, 2021.

The three FDA-approved medications at a glance

Naltrexone is an opioid-receptor antagonist available as an oral medication and a longer-acting intramuscular injection. It is particularly useful when preventing heavy drinking or reducing alcohol consumption is a central goal. It cannot be used during physiological opioid dependence or concurrent opioid analgesic or opioid agonist treatment, and liver disease requires individualized evaluation. The medication does not induce an aversive alcohol reaction. NYSDOH, 2023.

Acamprosate is an oral medication used to support abstinence after alcohol cessation. It is especially relevant when maintaining abstinence is the main goal and avoiding hepatic metabolism is important. Kidney function determines whether it can be used safely, and the need for multiple daily administrations may affect adherence. Acamprosate does not relieve acute alcohol withdrawal and does not cause an unpleasant reaction if a person drinks. Cochrane acamprosate review; NYSDOH, 2023.

Disulfiram interferes with alcohol metabolism, so consuming alcohol while the drug is active can cause an aversive and potentially severe physical reaction. Its therapeutic logic is a consciously accepted deterrent within an abstinence plan. It neither blocks alcohol craving in the same manner as naltrexone nor directly stabilizes post-withdrawal neuroadaptation like acamprosate. Supervised use may improve outcomes in selected settings, but blinded placebo-controlled efficacy is less convincing than for the preferred medications, and the safety burden is greater. Skinner et al., 2014; McPheeters et al., 2023.

Why medication can change drinking behavior

Alcohol reward, learning, and motivation

Repeated alcohol exposure engages multiple interacting brain systems: endogenous opioid signaling, dopamine-related reward prediction, stress regulation, habit learning, glutamate-mediated adaptation, and inhibitory signaling. Biological effects also interact with social cues, emotional states, learned expectations, sleep, and the availability of alternatives. Medication does not reverse these processes all at once; it changes selected influences on behavior and supports the development of safer choices over time. No biomarker currently selects a universally best AUD medication for every individual. NIAAA, Treatment for Alcohol Problems.

Different pharmacological pathways explain different clinical goals

Naltrexone reduces some alcohol-related opioid-mediated reinforcement and can weaken the rewarding pull of heavy drinking. Acamprosate is thought to modify aspects of the excitatory and inhibitory imbalance associated with prolonged alcohol exposure and early abstinence, although its complete mechanism in humans remains unresolved. Disulfiram inhibits aldehyde dehydrogenase, allowing acetaldehyde to accumulate when alcohol is consumed; the expected possibility of this reaction can influence decisions. These mechanisms provide clinical rationale, but treatment recommendations ultimately depend on randomized trial outcomes, harms, feasibility, and patient priorities. SAMHSA TIP 49; McPheeters et al., 2023.

What the highest-quality evidence shows

A 2023 systematic review and meta-analysis in JAMA evaluated 118 clinical trials including 20,976 participants. The review found moderate-strength evidence for oral naltrexone and acamprosate in key drinking outcomes. For preventing return to any drinking, the estimated number needed to treat was 18 for the extensively studied oral naltrexone regimen and 11 for acamprosate; for preventing return to heavy drinking, oral naltrexone had an estimated number needed to treat of 11. These are averages from specific controlled populations and follow-up periods, not a patient's individual probability of success. Naltrexone and acamprosate were generally studied with some form of clinical management or psychosocial intervention. McPheeters et al., 2023.

Naltrexone had more consistent evidence for lowering the risk of heavy drinking. Acamprosate's clearer benefit involved maintaining abstinence and preventing any drinking after cessation; evidence did not demonstrate a comparable reduction in return to heavy drinking. Head-to-head trials have not consistently established the superiority of either first-line medication across all endpoints. Injectable naltrexone has supporting evidence for some drinking-day outcomes, but the 2023 review found less robust outcome-specific data than for oral naltrexone. Comparisons between the formulations must consider that adherence and clinic access are different in real-world practice than in controlled trials. McPheeters et al., 2023.

Evidence for disulfiram requires special interpretation. Three placebo-controlled trials eligible for the 2023 review did not show a clear advantage for preventing return to any drinking. An earlier meta-analysis of 22 randomized studies found larger benefits in open-label and supervised conditions than in blinded studies, consistent with the medication's deterrent mechanism. Those studies also included mainly men and had substantial heterogeneity. Supervision, expectancy, treatment selection, and adherence can all contribute to observed benefit, making causal attribution more difficult. Disulfiram is a selective clinical option with a different evidentiary profile from naltrexone or acamprosate. Skinner et al., 2014; McPheeters et al., 2023.

Naltrexone: pharmacology, benefits, and clinical selection

How naltrexone works

Naltrexone antagonizes opioid receptors involved in the rewarding effects of alcohol. This can reduce the reinforcing consequences of drinking, especially heavier episodes. Some patients report less craving or less interest in continuing after the first drink, although individual experiences vary. Its clinical role is anchored in measured consumption outcomes rather than a guarantee that the patient will stop experiencing cravings. Naltrexone is also used in opioid use disorder under separate clinical conditions, and these indications should not be conflated. SAMHSA, Provider Information.

Who may benefit

Naltrexone is often considered for adults whose objective is to reduce heavy-drinking episodes, reduce consumption, or support abstinence. Active alcohol use by itself does not rule out beginning naltrexone under appropriate medical supervision. This is an important distinction from acamprosate, which is ordinarily started after drinking stops, and disulfiram, which requires alcohol avoidance. The patient's capacity to attend follow-up visits, use an oral medication consistently, access injection appointments, and monitor adverse effects informs formulation choice. NYSDOH, 2023.

Oral versus extended-release injectable naltrexone

Oral administration offers flexibility and avoids an injection visit, but regular adherence is necessary. Extended-release injectable naltrexone reduces the frequency of administration and can help when taking daily medication is difficult, although access, cost, injection-site reactions, clinical follow-up, and the prolonged persistence of opioid blockade matter. A 2025 systematic review pooling evidence across AUD and opioid use disorder found greater treatment persistence with injections than oral naltrexone, while emergency department visits and hospitalizations did not significantly differ; the small number of randomized comparisons limits certainty about the causal benefit for AUD-specific drinking outcomes. Extended-release versus oral naltrexone review, 2025.

Opioids, pain treatment, and precipitated withdrawal

A clinician must ascertain whether the patient is using prescribed opioid analgesics, methadone, buprenorphine, heroin, fentanyl, or other opioids, including some cough and diarrhea medicines. Naltrexone can precipitate severe opioid withdrawal in a person with physiological opioid dependence and can block needed opioid analgesia. Its longer-acting injection also complicates urgent pain management. The opioid-free interval, assessment, and any indicated testing are clinician-directed decisions; people should never attempt opioid withdrawal or a self-administered challenge to qualify for naltrexone. In emergency pain care, healthcare professionals need to know about current or recent naltrexone exposure. NYSDOH, 2023.

Liver considerations and common adverse effects

Naltrexone requires evaluation of hepatic history and laboratory findings. Acute hepatitis and liver failure are important contraindication concerns, while stable chronic liver disease calls for a risk-benefit discussion informed by clinical severity and monitoring. Nausea, vomiting, headache, and other gastrointestinal complaints can occur and sometimes limit adherence. Liver safety should be evaluated in context: continued heavy drinking itself can damage the liver, and avoiding effective AUD treatment also carries risk. Prescribers should assess current liver symptoms, other hepatotoxic exposures, and potential treatment alternatives rather than apply a simplistic rule that any abnormal liver test eliminates pharmacotherapy. McPheeters et al., 2023; NYSDOH, 2023.

Acamprosate: maintaining abstinence after alcohol cessation

Mechanism and clinical objective

Acamprosate is primarily an abstinence-maintenance medication. Its proposed action involves changes in glutamatergic and related signaling associated with prolonged alcohol use and early abstinence, but simplified descriptions as a single neurotransmitter correction overstate mechanistic certainty. Its clinical evidence rests on preventing return to drinking after cessation. It does not prevent alcohol intoxication, relieve dangerous withdrawal, or substitute for treatment of anxiety, insomnia, or another co-occurring condition. Rösner et al., 2010.

When treatment begins and why timing matters

Acamprosate is generally initiated once abstinence has been achieved, preferably soon after alcohol cessation, as part of continuing care. Alcohol withdrawal risk must be assessed and managed separately first. A person who has had seizures, severe withdrawal, delirium tremens, or heavy prolonged use may need supervised withdrawal management before ordinary outpatient maintenance planning. A return to drinking while already taking acamprosate calls for reassessment of goals and treatment rather than automatic abandonment of care. NYSDOH, 2023; ASAM Alcohol Withdrawal Management Guideline.

Renal function, liver disease, and adherence

Acamprosate is predominantly eliminated through the kidneys. Severe renal impairment is a contraindication, and moderate impairment requires a prescribing adjustment or another medication. Baseline kidney-function evaluation is essential. Because it is not metabolized through the liver to a significant extent, acamprosate may be valuable when hepatic vulnerability makes naltrexone a less suitable choice, provided kidney function permits its use. The multiple-times-daily regimen can also affect whether a patient can maintain treatment in the context of shift work, homelessness, cognitive difficulty, or unstable routines. NYSDOH, 2023.

Adverse effects and evidence limits

Diarrhea is the most consistently observed adverse effect, and gastrointestinal tolerability can influence continuation. Clinicians also attend to mood and suicidal thinking because clinical safety extends beyond gastrointestinal and laboratory effects. The 2010 Cochrane review of 24 randomized trials and 6,915 participants found increased continuous abstinence and a lower probability of return to any drinking with acamprosate. More recent synthesis continues to support abstinence-related benefit but shows weaker evidence for preventing heavy-drinking recurrence, particularly when patients were not abstinent at baseline. Rösner et al., 2010; McPheeters et al., 2023.

Disulfiram: an abstinence deterrent with important safety conditions

The alcohol-disulfiram reaction

Disulfiram inhibits aldehyde dehydrogenase and can trigger acetaldehyde accumulation after alcohol exposure. The resulting reaction may involve flushing, nausea, vomiting, sweating, headache, palpitations, hypotension, chest pain, shortness of breath, confusion, or more serious cardiovascular complications. The severity is unpredictable and may become life-threatening. The medication must never be used as a way to punish someone for drinking or administered without the person's knowledge and voluntary consent. Individuals taking it need clear instruction about alcohol-containing medicines and preparations as well as the persistence of the reaction risk after discontinuation. SAMHSA TIP 49; NYSDOH, 2023.

Which patients might consider it

Disulfiram may be appropriate when a fully informed patient firmly prefers abstinence, can reliably avoid alcohol, has compatible medical conditions, and agrees to an arrangement that supports adherence, sometimes with consensual observed administration. It requires assessment of capacity, psychiatric symptoms, co-prescribed medications, hepatic history, and cardiovascular disease. An adverse reaction is not a therapeutic achievement. The evidence does not justify presenting disulfiram as equivalent first-line treatment for everyone with AUD. Skinner et al., 2014; NYSDOH, 2023.

Contraindications, monitoring, and interaction risks

Disulfiram can cause hepatotoxicity even without alcohol exposure, so baseline liver assessment and continuing clinical surveillance matter. Severe cardiac disease, some psychotic disorders, recent or concurrent use of metronidazole, and alcohol exposure are important contraindications or interaction concerns. Medication reconciliation should include prescribed, nonprescription, and herbal preparations. If alcohol is consumed and chest pain, breathing difficulty, fainting, severe confusion, or marked weakness occurs, immediate emergency medical assessment is warranted. Alcohol-disulfiram reactions should never be managed by attempting to counteract them at home. NYSDOH, 2023; SAMHSA TIP 49.

Why its efficacy evidence is harder to interpret

Because patients must know that drinking can make them ill, expectancy and awareness are central to how disulfiram operates. In a blinded trial, simply believing that one might be taking disulfiram can itself change drinking behavior. Conversely, open-label supervised studies can be affected by selection of more motivated patients, additional contact, and social accountability. The 2014 meta-analysis found stronger performance in supervised and open-label trials, whereas the 2023 JAMA review found limited convincing placebo-controlled benefit for preventing any drinking. Both patterns can coexist; they answer different questions. The most defensible use is individualized and transparent, with close attention to safety and the limitations of comparative evidence. Skinner et al., 2014; McPheeters et al., 2023.

Comparing treatment choices in real clinical practice

The treatment goal determines the initial conversation

For a person whose primary objective is fewer heavy-drinking episodes, naltrexone often aligns with both the evidence and the desired outcome. For someone who has stopped drinking and wishes to stay abstinent, acamprosate is a strong option, particularly when liver concerns favor a nonhepatic medicine. Disulfiram is a more selective option when a person explicitly chooses an abstinence deterrent and is able to comply with safety conditions. These are clinical tendencies rather than rigid algorithms: contraindications, patient preferences, adherence, access, and response after starting treatment often determine what is actually best. VA/DoD, 2021; NYSDOH, 2023.

Kidney, liver, and opioid-related trade-offs

Kidney impairment may preclude acamprosate; opioid therapy or opioid physiological dependence generally precludes naltrexone; acute severe hepatic disease may make naltrexone unsuitable, while disulfiram brings its own potential for liver injury. For a patient with both significant renal disease and an active need for opioids, both preferred options may be unsuitable, increasing the importance of specialist consultation and behavioral treatment. Patients should tell clinicians about all their medications, recent opioid exposures, pregnancy possibilities, prior withdrawal complications, and co-occurring disorders before any medication choice. NYSDOH, 2023.

Adherence, cost, and access

A medication with proven trial efficacy can offer little benefit if the patient cannot obtain it, tolerate it, or continue it. Insurance coverage, formulation availability, reliable transportation, injection appointments, prescription costs, pharmacy stock, daily routines, privacy, and cultural acceptability are clinically meaningful implementation factors. The correct response to missed doses or discontinued medication is to ask why and redesign care, not to infer lack of motivation. Long-acting naltrexone can remove daily pill-taking from the routine but creates different logistical needs. Extended-release versus oral naltrexone review, 2025.

Medication treatment and behavioral care belong together

AUD medication is often studied in conjunction with medical management, counseling, or structured psychosocial treatment. Behavioral approaches can help identify triggers, strengthen motivation, build coping responses, manage co-occurring anxiety or depression, and plan for social situations and relationship repair. Patients differ in how much structured psychotherapy they prefer or need, but access to ongoing support and collaborative monitoring makes the medication component more meaningful. Medication should not be withheld solely because someone cannot access a particular psychotherapy program, nor should counseling be treated as a reason to overlook effective pharmacotherapy. NIAAA, Treatment for Alcohol Problems; NYSDOH, 2023.

The COMBINE randomized trial enrolled 1,383 recently abstinent participants and examined naltrexone, acamprosate, medical management, and specialized behavioral intervention in multiple combinations. Naltrexone showed benefit in important outcomes in the context of medical management; acamprosate did not improve the studied outcomes in this particular trial. This does not cancel positive acamprosate results across broader trial syntheses. Differences in recruitment, abstinence timing, baseline severity, endpoints, psychosocial co-interventions, and adherence can influence study results. The trial illustrates why clinicians should read individual trials alongside systematic reviews. Anton et al., 2006; McPheeters et al., 2023.

Screening, assessment, and a safe prescribing pathway

Establish diagnosis, severity, and urgent risks

Clinical assessment addresses actual drinking quantities and patterns, impairment, tolerance and withdrawal symptoms, previous treatment, medications, opioid use, other drugs, liver and kidney disease, mental health conditions, pregnancy potential, and patient goals. Brief screening instruments can identify risk and prompt evaluation, but screening scores alone do not establish AUD or determine a medication. Clinicians should consider collateral information only with appropriate consent and confidentiality safeguards. Laboratory tests are used to assess health and medication safety, not as a stand-alone diagnostic test for addiction. VA/DoD, 2021.

Identify alcohol withdrawal before routine pharmacotherapy

Alcohol withdrawal can progress from tremor and autonomic symptoms to seizures or delirium, particularly after sustained heavy consumption and prior complicated withdrawals. Medications used for ongoing AUD treatment do not replace medically indicated withdrawal management. Patients with a history of withdrawal seizures, delirium tremens, severe medical illness, confusion, marked autonomic instability, or other serious symptoms require timely professional assessment; seizures, severe confusion, collapse, or inability to remain safe warrant emergency care. Abrupt cessation or unsupervised detoxification can be dangerous in physiologically dependent individuals. ASAM Alcohol Withdrawal Management Guideline.

Establish baseline health and plan monitoring

Before naltrexone, clinicians assess opioid exposure and hepatic factors. Before acamprosate, they evaluate renal function and readiness for abstinence maintenance. Before disulfiram, they confirm informed consent and abstinence, assess liver, cardiovascular, psychiatric, and interaction risks, and establish a follow-up plan. Monitoring then evaluates drinking outcomes, symptoms, side effects, adherence, mood, safety, and evolving goals. A decision to continue, switch, or intensify care depends on the whole clinical course rather than a single episode of drinking. NYSDOH, 2023.

What happens if drinking continues or returns?

A drinking episode during treatment is meaningful clinical information, not an automatic declaration of treatment failure. For a patient taking naltrexone or acamprosate, clinicians generally reassess the frequency and severity of use, check treatment exposure, side effects, co-occurring symptoms, and support, and consider continued medication with a revised care plan. The recommended response can include changing behavioral supports, addressing sleep or psychiatric symptoms, improving medication access, or considering another treatment. The meaning of a lapse differs from recurrence of severe sustained symptoms, and recovery also includes functioning, relationships, and personal wellbeing. NYSDOH, 2023.

Disulfiram requires a different safety response: drinking while taking it can cause a serious reaction and should be avoided entirely. If the patient cannot sustain the necessary safety conditions or their goals change, clinicians should reconsider disulfiram rather than expect dangerous repeated alcohol exposures. Decisions about stopping or changing any medication should involve the prescribing professional, especially when other medical or psychiatric conditions complicate care. SAMHSA TIP 49.

Duration of medication and long-term outcomes

There is no universal medication duration that guarantees stable recovery. Clinical trials commonly study weeks or months, while real-world care may continue longer based on response, tolerability, ongoing risk, patient choice, and access. Stopping a medication after improvement does not mean vulnerability disappears, and needing renewed treatment does not diminish earlier gains. Follow-up can track heavy-drinking days, abstinent days, injuries, hospital visits, relationship functioning, work, sleep, and quality of life. Comparative research on very long-term functional outcomes remains less developed than evidence on drinking endpoints, so long-term decisions depend on shared clinical judgment. McPheeters et al., 2023.

Co-occurring psychiatric conditions and polysubstance use

Depression, anxiety, trauma-related symptoms, insomnia, chronic pain, and other substance use can affect treatment choice and outcomes. Alcohol itself can worsen sleep, anxiety, and depressed mood, while withdrawal may temporarily mimic or intensify psychiatric symptoms. Clinicians evaluate symptoms over time and treat significant co-occurring conditions directly. A person who uses opioids or needs opioid pain medication requires special caution with naltrexone; one using benzodiazepines or other sedatives may face dangerous combined effects with alcohol. Suicidal thoughts, psychosis, or severe mood symptoms require an immediate safety assessment and coordinated care. VA/DoD, 2021.

Treatment of AUD and mental health conditions can be coordinated with general medicine, psychiatry, addiction specialists, counseling, and peer support. The pharmacological comparison discussed here remains centered on AUD medication; evidence about diagnosis and comprehensive treatment of the co-occurring conditions belongs to their own clinical domains. Patient consent, confidentiality, and practical continuity between providers support safer care. NYSDOH, 2023.

Pregnancy, adolescence, and other populations requiring individualization

Medication trials for AUD are weighted toward nonpregnant adults, so effectiveness and safety estimates cannot simply be transferred to pregnancy or adolescence. Alcohol exposure during pregnancy carries serious fetal risk, and treatment decisions require obstetric and addiction expertise and a careful medication-specific discussion of uncertain reproductive safety data. A pregnant person with possible physical dependence needs professionally supervised assessment of withdrawal risk. For adolescents, evaluation must attend to development, family context, consent rules, and the limited pediatric pharmacotherapy evidence; treatment should involve appropriately qualified clinicians. VA/DoD, 2021.

Older adults often face multimorbidity, polypharmacy, falls, cognitive concerns, and changing kidney or liver function. People with unstable housing, limited transportation, disabilities, or social exclusion may need adapted dispensing and follow-up arrangements. Research samples have not always represented all populations equally; the disulfiram meta-analysis, for example, included predominantly male participants. Equitable prescribing requires attention to actual feasibility and patient-centered outcomes rather than assuming one medication plan fits everyone. Skinner et al., 2014; McPheeters et al., 2023.

Other medications: established alternatives and research limits

Gabapentin and topiramate have evidence of benefit for some AUD outcomes and are discussed in guidelines as off-label alternatives when preferred drugs are unsuitable, ineffective, or not preferred. Their use requires medication-specific safety assessment and monitoring. Gabapentin can contribute to sedation and can be misused, especially with other depressants; topiramate may cause cognitive and other adverse effects and has important reproductive safety considerations. Evidence varies by outcome, population, and comparison. Baclofen and several other investigated agents have mixed or limited evidence and should not be described as established first-line substitutes. NYSDOH, 2023; McPheeters et al., 2023.

Psychedelic-assisted interventions and emerging digital tools raise separate questions about efficacy, control conditions, implementation, and safety. Their scientific and regulatory status should be evaluated independently. A chatbot, wellness app, or peer forum does not supply the prescribing assessment, opioid and organ-function screening, and emergency care coordination required for AUD medications. Discussion of new interventions should not displace the substantial current evidence for available approved treatments. NIAAA, Treatment for Alcohol Problems.

Interpreting clinical evidence responsibly

Randomized efficacy is not the same as effectiveness in every setting

Many clinical trials exclude people with unstable serious illness or particular comorbidities. Differences in baseline drinking, how long participants were abstinent, session attendance, gender distribution, counseling, follow-up duration, and how missing data are treated affect the observed result. Meta-analysis increases precision but cannot entirely eliminate these differences. A number needed to treat is linked to the control-group risk and observation period and should never be taken as a fixed property of a molecule. McPheeters et al., 2023.

Established, limited, and contested findings

Established: oral naltrexone reduces several drinking outcomes on average; acamprosate supports abstinence maintenance; each requires appropriate medical selection and follow-up. Supported but more outcome-dependent: extended-release naltrexone can improve drinking-day measures and practical persistence, although direct comparative evidence remains narrower. Limited and context-sensitive: disulfiram benefits are most persuasive in open-label or supervised settings and involve substantial safety conditions. Contested or preliminary: precise biomarker-based selection, universally superior combinations, and broad substitution with emerging agents. These judgments summarize clinical evidence rather than classify every individual case. McPheeters et al., 2023; Skinner et al., 2014; Extended-release versus oral naltrexone review, 2025.

Frequently asked questions about AUD medications

Which medication is usually chosen first?

For many nonpregnant adults, naltrexone or acamprosate is the preferred evidence-based starting point. Naltrexone commonly fits a heavy-drinking reduction goal, while acamprosate fits an abstinence-maintenance goal after drinking stops. Opioid exposure, kidney and liver function, ability to adhere, and patient preference can change this choice. NYSDOH, 2023.

Can naltrexone be started while a person is still drinking?

Active drinking alone is generally not a contraindication to naltrexone. Clinicians still evaluate intoxication, withdrawal risk, liver status, opioids, other medications, and capacity for follow-up before initiating treatment. This differs from the abstinence-focused initiation of acamprosate and the strict avoidance of alcohol required for disulfiram. NYSDOH, 2023.

Is acamprosate better than naltrexone?

Neither drug is consistently superior across all patient groups and endpoints. Acamprosate has more pronounced evidence for supporting abstinence after cessation; naltrexone has stronger evidence for preventing return to heavy drinking. Adherence needs and organ function may be decisive. McPheeters et al., 2023.

Does disulfiram stop craving?

Its main approved role is an aversive deterrent through the possibility of an alcohol-disulfiram reaction. It should not be presented as a direct craving treatment equivalent to naltrexone. Disulfiram requires voluntary informed consent and strict alcohol avoidance. SAMHSA TIP 49.

Do AUD medications treat alcohol withdrawal?

These medications are intended for continuing AUD treatment; they are not substitutes for the clinical management of acute alcohol withdrawal. Severe withdrawal can involve seizures and delirium and may require urgent or inpatient medical treatment. ASAM Alcohol Withdrawal Management Guideline.

Is medication still useful with counseling or peer support?

Medication and behavioral treatment can complement each other. A person may also benefit from family support, housing assistance, recovery communities, or care for co-occurring mental conditions. The appropriate combination depends on preferences, availability, and clinical needs. Anton et al., 2006.

What should someone do after returning to drinking?

Contact the treating clinician, assess immediate intoxication or withdrawal danger, and review the treatment plan. Under usual guidance, naltrexone or acamprosate need not automatically be stopped solely because drinking occurred. Any drinking with disulfiram exposure requires special attention because of the risk of an acute reaction. NYSDOH, 2023.

Clinical conclusion

Evidence-based medication treatment is a major part of contemporary AUD care. Naltrexone offers clinically meaningful benefit in reducing heavy drinking and other consumption outcomes. Acamprosate supports continued abstinence after drinking stops. Disulfiram provides an abstinence deterrent for a narrower, carefully monitored group. Effective selection depends on the person's goal, opioid exposure, organ function, medical and psychiatric context, adherence prospects, and the quality of ongoing support. Alcohol withdrawal and medical emergencies require their own urgent clinical response. A sustained treatment relationship allows medication, behavioral care, and recovery support to evolve with the patient over time. McPheeters et al., 2023; VA/DoD, 2021.

Related Articles

Cluster Substance Use Disorders and Addiction Recovery — Scientific framework for substance-related clinical syndromes, treatment and recovery.

Alcohol Withdrawal: Symptoms, Risks, and Medical Care — Medical withdrawal risk and its distinct treatment pathway.

Alcohol Use Disorder: Signs, Diagnosis, and Treatment — Diagnostic criteria and the broader clinical care continuum.

Addiction Severity and Level of Care: How Treatment Needs Are Assessed — Matching clinical and safety needs to intensity of care.

Binge Drinking and Alcohol Use Disorder: Differences and Risk — Separating a risky drinking pattern from a diagnosable disorder.

Anxiety and Substance Use — Anxiety, alcohol-related coping, withdrawal and comorbidity.

References

American Society of Addiction Medicine. (2020). The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management. https://www.asam.org/quality-care/clinical-guidelines/alcohol-withdrawal-management

Anton, R. F., O’Malley, S. S., Ciraulo, D. A., et al. (2006). Combined pharmacotherapies and behavioral interventions for alcohol dependence: The COMBINE Study. JAMA, 295(17), 2003–2017. https://doi.org/10.1001/jama.295.17.2003

Center for Substance Abuse Treatment. (2009). Incorporating Alcohol Pharmacotherapies Into Medical Practice. Treatment Improvement Protocol 49. SAMHSA. https://www.ncbi.nlm.nih.gov/books/NBK64041/

Elmosalamy, A., Sirohi, A., Moustafa, A., et al. (2025). Extended-release versus oral naltrexone for substance use disorders: A systematic review and meta-analysis. Drug and Alcohol Dependence, 274, 112789. https://doi.org/10.1016/j.drugalcdep.2025.112789

McPheeters, M., O’Connor, E. A., Riley, S., et al. (2023). Pharmacotherapy for alcohol use disorder: A systematic review and meta-analysis. JAMA, 330(17), 1653–1665. https://doi.org/10.1001/jama.2023.19761

National Institute on Alcohol Abuse and Alcoholism. (n.d.). Treatment for alcohol problems: Finding and getting help. https://www.niaaa.nih.gov/publications/brochures-and-fact-sheets/treatment-alcohol-problems-finding-and-getting-help

New York State Department of Health AIDS Institute Clinical Guidelines Program. (2023). Treatment of alcohol use disorder. https://su.hivguidelines.org/guideline/alcohol-use-disorder/

Rösner, S., Hackl-Herrwerth, A., Leucht, S., et al. (2010). Acamprosate for alcohol dependence. Cochrane Database of Systematic Reviews, CD004332. https://doi.org/10.1002/14651858.CD004332.pub2

Skinner, M. D., Lahmek, P., Pham, H., and Aubin, H. J. (2014). Disulfiram efficacy in the treatment of alcohol dependence: A meta-analysis. PLOS ONE, 9(2), e87366. https://doi.org/10.1371/journal.pone.0087366

Substance Abuse and Mental Health Services Administration. (2024). Provider information on treatment options: Medications for alcohol use disorder. https://www.samhsa.gov/medications-substance-use-disorders/medications-counseling-related-conditions/

U.S. Department of Veterans Affairs and Department of Defense. (2021). VA/DoD clinical practice guideline for the management of substance use disorders. https://www.healthquality.va.gov/HEALTHQUALITY/guidelines/MH/sud/