Naltrexone and Acamprosate for Alcohol Use Disorder: How They Work, Effectiveness, and What to Expect

Naltrexone and acamprosate are two FDA-approved medications used in the treatment of alcohol use disorder (AUD) — a chronic, relapsing condition characterized by an impaired ability to stop or control alcohol use despite adverse consequences. According to the DSM-5-TR, alcohol use disorder is diagnosed on a spectrum from mild to severe based on the number of diagnostic criteria met within a 12-month period.

These medications belong to a broader treatment approach known as medication-assisted treatment (MAT) or, more recently, medications for alcohol use disorder (MAUD). Unlike disulfiram (Antabuse), which works by creating an aversive reaction to alcohol, naltrexone and acamprosate work through distinct neurobiological mechanisms to reduce cravings, diminish the rewarding effects of alcohol, or restore neurochemical balance disrupted by chronic drinking.

It is important to understand that these medications are not "cures" for alcohol use disorder. They are clinical tools designed to be used alongside psychosocial interventions — including therapy, support groups, and lifestyle changes — to support sustained recovery. Neither medication is addictive, and both have well-established safety profiles when used as prescribed.

Naltrexone is an opioid receptor antagonist, meaning it blocks opioid receptors in the brain — specifically the mu-opioid receptor. When a person drinks alcohol, the brain releases endogenous opioids (endorphins), which bind to these receptors and produce feelings of pleasure and reward. By blocking these receptors, naltrexone reduces the pleasurable and reinforcing effects of alcohol. Over time, this blunts the association between drinking and reward, which helps reduce cravings and makes it easier to cut back or abstain.

Naltrexone is available in two forms:

• Oral naltrexone (ReVia, generic) — A 50 mg tablet taken once daily
• Extended-release injectable naltrexone (Vivitrol) — A 380 mg intramuscular injection administered once monthly by a healthcare provider

Acamprosate (Campral) works through a different mechanism. Chronic alcohol use disrupts the balance between excitatory and inhibitory neurotransmitter systems in the brain — specifically the glutamate (excitatory) and GABA (inhibitory) systems. When a person with AUD stops drinking, the brain enters a state of neuronal hyperexcitability, which manifests as anxiety, insomnia, restlessness, and dysphoria — symptoms that powerfully drive relapse.

Acamprosate is thought to modulate glutamatergic neurotransmission, particularly by interacting with NMDA receptors and possibly metabotropic glutamate receptors, thereby restoring a more normal neurochemical balance. This helps reduce the protracted withdrawal symptoms and negative emotional states that persist long after acute detoxification. Acamprosate is taken as two 333 mg tablets three times daily, for a total daily dose of 1,998 mg.

In summary: naltrexone primarily reduces the reward of drinking, while acamprosate primarily eases the discomfort of not drinking. These complementary mechanisms mean that the choice between them — or the decision to use both — depends on the individual's clinical presentation and treatment goals.

Both naltrexone and acamprosate are specifically indicated for the treatment of alcohol use disorder in adults. However, their optimal use differs based on clinical context:

• Naltrexone is appropriate for individuals who are still drinking and want to reduce consumption, as well as those who have recently achieved abstinence and want to maintain it. It can be initiated while a person is still drinking, which makes it accessible for individuals who are not yet ready for or have not completed detoxification. Naltrexone is also FDA-approved for opioid use disorder prevention of relapse, making it a consideration for individuals with co-occurring alcohol and opioid use concerns.
• Acamprosate is indicated for individuals who have already achieved initial abstinence and want to maintain it. It is typically started after detoxification is complete — generally five or more days after the last drink. Acamprosate does not treat acute withdrawal symptoms and should not be used as a substitute for medically managed detoxification.

Certain populations require special consideration:

• Individuals with liver disease: Naltrexone is hepatically metabolized, and while it is generally well-tolerated, it carries a boxed warning regarding hepatotoxicity at high doses. Liver function should be assessed before and during treatment. Acamprosate, which is renally excreted without hepatic metabolism, is the preferred choice for patients with significant liver impairment.
• Individuals with kidney disease: Acamprosate is contraindicated in patients with severe renal impairment (creatinine clearance ≤30 mL/min) and requires dose adjustment in moderate impairment. Naltrexone is the better option for these patients.
• Individuals on opioid medications: Naltrexone is absolutely contraindicated in individuals currently using opioids or opioid agonist therapies (such as methadone or buprenorphine), as it can precipitate acute opioid withdrawal. A period of 7–14 days opioid-free is typically required before initiating naltrexone.
• Co-occurring psychiatric conditions: Both medications are generally safe for individuals with co-occurring depression, anxiety, or other psychiatric conditions. However, comprehensive psychiatric assessment is essential, as AUD frequently co-occurs with mood disorders, anxiety disorders, PTSD, and personality disorders.

Beginning treatment with naltrexone or acamprosate involves a structured clinical process. Here is what patients can generally expect:

Initial assessment: A healthcare provider will conduct a comprehensive evaluation including medical history, drinking patterns, prior treatment attempts, liver and kidney function tests, and assessment for co-occurring mental health and substance use conditions. If naltrexone is being considered, a urine drug screen is typically performed to confirm the absence of opioids.

Starting naltrexone: Oral naltrexone is usually started at 25 mg for the first one to two days to assess tolerability, then increased to the standard 50 mg daily dose. Some providers initiate treatment at the full dose. For injectable naltrexone (Vivitrol), patients must be opioid-free for a minimum of 7–14 days. The injection is given in the gluteal muscle by a healthcare professional every four weeks. Many patients report that the reduction in cravings and the diminished pleasure from alcohol are noticeable within the first few days to weeks.

Starting acamprosate: Acamprosate is initiated after abstinence has been achieved, typically once acute withdrawal has resolved. The standard regimen is two 333 mg tablets taken three times daily — a regimen that can be challenging to maintain due to the pill burden. The therapeutic effects of acamprosate develop gradually, and patients may not notice an immediate change. Consistent daily use is essential for effectiveness.

Duration of treatment: Clinical guidelines from the American Psychiatric Association and SAMHSA recommend a minimum treatment duration of three to twelve months, with many experts advocating for longer-term use — particularly for individuals with severe AUD or multiple prior relapses. The decision to discontinue medication should be made collaboratively between patient and provider, taking into account the stability of recovery and ongoing risk factors.

Psychosocial treatment: Medication alone is rarely sufficient. Both naltrexone and acamprosate achieve their best outcomes when combined with evidence-based psychosocial interventions such as cognitive-behavioral therapy (CBT), motivational enhancement therapy (MET), 12-step facilitation, or other structured support programs. The medication creates a neurobiological foundation that makes it easier to engage in and benefit from these therapeutic approaches.

Monitoring: Regular follow-up appointments — typically monthly initially, then quarterly — are important for monitoring medication adherence, side effects, liver or kidney function, and overall progress in recovery. Open communication with the prescribing provider about any alcohol use, cravings, or side effects is critical.

Both naltrexone and acamprosate have robust evidence bases, supported by large-scale randomized controlled trials, systematic reviews, and meta-analyses.

Naltrexone: The landmark COMBINE study (2006), one of the largest clinical trials for AUD treatment, found that oral naltrexone combined with medical management was effective in reducing heavy drinking days and increasing the percentage of abstinent days. A Cochrane systematic review encompassing over 7,000 participants across 50 randomized controlled trials concluded that naltrexone reduces the risk of heavy drinking by approximately 17% compared to placebo, and reduces drinking days by about 4%. The number needed to treat (NNT) to prevent one person from returning to heavy drinking is approximately 12.

Injectable naltrexone (Vivitrol) has demonstrated particular benefits in terms of medication adherence. The pivotal trial by Garner et al. (2005) showed significant reductions in heavy drinking days compared to placebo, especially among individuals who were abstinent at treatment initiation.

Acamprosate: A large European evidence base supports acamprosate's efficacy in maintaining abstinence. A meta-analysis by Rösner et al. (2010) published in the Cochrane Database, which included 24 randomized controlled trials with over 6,900 participants, found that acamprosate significantly increased the cumulative duration of abstinence compared to placebo. The NNT to prevent one relapse to any drinking is approximately 12. Notably, European trials have generally shown stronger effects than the U.S.-based COMBINE study, which did not find a significant benefit for acamprosate. This discrepancy may be related to differences in study populations, treatment goals (abstinence vs. reduced drinking), and concurrent psychosocial interventions.

Comparative effectiveness: The Agency for Healthcare Research and Quality (AHRQ) conducted a comprehensive systematic review in 2014, concluding that both naltrexone and acamprosate are supported by strong evidence for treating AUD, though they work best for different treatment goals. Naltrexone appears more effective for reducing heavy drinking, while acamprosate appears more effective for maintaining abstinence in those who have already stopped drinking. There is limited evidence that combining the two medications produces superior outcomes compared to either alone, though this remains an area of ongoing research.

It is important to set realistic expectations. These medications are not magic bullets. Research consistently shows that they work best as part of a comprehensive treatment plan, and individual responses vary considerably. Some patients experience significant benefit, while others may see more modest effects.

Naltrexone side effects: The most commonly reported side effects of oral naltrexone include:

• Nausea (the most frequent side effect, affecting roughly 10–15% of patients, often subsiding within the first week)
• Headache
• Dizziness
• Fatigue
• Insomnia
• Decreased appetite
• Anxiety

The injectable form (Vivitrol) can cause injection-site reactions, including pain, hardness, and occasionally induration or nodules. In rare cases, these reactions can be severe. Naltrexone carries a boxed warning for hepatotoxicity, though clinically significant liver injury at standard doses (50 mg/day) is rare. Liver function tests should be monitored, particularly in individuals with pre-existing liver disease.

A critical safety consideration: because naltrexone blocks opioid receptors, individuals who attempt to overcome the blockade by using large doses of opioids risk respiratory depression, coma, or death. Patients must be clearly counseled about this danger and should carry a medical alert card or bracelet indicating they are on naltrexone.

Acamprosate side effects: Acamprosate is generally well-tolerated. The most common side effect is diarrhea, which affects approximately 10–15% of patients and is usually mild. Other reported side effects include:

• Gastrointestinal discomfort (bloating, gas, nausea)
• Headache
• Insomnia
• Dizziness

Acamprosate has no known interactions with alcohol (it does not cause a disulfiram-like reaction) and minimal drug-drug interactions overall. However, it is contraindicated in severe renal impairment.

Limitations of both medications:

• Medication adherence is a significant challenge. Oral naltrexone requires daily compliance, and acamprosate requires taking six pills per day. Injectable naltrexone (Vivitrol) addresses the adherence issue but requires monthly office visits and is more costly.
• Neither medication eliminates cravings entirely or prevents relapse on its own. They reduce — but do not remove — the drive to drink.
• Individual variability in response is substantial. There are no widely available biomarkers or genetic tests to predict who will respond best to which medication, though research into pharmacogenomics is advancing.
• Stigma and underutilization: Despite strong evidence, these medications are dramatically underutilized. Research suggests that fewer than 10% of individuals with AUD receive any FDA-approved medication. Stigma around medication-assisted treatment — both among patients and within the healthcare system — remains a significant barrier.

Naltrexone and acamprosate can be prescribed by any physician, nurse practitioner, or physician assistant with prescribing authority — no special certification or waiver is required (unlike buprenorphine for opioid use disorder, which historically required a DEA waiver, though this requirement was eliminated in 2023). This means a primary care provider, psychiatrist, or addiction medicine specialist can prescribe these medications.

To find a provider experienced in treating alcohol use disorder with medication:

• SAMHSA's National Helpline: Call 1-800-662-4357 for free, confidential referrals to treatment facilities, support groups, and community-based organizations. This service is available 24/7, 365 days a year.
• SAMHSA Treatment Locator: Use the online tool at findtreatment.gov to search for providers and facilities offering medication-assisted treatment for AUD in your area.
• American Society of Addiction Medicine (ASAM): The ASAM provider directory lists board-certified addiction medicine physicians.
• Primary care providers: Many PCPs are increasingly trained and willing to prescribe medications for AUD. If your current provider is unfamiliar with these medications, ask for a referral to someone who is.
• Telehealth services: A growing number of telehealth platforms now offer evaluation and prescribing for AUD medications, which can improve access for individuals in rural areas or those facing transportation barriers.

When seeking a provider, look for someone who takes a comprehensive approach — combining medication with psychosocial support, monitoring progress over time, and adapting the treatment plan based on individual response.

Cost can be a meaningful barrier to treatment, though options exist to improve affordability:

Oral naltrexone: Generic oral naltrexone is relatively affordable. Without insurance, a month's supply typically costs between $30 and $90 at most pharmacies. With insurance or prescription discount programs (such as GoodRx), costs can be significantly lower. Most insurance plans, including Medicaid and Medicare, cover generic naltrexone.

Injectable naltrexone (Vivitrol): This is substantially more expensive. The wholesale acquisition cost exceeds $1,500 per monthly injection. However, many insurance plans cover it, particularly when prior authorization is obtained. The manufacturer (Alkermes) offers a patient assistance program for uninsured or underinsured individuals that can reduce or eliminate out-of-pocket costs.

Acamprosate: Generic acamprosate is available and is moderately priced, typically costing between $50 and $200 per month without insurance. Insurance coverage varies, and some plans may require prior authorization or step therapy (trying naltrexone first).

Insurance parity: Under the Mental Health Parity and Addiction Equity Act, most group health insurance plans and Medicaid programs are required to cover substance use disorder treatments — including medications — at levels comparable to coverage for general medical conditions. If a claim is denied, patients have the right to appeal.

Community health centers and public programs: Federally qualified health centers (FQHCs) offer services on a sliding fee scale based on income. Many state-funded substance use treatment programs also provide these medications at low or no cost. The 340B Drug Pricing Program enables qualifying healthcare organizations to purchase medications at significantly reduced costs, savings that are often passed on to patients.

Naltrexone and acamprosate are not the only evidence-based approaches to treating alcohol use disorder. Other options — which may be used as alternatives or in combination — include:

Other medications:

• Disulfiram (Antabuse): The third FDA-approved medication for AUD, disulfiram works by inhibiting the enzyme aldehyde dehydrogenase, causing an unpleasant reaction (flushing, nausea, vomiting, headache) if alcohol is consumed. It is most effective in highly motivated individuals with supervised administration.
• Topiramate: Although not FDA-approved specifically for AUD, topiramate has substantial evidence supporting its use in reducing heavy drinking. It works through modulation of GABA and glutamate systems. It is used off-label by many addiction specialists.
• Gabapentin: Also used off-label, gabapentin has emerging evidence for reducing heavy drinking and improving sleep and mood in individuals with AUD, particularly those with co-occurring anxiety or insomnia.

Psychosocial treatments:

• Cognitive-behavioral therapy (CBT): Helps individuals identify and modify thought patterns and behaviors that drive drinking.
• Motivational interviewing (MI) and motivational enhancement therapy (MET): Focus on building intrinsic motivation for change.
• Contingency management: Uses positive reinforcement (e.g., incentives) to reward abstinence.
• 12-step facilitation and mutual support groups: Alcoholics Anonymous and similar organizations provide peer support and a structured framework for recovery. SMART Recovery offers a secular, science-based alternative.
• Family and couples therapy: Addresses relational dynamics that contribute to or are affected by AUD.

Integrated treatment for co-occurring disorders: Because alcohol use disorder frequently co-occurs with depression, anxiety, PTSD, bipolar disorder, and other mental health conditions, integrated treatment that addresses both the substance use and the psychiatric condition simultaneously tends to produce the best outcomes.

If you recognize patterns in your drinking that concern you — such as difficulty cutting back despite wanting to, drinking more than intended, spending significant time obtaining or recovering from alcohol, experiencing cravings, or continuing to drink despite negative effects on your health, relationships, or responsibilities — these patterns may be consistent with alcohol use disorder, and professional evaluation is warranted.

You do not need to hit "rock bottom" to benefit from treatment. Early intervention improves outcomes. Alcohol use disorder exists on a spectrum, and medication-assisted treatment can be beneficial even for individuals with moderate severity who have not experienced catastrophic consequences.

Seek immediate medical attention if:

• You experience symptoms of alcohol withdrawal — such as tremors, sweating, rapid heartbeat, hallucinations, or seizures — when you stop or significantly reduce drinking. Alcohol withdrawal can be medically dangerous and potentially fatal, and should always be managed under medical supervision.
• You are having thoughts of self-harm or suicide. Alcohol use disorder significantly increases suicide risk. Contact the 988 Suicide and Crisis Lifeline (call or text 988) for immediate support.

Speaking with a primary care provider, psychiatrist, or addiction specialist is a strong first step. You can also contact SAMHSA's National Helpline at 1-800-662-4357 for free, confidential guidance and referrals at any time.