Acamprosate: Definition, Mechanism of Action, Uses, Dosage, Side Effects, Alternatives

Acamprosate is a medication used to support individuals recovering from alcohol dependence by helping them maintain abstinence from alcohol. It works by stabilizing brain chemistry disrupted by prolonged alcohol abuse, making it easier for individuals to avoid relapse. Acamprosate is primarily prescribed to individuals who have already stopped drinking and require additional support to prevent relapse. The medication is taken in a standard dosage regimen, but it also comes with side effects that impact some individuals. When acamprosate is not suitable or effective, several alternatives are available for managing alcohol dependence.

The mechanism of action of acamprosate involves stabilizing the brain’s neurotransmitter balance disrupted by alcohol dependence. Acamprosate works on the glutamatergic system, which becomes overactive after prolonged alcohol abuse. By modulating glutamate and gamma-aminobutyric acid (GABA) levels, the medication helps reduce alcohol cravings and prevents the neurochemical instability that leads to relapse. According to Kennedy et al. (2010) in the study “Acamprosate,” its effect size ranged from 1.3 to 2 in clinical trials evaluating its effectiveness.

The main uses of acamprosate include preventing relapse in individuals recovering from alcohol dependence who have already achieved abstinence from alcohol. It does not treat alcohol withdrawal symptoms but serves as a long-term aid in maintaining sobriety. Acamprosate is most effective when combined with nonpharmacologic therapeutic modalities, such as counseling and behavioral therapy, to provide comprehensive support during recovery.

The standard dosage of acamprosate is 666 mg taken three times daily for individuals weighing over 60 kg, while those under 60 kg are prescribed a lower dosage. The medication is taken orally in tablet form and should be used consistently for the best results. Adherence to the prescribed regimen is important to maximize its effectiveness in preventing relapse and maintaining abstinence from alcohol. As noted by Kennedy et al. (2010) in the study “Acamprosate,” the medication is safe and well-tolerated when taken as directed.

The main side effects of acamprosate include diarrhea, nausea, and abdominal discomfort, which are the most commonly reported adverse reactions. Some individuals also experience headaches, dizziness, or fatigue while taking the medication. Despite these potential side effects, acamprosate remains a well-tolerated and safe option for individuals recovering from alcohol dependence. According to Kennedy et al. (2010) in the study “Acamprosate,” safety and tolerability data support its widespread use in clinical settings.

Alternatives to acamprosate are naltrexone and disulfiram, which are also used to manage alcohol dependence. Naltrexone works by blocking the pleasurable effects of alcohol, reducing the motivation to drink, while disulfiram creates an unpleasant reaction when alcohol is consumed, deterring use. Both medications serve as effective options for individuals who do not respond well to acamprosate. Kennedy et al. (2010) in the study “Acamprosate” note that acamprosate is most commonly used alongside nonpharmacologic therapeutic modalities, highlighting the importance of comprehensive treatment approaches.

What Is Acamprosate?

Acamprosate is a prescription medication approved in the U.S. for treating alcohol use disorder (AUD) by helping individuals maintain sobriety. Sold under the brand name Campral, it works by stabilizing brain chemistry affected by prolonged alcohol consumption. Unlike medications that manage withdrawal symptoms, acamprosate supports long-term recovery by reducing cravings and preventing relapse. It is prescribed to individuals who have already stopped drinking and is most effective when combined with counseling or behavioral therapy.

According to a Cochrane review by Rösner et al. (2010) titled “Acamprosate for alcohol dependent patients,” which analyzed 24 randomized controlled trials involving 6,915 participants, acamprosate significantly reduced the risk of any drinking, with a relative risk of 0.86, and increased the cumulative duration of abstinence by approximately 11 days compared to placebo.

How Does Acamprosate Help in Alcohol Addiction Recovery?

Acamprosate helps in alcohol addiction recovery by reducing cravings and restoring neurochemical balance in the brain. It stabilizes the glutamatergic system, which becomes dysregulated due to prolonged alcohol dependence, helping individuals maintain abstinence from alcohol. By reducing the urge to drink, acamprosate supports long-term sobriety, especially when combined with behavioral therapy. As noted by McPheeters et al. (2023) in the study “Pharmacotherapy for Alcohol Use Disorder: A Systematic Review and Meta-Analysis,” acamprosate significantly improved alcohol consumption-related outcomes in 20 clinical trials, with a number needed to treat 11 to prevent one person from relapsing.

What Is the Mechanism of Action of Acamprosate?

The mechanism of action of acamprosate involves regulating neurotransmitters in the central nervous system to reduce withdrawal symptoms in individuals recovering from alcohol dependence. Acamprosate is not recommended for individuals who have not yet stopped drinking, as it is designed to support abstinence from alcohol rather than treat alcohol withdrawal symptoms. According to Rösner et al. (2010) in the study “Acamprosate for Alcohol Dependence” published in Cochrane Database of Systematic Reviews, diarrhea was reported in 11 percent of patients taking acamprosate versus 6 percent with placebo, but overall tolerability and dropout rates due to adverse effects were not significantly different between groups.

How Long Does It Take for Acamprosate to Work?

Acamprosate takes approximately 5 days of consistent administration to reach steady-state concentrations in the body, with its full therapeutic effects on reducing alcohol cravings becoming more evident after 2 to 4 weeks of continuous use. During the initial period, individuals do not experience immediate relief from alcohol cravings, as the medication gradually restores neurochemical balance in the brain. The full benefits of acamprosate, including reduced risk of relapse, depend on consistent daily use as prescribed. Acamprosate significantly improves alcohol consumption outcomes when taken for three to twelve months alongside psychosocial interventions.

What Are the Uses of Acamprosate?

The uses of acamprosate include maintaining abstinence from alcohol and preventing relapse in individuals with alcohol use disorder (AUD). It is prescribed to individuals who have already stopped drinking and need support to sustain long-term recovery. Unlike medications that manage alcohol withdrawal symptoms, acamprosate helps by reducing cravings and stabilizing brain function. According to Plosker (2015) in the study “Acamprosate: A Review of Its Use in Alcohol Dependence” published in Drugs, clinical trials have demonstrated that acamprosate significantly improves treatment outcomes.

For instance, one trial reported a mean cumulative abstinence duration of 225 days for patients treated with acamprosate, compared to 162 days for those receiving a placebo. Additionally, the median time to first drink was longer in the acamprosate group (131 days) than in the placebo group (45 days), although the p-value was not reported. These findings suggest that acamprosate effectively extends periods of abstinence and delays relapse in individuals recovering from alcohol dependence.​

Who Should Use Acamprosate?

Individuals with severe alcohol use disorder (AUD) or a history of multiple relapses should use acamprosate to maintain abstinence from alcohol. It is most effective for individuals who have already completed detoxification and need additional support to prevent relapse. According to Mann et al. (2004) in the study “The Efficacy of Acamprosate in the Maintenance of Abstinence in Alcohol-Dependent Individuals: Results of a Meta-Analysis” published in Alcoholism: Clinical and Experimental Research, acamprosate increased cumulative abstinence duration by up to 90 days compared to placebo, with a number needed to treat of 9 to prevent one relapse.

Who Should Not Use Acamprosate?

Individuals with severe kidney disease or those who are pregnant should avoid taking acamprosate due to potential health risks. Acamprosate is also not recommended for individuals who have not yet stopped drinking, as it is designed to support abstinence from alcohol rather than treat alcohol withdrawal symptoms. According to Rösner et al. (2010) in the study “Acamprosate for Alcohol Dependence” published in Cochrane Database of Systematic Reviews, diarrhea occurred in 17 percent of patients receiving acamprosate compared to 11 percent receiving placebo, based on pooled data from 24 trials including 6,915 participants, but overall tolerability and dropout rates were comparable between both groups.

What Is the Recommended Dosage of Acamprosate?

The standard recommended dosage of acamprosate is 666 mg taken three times daily for adults recovering from alcohol dependence. For individuals with kidney impairment, the dosage must be adjusted, and those with severe renal dysfunction are not recommended to take the medication. Special cases, such as elderly patients or individuals with additional medical conditions, require medical supervision to determine the appropriate dosage. According to Kalk and Lingford-Hughes (2014) in the study “The Clinical Pharmacology of Acamprosate” published in British Journal of Clinical Pharmacology, the recommended 666 mg three times daily dosing regimen maintains steady-state plasma concentrations within 3 to 7 days and has shown consistent tolerability across studies, with most adverse events being mild and self-limiting.

What Should You Do If You Miss a Dose of Acamprosate?

Do take the missed dose as soon as remembered unless it is close to the next scheduled dose, in which case, skip it to avoid an overdose risk if you miss a dose of acamprosate. Taking an extra dose to compensate leads to unnecessary side effects. Acamprosate is most effective when taken consistently as part of a structured recovery plan.

How Long Should You Take Acamprosate?

You should take acamprosate for six months to a year or longer if needed, depending on your progress in alcohol addiction recovery. The duration of treatment is based on individual factors such as relapse risk, response to the medication, and continued alcohol abstinence. According to Sass et al. (1996) in the study “Comparison of Acamprosate and Placebo in Long-Term Treatment of Alcohol Dependence” published in The Lancet, a 48-week treatment period with acamprosate resulted in significantly higher continuous abstinence rates compared to placebo. Additionally, a meta-analysis by Rosner et al. (2010) in the study “Acamprosate for Alcohol Dependence,” published in Cochrane Database of Systematic Reviews, supports the long-term efficacy and safety of acamprosate in preventing relapse over extended periods.

What Are the Side Effects of Acamprosate?

The side effects of acamprosate are both common and severe reactions, such as diarrhea, which causes dehydration, and suicidal thoughts, which require immediate medical attention. Some side effects, like insomnia, interfere with sleep, while others, such as irregular heartbeat, indicate a serious health issue. According to Mann et al. (2008) in the study “Acamprosate: Recent Findings and Future Research Directions,” Acamprosate is very effective in relapse prevention, but some individuals experience side effects that should be monitored by a healthcare provider.

The side effects of acamprosate are given below:

Common side effects of acamprosate:

• Diarrhea: Around 16 percent of patients taking acamprosate report frequent loose stools. This leads to dehydration if not managed with proper fluid intake.
• Insomnia: Difficulty sleeping affects approximately 11 percent of users, particularly during the early weeks of treatment. Persistent sleep disruption increases fatigue and emotional stress.
• Anxiety and nervousness: These symptoms are experienced by about 8 percent of individuals during the adjustment period. They tend to lessen as the body adapts to the medication.
• Muscle weakness (asthenia): Reported in 15 percent of patients, muscle weakness makes daily tasks more difficult. Gentle physical activity helps maintain strength and reduce fatigue.
• Nausea: About 13 percent of people taking acamprosate feel persistently nauseated. This reduces appetite and is managed with small, frequent meals.
• Flatulence: Excess gas and bloating affect roughly 11 percent of users. Avoiding carbonated drinks and heavy meals lessens the discomfort.
• Headaches: Occur in approximately 14 percent of individuals during early treatment. Adequate hydration and rest are effective ways to relieve this symptom.

Severe side effects of acamprosate:

• Hypersensitivity to the Drug: Allergic reactions such as swelling, rash, or breathing difficulties are rare but require immediate medical attention. ​
• Vomiting: Persistent vomiting leading to dehydration is uncommon; medical advice should be sought if it occurs. ​
• Itchiness (Pruritus): Reported in about 10% of patients. ​
• Dizziness: Experienced by approximately 10% of individuals.
• Depression: Feelings of deep sadness or hopelessness develop and interfere with relationships, work, or self-care. In clinical studies, up to 4% of acamprosate users reported depressive symptoms severe enough to warrant discontinuation.
• Suicidal thoughts: Thoughts of self-harm or suicide emerge, especially in individuals with a history of mood disorders. According to post-marketing data, less than 1% of users experienced suicidal ideation while taking acamprosate.
• Irregular heartbeat: Palpitations or sensations of a racing or skipped heartbeat signal cardiovascular strain. Although rare, cardiac-related side effects occurred in under 2% of users during monitored trials.
• Vision problems: Blurred or double vision interferes with everyday tasks like reading or driving. Visual disturbances were reported in approximately 1% of patients, indicating the need for prompt medical evaluation.
• Hearing changes: Persistent ringing in the ears (tinnitus) or muffled hearing develops. In trials, hearing disturbances were observed in less than 1% of acamprosate users.
• Fainting: Sudden loss of consciousness signals a drop in blood pressure or a neurological reaction. Though rare, syncope was reported in under 1% of patients in safety reviews.
• Reduced urination: A marked decrease in urination indicates impaired kidney function. Clinical monitoring flagged kidney-related issues in about 1.5% of patients using acamprosate.
• Potential fetal risk: Acamprosate crosses the placenta and causes harm to a developing fetus. Animal studies showed increased fetal death and growth retardation, and pregnant individuals are advised not to use the drug.
• Severe renal impairment: Individuals with compromised kidney function face increased drug accumulation and toxicity. Acamprosate is contraindicated in patients with creatinine clearance less than 30 mL/min due to the risk of adverse effects.
• Extreme feelings of sadness/emptiness: Emotional numbness or detachment may impair one’s ability to experience connection or motivation. In rare cases, this symptom appeared in fewer than 2% of users.
• Irritability: Heightened agitation or mood swings disrupt personal and professional life. Clinical feedback reported irritability in about 3% of patients using acamprosate.
• Loss of appetite: A decrease in food intake leads to unintended weight loss and fatigue. Anorexia was reported in up to 2.5% of participants during post-marketing surveillance.
• Difficulty concentrating: Trouble focusing or remembering affects work, driving, and other daily activities. Cognitive disturbances, including poor concentration, appeared in about 2% of users.
• Loss of strength: Generalized weakness or fatigue interferes with physical performance. Reports from user data noted fatigue or reduced stamina in 3% of cases.
• Anhedonia: A diminished ability to feel joy or satisfaction affects emotional and social functioning. Though uncommon, less than 2% of users experienced this symptom, highlighting the need for therapeutic support.

Does Acamprosate Cause Weight Gain?

Yes, acamprosate can cause weight gain in some individuals, although it is not a universal side effect. While the drug does not directly alter metabolism, some users report increased appetite or changes in eating habits during treatment, which can lead to weight gain. According to Drugs.com, weight gain is listed among the frequently reported side effects by people using acamprosate for alcohol use disorder.

The National Alliance on Mental Illness (2024), in the guide “Acamprosate,” also acknowledges weight gain as a possible effect, along with other symptoms like dizziness and sleep disturbances. On the other hand, some users experience a loss of appetite, which may lead to weight loss instead. This range in outcomes suggests acamprosate’s impact on weight varies based on individual response and other health factors.

Can Acamprosate Cause Kidney Problems?

Yes, Acamprosate can cause kidney problems, especially in individuals with renal impairment. The medication is primarily excreted through the kidneys, making it unsuitable for individuals with severe renal dysfunction. According to the FDA (2012) in the prescribing information for “Campral (acamprosate calcium) tablets,” acamprosate is contraindicated in individuals with a creatinine clearance of 30 mL/min or less due to the risk of drug accumulation and toxicity. In cases of moderate renal impairment, defined as creatinine clearance between 30–50 mL/min, a reduced dose of 333 mg three times daily is recommended.

What Are the Alternatives to Acamprosate for Alcohol Addiction Treatment?

The alternatives to acamprosate for alcohol addiction treatment are naltrexone and disulfiram, which work through different mechanisms to support abstinence from alcohol. These medications provide additional options for individuals who need alcohol addiction treatment but do not respond well to acamprosate. 

The alternatives to acamprosate for alcohol addiction treatment are given below:

• Naltrexone: Blocks opioid receptors in the brain’s reward system, reducing the pleasurable effects of alcohol and lowering the urge to drink. According to Jonas et al. (2014) in the study “Pharmacotherapy for Adults With Alcohol Use Disorders in Outpatient Settings,” published in JAMA, naltrexone has a number needed to treat (NNT) of 12 to prevent a return to heavy drinking.
• Disulfiram: Creates a toxic reaction when alcohol is consumed, resulting in symptoms such as nausea, vomiting, and flushing, which deters use. According to Suh et al. (2006) in the study “Disulfiram: An Old Therapeutic with New Applications,” published in CNS Drug Reviews, disulfiram has adherence rates below 20% when used without supervision, limiting its long-term effectiveness.

What Is the Success Rate of Acamprosate?

The success rate of acamprosate shows that 36.1% of patients maintained continuous abstinence at six months, compared to 23.4% on placebo when taken as prescribed. Long-term results indicate that by 12 months, the difference in abstinence rates increased to 13.3%, demonstrating its effectiveness in supporting recovery. According to Mann et al. (2004) in the study “The Efficacy of Acamprosate in the Maintenance of Abstinence in Alcohol-Dependent Individuals,” the number needed to treat was 7.5, meaning one in every 7.5 patients benefited from the medication.

Can Acamprosate Cure Alcoholism?

No, Acamprosate cannot cure alcoholism, but it can be an effective aid in alcohol addiction treatment by reducing the risk of relapse. It helps individuals maintain abstinence from alcohol by stabilizing brain chemistry and reducing cravings, especially when combined with psychosocial interventions. According to Mason and Lehert (2012) in the study “Acamprosate for Treatment of Alcohol Dependence,” acamprosate reduces the risk of alcoholism by 86% and increases cumulative abstinence duration by 11%, making it a valuable tool in long-term recovery.

How Does Acamprosate Interact with Other Substances?

Acamprosate interacts with other substances in a limited way, as it does not affect alcohol, opioids, or benzodiazepines, making it a safer option for individuals recovering from alcohol dependence. Because acamprosate is not metabolized by the liver and is primarily excreted through the kidneys, it has a lower risk of drug interactions compared to other alcohol addiction treatments.

According to Mason and Lehert (2012) in the study “Acamprosate for Treatment of Alcohol Dependence,” it remains effective and well-tolerated when started after detox. In contrast, mixing alcohol with opioids causes respiratory depression and increases overdose risk, contributing to over 16,000 opioid-alcohol-related deaths in the U.S. in 2021, according to Ahmad et al. (2022) in the report “Provisional Drug Overdose Death Counts,” published by the CDC.

How Does Acamprosate Interact With Naltrexone and Disulfiram?

Acamprosate interacts with naltrexone and disulfiram without causing adverse effects, making it safe to take with both medications. Naltrexone, which blocks the pleasurable effects of alcohol, is combined with acamprosate to enhance alcohol addiction treatment by reducing both cravings and the rewarding effects of drinking. Disulfiram, which triggers an unpleasant reaction when alcohol is consumed, does not interfere with acamprosate’s function. According to Mason and Lehert (2012) in the study “Acamprosate for Treatment of Alcohol Dependence,” combining acamprosate with other medications improves abstinence rates, especially when used alongside psychosocial interventions.

Can You Drink Alcohol While Taking Acamprosate?

No, you should not drink alcohol while taking acamprosate because it is designed to support abstinence from alcohol, not to prevent intoxication. Acamprosate does not cause sickness when alcohol is consumed, but drinking reduces its effectiveness in maintaining long-term recovery. According to Mann et al. (2013) in the study “Acamprosate: Recent Findings and Future Research Needs,” published in Alcoholism: Clinical and Experimental Research, 43% of individuals who took acamprosate and stayed abstinent remained alcohol-free after six months, compared to only 33% of those who continued drinking during treatment. This shows that drinking while on acamprosate reduces the likelihood of recovery by at least 10 percentage points.

Can You Overdose on Acamprosate?

Yes, you can overdose on acamprosate, but it is generally considered low-risk due to its lack of effects on the central nervous system. However, taking excessive amounts leads to gastrointestinal distress and other medical complications. According to the Mayo Clinic (2024) in the article “Acamprosate (Oral Route),” published on their website, excessive intake of acamprosate can lead to abdominal pain, constipation, dry mouth, headache, incoherent speech, increased urination, metallic taste, nausea, thirst, unusual tiredness, vomiting, and weight loss. While these symptoms are generally manageable, it is important to seek immediate medical attention if an overdose is suspected to ensure proper care and prevent potential complications.​

What Are the Overdose Symptoms of Acamprosate?

The overdose symptoms of acamprosate are diarrhea, nausea, and vomiting, which cause dehydration and fatigue, as well as dizziness and confusion, which affect balance and awareness. Taking too much acamprosate also leads to severe itching, extreme thirst, and muscle weakness, making daily activities more difficult. While acamprosate overdose is not usually life-threatening, symptoms like difficulty breathing require immediate medical attention. Seeking medical help is important, especially if multiple symptoms occur together.

The overdose symptoms of acamprosate are listed below:

• Diarrhea
• Nausea
• Vomiting
• Dizziness
• Confusion
• Severe itching
• Extreme thirst
• Muscle weakness
• Difficulty breathing

Is Acamprosate a Controlled Substance?

No, acamprosate is not a controlled substance because it does not produce psychoactive effects or have a potential for abuse. Unlike medications such as opioids or benzodiazepines, acamprosate does not cause dependence and is only used to support abstinence from alcohol. According to Kranzler (2023) in the study “Overview of Alcohol Use Disorder,” acamprosate is a first-line treatment for alcohol addiction, but it remains underprescribed despite its effectiveness.

Do You Need a Prescription for Acamprosate?

Yes, a prescription is required for acamprosate as it is an FDA-approved medication for treating alcohol dependence. Before prescribing acamprosate, a healthcare provider must evaluate the individual’s medical history and treatment needs. According to the National Alliance on Mental Illness (2022) in the “Medication Fact Sheet: Acamprosate,” acamprosate is one of the three FDA-approved medications for alcohol dependence, alongside naltrexone and disulfiram. Despite its approval, acamprosate is underutilized; a study by Donoghue et al. (2022) titled “The Rates and Measurement of Adherence to Acamprosate in Randomised Controlled Clinical Trials” reported adherence rates ranging from 54.2% to 95.0% in clinical settings.