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

Acamprosate is a medication used to help individuals maintain abstinence from alcohol after they have stopped drinking. In a study “Safety and Efficacy of Acamprosate for the Treatment of Alcohol Dependence” by Stephanie L Yahn, et al. 2013, Acamprosate has been utilized in the treatment of alcohol addiction with pharmacovigilance data indicating that over 1.5 million patients have been treated without serious health risks.

The exact mechanism by which acamprosate functions remains not fully understood. It is believed to interact with neurotransmitter systems, potentially stabilizing chemical signaling in the brain that is disrupted by alcohol withdrawal.

Acamprosate is primarily used to assist individuals who have ceased drinking in maintaining abstinence from alcohol. It is used in conjunction with counseling and social support. The medication does not prevent withdrawal symptoms experienced during initial cessation but aids in sustaining sobriety thereafter. Its efficacy is most pronounced when integrated into a comprehensive treatment program that includes psychosocial support. A meta-analysis “Acamprosate (Campral) for Treatment of Alcoholism” by KAM HUNTER, et al., revealed that at six months, 36% of patients treated with acamprosate remained continuously abstinent, compared to 23% in the placebo group.

The standard dosage for acamprosate is two 333 mg tablets taken three times daily, totaling 1998 mg daily. This regimen is continued for one year.

Common side effects associated with acamprosate include diarrhea, nausea, depression, and anxiety. Diarrhea is the most frequently reported adverse effect, occurring in up to 17% of patients, reported by Drugs.com. In clinical trials, these adverse effects have led some individuals to discontinue use of the medication.

Alternatives to acamprosate for treating alcohol addiction include naltrexone and disulfiram. Naltrexone works by blocking the rewarding effects of alcohol, thereby reducing cravings. Disulfiram deters alcohol consumption by inducing unpleasant reactions when alcohol is ingested. 

What Is Acamprosate?

Acamprosate is a prescription medication approved by the U.S. Food and Drug Administration (FDA) in 2004 for treating alcohol use disorder (AUD). It is known for its brand name, Campral. 

Its primary function is to help individuals who have stopped drinking alcohol maintain abstinence. The exact mechanism by which acamprosate functions is not fully understood, but it is believed to interact with neurotransmitter systems, potentially stabilizing chemical signaling in the brain disrupted by alcohol withdrawal. 

Research has demonstrated its efficacy; for instance, a meta-analysis “The clinical pharmacology of acamprosate” by Nicola J Kalk, et al. 2014, indicated that patients treated with acamprosate had a 14% lower risk of returning to any drinking compared to those on placebo, with a number needed to treat (NNT) of 9 to prevent one additional patient from relapsing. Since its approval, acamprosate has been widely utilized in the management of AUD, contributing to improved abstinence rates among individuals seeking to overcome alcohol dependence.

What Is the Mechanism of Action of Acamprosate?

The mechanism of action of acamprosate involves modulating neurotransmitter systems in the central nervous system, particularly affecting glutamate and gamma-aminobutyric acid (GABA) pathways. Chronic alcohol consumption disrupts the balance between excitatory and inhibitory neurotransmission, leading to neurochemical imbalances. Acamprosate is believed to restore this balance by normalizing N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic neurotransmission and modulating GABA_A receptor activity. This dual action helps alleviate the hyperexcitability associated with alcohol withdrawal, thereby reducing withdrawal symptoms and supporting abstinence in individuals with alcohol dependence. ​

Patients treated with acamprosate maintained cumulative abstinence for 11% longer than those taking a placebo, as reported by a study “Effectiveness of Acamprosate in the Treatment of Alcohol Dependence” by William E. Cayley, 2011. Acamprosate’s role in enhancing abstinence rates and reducing relapse in individuals recovering from alcohol dependence. The modulation of acamprosate helps alleviate the hyperexcitability associated with alcohol withdrawal, thereby supporting abstinence in individuals with alcohol dependence.

How Long Does It Take for an Acamprosate to Work?

Acamprosate takes five days of consistent use to work. To achieve optimal benefits, it is essential to continue taking the medication as prescribed, even if immediate changes are not apparent. Continuous use of acamprosate has been associated with improved outcomes, for instance, a meta-analysis “Efficacy of acamprosate for the treatment of alcohol dependence long after recovery from withdrawal syndrome” by Susumu Higuchi, et al. 2015, indicated that patients treated with acamprosate had a 14% lower risk of returning to any drinking compared to those on placebo. Therefore, maintaining adherence to the prescribed regimen is necessary for enhancing the likelihood of sustained abstinence from alcohol.

What Are the Uses of Acamprosate?

The uses of acamprosate include supporting individuals with alcohol use disorder (AUD) in maintaining abstinence from alcohol. Its primary function is to help individuals who have stopped drinking large amounts of alcohol maintain abstinence from alcohol. Clinical studies have demonstrated its efficacy in relapse prevention; for instance, a study “Relapse prevention by acamprosate” by H Sass, et al., revealed that patients receiving acamprosate had a significantly higher continuous abstinence rate within the first 60 days of treatment compared to those on placebo (67% vs. 50%).

Another analysis “The clinical pharmacology of acamprosate” by Nicola J Kalk, et al. 2014, found that patients taking acamprosate had a 14% lower risk of returning to any drinking compared to those on placebo, with a number needed to treat (NNT) of 9 to prevent one additional patient from relapsing. These findings underscore acamprosate’s effectiveness in supporting sustained abstinence and reducing the likelihood of relapse in individuals recovering from AUD.​

Are There Any Off-Label Uses of Acamprosate?

Yes, there are off-label uses of acamprosate. It has been explored beyond its primary indication for alcohol use disorder. Notably, an open-label study “Open-Label Trial of Acamprosate as a Treatment for Anxiety” by Marc Hertzman, et al. 2009, investigated its potential in treating anxiety disorders, demonstrating a significant reduction in anxiety symptoms among participants. However, these findings are preliminary, and further research is necessary to establish its efficacy and safety for such off-label applications.

Who Should Use Acamprosate?

Acamprosate should be used by individuals with alcohol use disorder (AUD) who have achieved abstinence and seek to maintain it. It is particularly beneficial for those with severe AUD or a history of multiple relapses. Clinical studies, for instance, “Effectiveness of Acamprosate in the Treatment of Alcohol Dependence” by William E. Cayley, 2011. have demonstrated that acamprosate reduces the risk of returning to any drinking and improves cumulative abstinence rates when used in conjunction with detoxification and psychosocial interventions. However, acamprosate is contraindicated in patients with severe renal impairment.

Who Should Not Use Acamprosate?

Individuals with severe renal impairment should avoid taking acamprosate, as it is contraindicated in such cases. Patients with moderate renal impairment should have their dosage reduced to one 333 mg tablet taken three times daily. Additionally, caution is advised for pregnant or breastfeeding women and those with a known hypersensitivity to acamprosate or its components.

What Is the Recommended Dosage of Acamprosate?

The standard recommended dose of acamprosate is 666 mg, administered as two 333 mg tablets taken three times daily. For patients with moderate renal impairment (creatinine clearance between 30–50 mL/min), the dosage is reduced to one 333 mg tablet taken three times daily. Acamprosate is contraindicated in individuals with severe renal impairment (creatinine clearance ≤30 mL/min). Treatment commences as soon as possible after the withdrawal period, once the patient has achieved abstinence, and maintained it even if the patient relapses.  Acamprosate is used as part of a comprehensive psychosocial treatment program. 

Adherence to the prescribed acamprosate regimen is necessary for its effectiveness. A study “Adherence to Prescribed Acamprosate in Alcohol Dependence and 1-Year Morbidities and Mortality” by Serenella Tolomeo, et al. 2021, found that at six months after starting acamprosate, only 6% of individuals had followed the recommended minimum 6-month treatment. Moreover, individuals with low adherence were at a significantly higher risk of death and morbidities within 12 months of starting acamprosate. Therefore, patients need to adhere to the prescribed dosage and duration of acamprosate therapy to achieve optimal outcomes in the treatment of alcohol dependence.

How Long Should You Take Acamprosate?

You should take Acamprosate for a duration ranging from six months to a year to assist you in maintaining abstinence from alcohol. The specific length of treatment depends on individual factors, including the severity of alcohol dependence and the patient’s progress in recovery. Research has demonstrated that acamprosate is both safe and effective for long-term use. For instance, a study “Comparison of acamprosate and placebo in long-term treatment of alcohol dependence” by A.B Whitworth, et al., assessing the efficacy and safety of long-term acamprosate treatment in alcohol dependence found that patients receiving acamprosate were more likely to remain abstinent over one year compared to those on placebo.

Additionally, a meta-analysis “Efficacy of acamprosate for the treatment of alcohol dependence long after recovery from withdrawal syndrome” by Susumu Higuchi, et al. 2015, indicated that patients treated with acamprosate had a 14% lower risk of returning to any drinking compared to those on placebo. Therefore, the duration of acamprosate therapy is tailored to each patient’s needs and continues as long as it contributes positively to their recovery journey.​

Can You Take Acamprosate with an Empty Stomach?

Yes, acamprosate can be taken on an empty stomach. A study by the United States Department of Veterans Affairs suggests that taking it on an empty stomach enhances its effectiveness. However, if it causes an upset stomach, it is taken with food. Taking it with meals also helps maintain a consistent routine, aiding in adherence to the prescribed dosing schedule.

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

Take it as soon as you remember, if you miss a dose of acamprosate. However, if it is almost time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take extra medicine to make up for the missed dose, as this increases the risk of side effects.

What Are the Side Effects of Acamprosate?

The side effects of acamprosate include accidental injury, bloated or full feeling

burning, crawling, itching, numbness gas, upset stomach, loss of appetite, and serious reactions. Common side effects are diarrhea, gas, upset stomach, loss of appetite, dry mouth, dizziness, itching, weakness, nausea, anxiety, difficulty sleeping, and sweating. Serious side effects, though less common, include burning, tingling, or numbness in the extremities, and rash. It’s important to monitor for symptoms of depression, such as feelings of sadness, hopelessness, or thoughts of self-harm, as acamprosate increases the risk of suicidal thoughts or behavior. Patients experiencing any severe or persistent side effects contact their healthcare provider promptly.

Common Side Effects of Acamprosate

The common side effects of Acamprosate include discouragement, feeling sad, irritability, lack of appetite, lack or loss of strength, loss of interest or pleasure, nervousness, sleeplessness, tiredness, trouble concentrating, and trouble sleeping. These side effects are generally mild and diminish as your body adjusts to the medication.

Common side effects of acamprosate include:

• Discouragement and Feeling Sad: These terms refer to feelings of despondency or unhappiness. According to a study published by Drugs.com, 1% to 10% of patients on acamprosate report depression. Management includes monitoring mood changes and consulting healthcare providers if symptoms persist.
• Irritability: This involves feelings of agitation or frustration. Related symptoms like anxiety occur. Patients are advised to discuss persistent irritability with their doctors.​ A study “Glutamatergic dysfunction in schizophrenia” by Rodrigo D. Paz, et al. 2008, mentioned that acamprosate seems to induce a relatively higher risk of suicidal thoughts and attempted suicide (2.4%) when compared to placebo (0.8%). However, the incidence of completed suicide in patients receiving acamprosate (0.13%) resembled that observed in the placebo group (0.10%)
• Lack of Appetite: A reduced desire to eat. Loss of appetite is among the common side effects. Maintaining a balanced diet and consulting a healthcare provider help address this issue.​ According to a study “ The effect of acamprosate on alcohol and food craving in patients with alcohol dependence” by Doug Hyun Han, et al. 2008, the influence of acamprosate for reducing craving for alcohol and food was assessed in 204 in-patients with alcohol dependence and there was a significant reduction in craving for alcohol over 4 weeks of treatment.
• Lack or Loss of Strength: This pertains to feelings of weakness or decreased physical power. This side effect is managed by adjusting activity levels and seeking medical advice if it continues. ​
• Loss of Interest or Pleasure: Known as anhedonia, this is a reduced ability to enjoy activities. It’s important to monitor these feelings and consult a healthcare professional for guidance.​
• Nervousness: Feelings of unease or worry. Some patients experience nervousness during treatment.
• Sleeplessness and Trouble Sleeping: These refer to difficulties in falling or staying asleep. Establishing a regular sleep routine and consulting a healthcare provider is beneficial.​ In a study “Insomnia in Alcohol-Dependent Patients” by Pascal Perney, et al. 2018, Acamprosate has been shown to decrease insomnia in abstinent patients. Twelve studies were found including 3508 patients. After a 6-month follow-up, the mean insomnia decrease over baseline was -26% and -45% for the placebo and acamprosate groups, respectively.
• Tiredness: A state of fatigue or weariness. Managing tiredness involves adequate rest and discussing persistent symptoms with a doctor.
• Trouble Concentrating: Difficulty focusing on tasks. Patients experiencing this consult their healthcare provider for appropriate strategies.​

Serious Side Effects of Acamprosate

The serious side effects of Acamprosate include accidental injury, bloated or full feeling

burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings, dizziness, dry mouth, excess air or gas in stomach or intestines, itching skin, pain, passing gas, and sweating. If any of these serious side effects are experienced, it is necessary to seek medical attention. 

Serious side effects of acamprosate include

• Accidental Injury: This refers to unintended harm or damage to the body, such as cuts, bruises, or fractures, occurring without deliberate cause. Some individuals experience dizziness or coordination issues, potentially increasing the risk of such injuries. ​
• Bloated or Full Feeling: This sensation involves abdominal swelling or a feeling of fullness, often due to gas accumulation or slowed digestion. Patients on acamprosate have reported such gastrointestinal discomforts. ​
• Paresthesia: Described as burning, crawling, itching, numbness, prickling, “pins and needles,” or tingling sensations, paresthesia results from nerve irritation or damage. Some acamprosate users have reported these sensory disturbances.
• Dizziness: This is a feeling of lightheadedness, unsteadiness, or a sensation that the surroundings are spinning. Dizziness is among the side effects noted by individuals taking acamprosate. Occurs in 3% of patients, reported by the U.S. Food and Drug Administration (FDA).
• Dry Mouth: A condition where the mouth feels unusually dry, due to reduced saliva production. Acamprosate users have occasionally reported experiencing dry mouth. ​
• Excess Air or Gas in the Stomach or Intestines: This leads to sensations of bloating, discomfort, and the need to belch or pass gas. Such symptoms have been observed in some individuals on acamprosate.
• Itching Skin: An uncomfortable sensation prompting the desire to scratch. Some patients taking acamprosate have reported itching as a side effect. Reported in about 4% of patients by the U.S. Food and Drug Administration (FDA).
• Pain: This encompasses a range of discomforts, from mild aches to severe distress, in various body parts. While pain is a broad symptom, some acamprosate users have noted experiencing it. ​
• Passing Gas: Also known as flatulence, this is the release of excess gas from the digestive system through the rectum. It’s a common occurrence and has been reported by some on acamprosate. ​
• Sweating: The body’s natural process of releasing fluid through the skin’s sweat glands, in response to heat, physical activity, or stress. Increased sweating has been observed in certain individuals taking acamprosate. ​

Patients must monitor these side effects and consult their healthcare provider if they experience persistent or severe symptoms.

Does Acamprosate Cause Weight Gain?

Yes, acamprosate causes weight gain in some individuals. Clinical studies have reported weight gain as a side effect in patients taking acamprosate. According to a study “Does acamprosate cause weight gain?” published by Drugs.com, weight gain is frequently reported as a side effect of acamprosate by people taking this medication to control alcohol cravings associated with alcohol use disorder. Specifically, patients taking acamprosate along with antidepressants more commonly reported both weight gain and weight loss, compared with patients taking either medication alone.

Additionally, some individuals experience increased appetite after starting acamprosate, though it’s unclear if this is due to the medication or a response to ceasing alcohol consumption. Therefore, while weight gain is a possible side effect, it does not occur in all individuals.

Can Acamprosate Cause Kidney Problems?

Yes, acamprosate can cause kidney problems, particularly in individuals with pre-existing renal impairment. According to a study “Safety and Efficacy of Acamprosate for the Treatment of Alcohol Dependence” by Stephanie L Yahn, et al. 2013, the medication is primarily excreted unchanged by the kidneys, leading to elevated plasma concentrations in patients with reduced renal function. Consequently, acamprosate is contraindicated in patients with severe renal impairment and requires dosage reduction in those with moderate impairment. Additionally, there have been reports of acute renal failure associated with acamprosate use. Therefore, assessing kidney function before initiating treatment and monitoring renal parameters during therapy is essential to mitigate potential risks.​

What Are the Alternative Medications to Acamprosate for Alcohol Addiction?

The alternative medications to acamprosate for alcohol addiction are naltrexone and disulfiram. Each operates through distinct mechanisms and offers unique benefits. Both medications offer valuable tools in the management of alcohol use disorder, with naltrexone focusing on reducing cravings and disulfiram acting as a deterrent through aversive conditioning. 

Naltrexone: An opioid receptor antagonist, naltrexone works by blocking the euphoric and pleasurable effects of alcohol consumption. By interfering with the brain’s reward pathways associated with drinking, it reduces cravings and the desire to consume alcohol. Clinical studies, for instance, “Naltrexone and the Treatment of Alcohol Dependence” by Joseph R Volpicelli, et al., have demonstrated that naltrexone significantly decreases excessive alcohol drinking, making it an effective option for individuals aiming to reduce heavy drinking days and promote abstinence.

Disulfiram: This medication inhibits the enzyme acetaldehyde dehydrogenase, leading to an accumulation of acetaldehyde when alcohol is consumed. The resulting buildup causes unpleasant physiological reactions such as flushing, nausea, vomiting, and headaches. These adverse effects serve as a deterrent, discouraging individuals from consuming alcohol. Disulfiram is most effective in motivated individuals who are committed to maintaining abstinence, as the anticipation of these negative reactions reinforces avoidance of alcohol intake.

The choice between them is tailored to the individual’s treatment goals, medical history, and personal preferences, ideally in consultation with a healthcare professional.

How Does Acamprosate Differ from Other Alcohol Addiction Medications?

​Acamprosate differs from other alcohol addiction medications in its mechanism of action and effectiveness. While acamprosate modulates neurotransmitter systems to maintain abstinence, naltrexone blocks the rewarding effects of alcohol, and disulfiram induces adverse reactions upon alcohol consumption. 

Acamprosate: Patients treated with acamprosate maintained cumulative abstinence for 11% longer than those taking a placebo, reported by a meta-analysis “Effectiveness of Acamprosate in the Treatment of Alcohol Dependence” by WILLIAM E. CAYLEY, 2011,  indicated that acamprosate is effective in supporting continuous abstinence after detoxification in alcohol-dependent patients.

Naltrexone: In a one-year follow-up study “NALTREXONE VERSUS ACAMPROSATE: ONE YEAR FOLLOW-UP OF ALCOHOL DEPENDENCE TREATMENT” by G. Rubio, et al. 2001, 41% of patients receiving naltrexone had not relapsed, demonstrating its efficacy in reducing relapse rates.

Disulfiram: A recent meta-analysis “Perspectives on the pharmacological management of alcohol use disorder” by Mariangela Antonelli, et al. 2022, including 22 studies, showed a higher success rate of disulfiram compared to controls. However, only open-label trials showed a significant superiority over controls, while randomized controlled trials with double-blind design failed to show a significant efficacy of the drug.

These findings suggest that while all three medications are beneficial, their effectiveness varies, and the choice of treatment is tailored to individual patient needs and circumstances.

Can Acamprosate and Naltrexone Be Taken Together?

Yes, Acamprosate and Naltrexone can be taken together to enhance treatment outcomes for alcohol dependence. Acamprosate works by stabilizing neurotransmitter systems disrupted by chronic alcohol use, thereby reducing withdrawal symptoms and supporting abstinence. Naltrexone, on the other hand, is an opioid receptor antagonist that diminishes the rewarding effects of alcohol, leading to reduced cravings and consumption. It has been shown that combining these medications is more effective than monotherapy. For instance, a double-blind, placebo-controlled study “Comparing and Combining Naltrexone and Acamprosate in Relapse Prevention of Alcoholism” by Falk Kiefer, et al. 2003, found that the combination therapy significantly lowered relapse rates compared to placebo and acamprosate alone, although it was not significantly more effective than naltrexone alone.

Another study “Combined therapy: what does acamprosate and naltrexone combination tell us?” by Klaus Wiedemann, et al. 2004,  reported that combined treatment was superior to both placebo and acamprosate monotherapy, with sustained benefits observed after a 12-week follow-up period. These findings suggest that using acamprosate and naltrexone together provides a synergistic effect, improving the chances of maintaining abstinence in individuals with alcohol dependence.​

Can Acamprosate and Disulfiram Be Used Together?

Yes, Acamprosate and Disulfiram can be used together to enhance treatment outcomes for alcohol dependence. Disulfiram creates an aversion to alcohol by inhibiting the enzyme acetaldehyde dehydrogenase, leading to unpleasant reactions such as flushing, nausea, and palpitations when alcohol is consumed. This deters individuals from drinking. Acamprosate, on the other hand, helps maintain abstinence by stabilizing neurotransmitter systems disrupted by chronic alcohol use, reducing withdrawal symptoms and cravings.

A study “Combined efficacy of acamprosate and disulfiram in the treatment of alcoholism: by J Besson, et al., found that patients receiving both medications had better outcomes, with a mean cumulative abstinence duration (CAD) of 137 days, compared to 75 days for those on placebo. No adverse interactions between acamprosate and disulfiram were observed, suggesting that their combined use is safe and more effective than monotherapy.

Can Acamprosate Cure Alcohol Addiction?

No, acamprosate does not cure alcohol addiction. It serves as a supportive treatment to help maintain abstinence in individuals recovering from alcohol dependence. Its primary function is to stabilize neurotransmitter systems disrupted by alcohol addiction, thereby reducing withdrawal symptoms and cravings. A study “Effectiveness of Acamprosate in the Treatment of Alcohol Dependence” by WILLIAM E. CAYLEY, 2011, has demonstrated that acamprosate is effective in reducing the risk of relapse when used in conjunction with detoxification and psychosocial interventions. However, its effects are considered moderate, and it is most beneficial as part of a comprehensive treatment plan that includes counseling and support. Therefore, while acamprosate aids in the management of alcohol dependence, it is not a standalone cure.

How Effective Is Acamprosate in Treating Alcohol Dependence?

Acamprosate is 86% effective in treating alcohol dependence by supporting abstinence and reducing relapse rates. A meta-analysis of 24 trials revealed that patients taking acamprosate had a 14% lower risk of returning to any drinking compared to those on placebo, corresponding to a number needed to treat (NNT) of 9 to prevent one additional patient from relapsing.

Additionally, According to a study “Acamprosate for treatment of alcohol dependence: mechanisms, efficacy, and clinical utility” by Katie Witkiewitza, et al. 2012, acamprosate-treated patients experienced an 11% increase in cumulative abstinence duration. However, its effects are considered moderate, and it is most beneficial as part of treating alcohol dependence that includes counseling and support. Therefore, while acamprosate aids in the management of alcohol dependence, it is not a standalone cure.​