Acamprosate vs. Naltrexone for Alcohol Use Disorder: 5 Differences You Need to Know About

If you or a loved one has alcohol use disorder (AUD), you know how hard it can be to stop drinking. According to a national survey by the Substance Abuse and Mental Health Services Administration (SAMHSA), about 10% of Americans over the age of 12 had AUD in 2021. But less than 5% received treatment.

Acamprosate and naltrexone (Vivitrol) are first-choice medications to help treat AUD in adults.  But which medication is right for you or a loved one? Here, we’ll look at acamprosate versus naltrexone and five of their major differences.

1. Acamprosate and naltrexone are first-choice options for alcohol use disorder. But they work in different ways.

While we don’t fully understand how acamprosate works, it may be by balancing brain chemicals. The chemical form of acamprosate is similar to gamma-aminobutyric acid (GABA). GABA is a neurotransmitter (chemical messenger) with a brain-calming effect. Long-term alcohol use can decrease GABA levels and increase levels of a chemical called glutamine. By balancing these chemicals, acamprosate may be able to help lower alcohol cravings and keep you from drinking.

Naltrexone works differently than acamprosate. Naltrexone blocks the feel-good effects of alcohol on the body. It does this by blocking the release of certain chemicals, like natural opioids and dopamine. This can make drinking feel less pleasurable.

2. Acamprosate and naltrexone come in different forms and have different dosages

Acamprosate is only available as an oral tablet. In most cases, the dosage is 1 tablet taken 3 times a day.

Naltrexone comes as an oral tablet that’s typically taken once daily. Though, some people may have the option of taking “targeted naltrexone.” This is when naltrexone is taken on an as-needed basis, right before a situation involving a risk of drinking heavily. This method isn’t FDA-approved. But research shows it’s successful for some people, especially heavy drinkers and those who don’t want to abstain completely from alcohol.

Naltrexone also comes as an intramuscular (IM) injection called Vivitrol. You only need it once every 4 weeks, but it has to be given by a healthcare provider. Some people may prefer the injection because it doesn’t require them to take medication by mouth. But others may find it difficult to make it to their provider’s office every 4 weeks and prefer the oral medication.

3. Some people should avoid acamprosate, while others should avoid naltrexone

People with severe kidney disease should avoid acamprosate. In these cases, naltrexone may be a better option.

On the other hand, you should avoid naltrexone if you have severe liver damage. You should also avoid naltrexone if you take opioids regularly or have taken an opioid in the past 7 to 10 days. Taking naltrexone with opioids in your system can lead to opioid withdrawal, which can cause symptoms such as anxiety, diarrhea, and sweating. In these cases, acamprosate may be a better option.

Keep in mind: Your healthcare provider will likely order blood tests to check your kidney and liver function before prescribing you acamprosate or naltrexone. They may also check your blood to make sure there’s no trace of opioids before prescribing naltrexone.

4. There are many factors to consider when choosing to take acamprosate or naltrexone

The American Psychiatric Association (APA) considers acamprosate and naltrexone the two most effective AUD medications. But the decision about which medication to take is based on individual factors. For example, if you’re a smoker, naltrexone may be a good option since it might help you quit smoking as well. Or if you have trouble sleeping, acamprosate may be a better choice.

When comparing acamprosate versus naltrexone, one isn’t clearly better than the other. For example, some research shows that naltrexone is better at treating AUD. But other studies have shown that acamprosate is better at helping people stop drinking. Since the research is mixed, your personal preferences and medical history should be considered when deciding which medication to take. 

No matter what, the best treatment plans for AUD also incorporate non-pharmacological therapy This includes things like support groups and behavioral therapy.

5. Acamprosate and naltrexone have different side effects

Acamprosate and naltrexone are both generally well-tolerated. But there are some differences in their side effects.

Acamprosate side effects

The most common acamprosate side effect is diarrhea. Gas and nausea are also possible.

Serious but rare side effects include depression and suicidal thoughts or actions. So if you notice a change in your mood after starting treatment with acamprosate, let your healthcare provider know right away. 

If you or someone you know is having thoughts of suicide, you’re not alone, and help is available. Call the National Suicide Prevention Lifeline at 988, or text HOME to 741-741 to reach the Crisis Text Line. 

Naltrexone side effects

Nausea is the most common side effect of naltrexone. But taking naltrexone with or after meals might help if you experience stomach upset. You may also experience headaches, dizziness, and tiredness with naltrexone. 

Injection site reactions may also occur with the IM injection, Vivitrol. This can involve redness or swelling. If you experience any reactions after receiving the injection, let your healthcare provider know immediately.

More serious naltrexone side effects include the potential for opioid withdrawal. Opioid withdrawal symptoms — including agitation, sweating, diarrhea — can occur if you start taking naltrexone while opioids are in your system. This is why you should be opioid-free for a minimum of 7 to 10 days before starting treatment with naltrexone.

On the other hand, if you’re already taking naltrexone and you start taking opioids, you may be more sensitive to the effects of the opioids. This can put you at greater risk of an opioid overdose. If you or someone you know struggles with substance use, help is available. Call SAMHSA’s National Helpline at 1-800-662-4357 to learn about resources in your area.

Feeling depressed or having suicidal thoughts can also happen after starting treatment with naltrexone. If you notice a change in your mood while taking naltrexone, talk to your provider.

Can you take acamprosate and naltrexone together for AUD?

A combination of acamprosate and naltrexone for AUD treatment has been studied. In general, the research doesn’t show that combining these medications is more beneficial than taking either medication alone.

It’s also important to keep in mind that combining these medications puts you at risk for both of their individual side effects. And the combination itself may have risks we don’t fully understand. Talk to your healthcare provider if you’re wondering whether taking acamprosate and naltrexone together is a good option for you.

How to save on acamprosate and naltrexone

There are ways to save on acamprosate and naltrexone, including:

• Save with GoodRx. GoodRx may be able to help you save over 70% off the average retail price of the generic versions of acamprosate and naltrexone. At certain pharmacies, the price for generic acamprosate may be as low as $67.82 with a free GoodRx coupon. And the price for generic oral naltrexone may be as low as $39.47 with a free GoodRx coupon.

• Save with a copay savings card. If you have commercial insurance, you may be eligible to save up to $500 a month on out-of-pocket costs for brand-name IM Vivitrol using a savings card from the manufacturer.

Why trust our experts?

Written by:

Daphne Berryhill, RPh

Daphne Berryhill, RPh, has two decades of experience as a clinical pharmacist. She spent most of her career in the Chicago area practicing in-home infusion.

Edited by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed by:

Jonathan Avery, MD

Jonathan Avery, MD, is the current vice chair of addiction psychiatry and an associate professor of clinical psychiatry at Weill Cornell Medical College and New York-Presbyterian Hospital.

Our editorial standards

Meet our experts