Naltrexone VS Acamprosate: Which Drug to Combat Alcoholism and When?

When it comes to stopping drinking, many different circumstances exist. Maybe it’s time to quit drinking. Maybe you’re drinking too heavily too often and you want to cut it back to a normal level. Maybe you’ve been clean for some time but you’re having cravings for alcohol. These are three completely different circumstances, and each should be handled in its own way.

So where do you turn? Your most likely first step is to enter yourself into an alcohol abuse treatment program. During this process, it’s almost guaranteed that medication assisted treatment will be an option. Only three FDA-approved drugs exist to combat alcoholism: naltrexone, acamprosate, and disulfiram. However, in the medical field, much debate exists as to which drug to use and under what circumstance.

(Note: Disulfiram strictly causes the body to respond negatively to alcohol. Drinking with disulfiram in the system produces a multitude of hangover-like effects, and is only used as a physical deterrent. In different ways, both naltrexone and acamprosate are used to reduce craving, block the effects of drinking, and ultimately lead to abstinence or responsible drinking. Therefore, in this article, disulfiram is minimally focused on.)

Determining which Medication to Use

In 2013, UK-based Drug & Alcohol Findings (DAF) performed an analysis of forty years’ worth of scientific studies regarding the naltrexone/acamprosate debate. The results have just recently been published. What this means is the DAF research team reviewed countless studies on each drug, all performed between 1970 and 2009. The team sought to find “which is best in which circumstances and for which treatment goals.”

In this article, we will compare the alcohol-dependence medications naltrexone and acamprosate, in order to establish a knowledge base. Then we will review the findings of the DAF analysis, regarding which medication to use and under which circumstance. Finally, we will discuss the current use of both medications, some alternatives, and the best overall methods of alcohol treatment per circumstance.

What are Naltrexone and Acamprosate?

Naltrexone blocks opioid receptors in the brain. This causes the effects of opioids such as heroin or OxyContin to be prevented and/or reversed. Such drugs are called opioid antagonists. It turns out that opioid antagonists are excellent at decreasing alcohol consumption, as reinforced by an Oxford study. What’s more, naltrexone “is probably the most thoroughly scientifically established adjunct in the alcoholism treatment field,” as quoted from the study. Naltrexone is sold under the brand names of Revia, Depade, and Vivitrol.

Acamprosate essentially resets the chemical imbalances caused by problematic drinking. Among many other things, alcohol abuse leads to an overabundance of dopamine in the brain. Dopamine is a chemical produced by the brain that reinforces rewarding behavior, such as eating, exercising, or having sex, by creating feelings of joy. With prolonged alcohol abuse, the brain becomes used to extra dopamine, and eventually the drinker cannot feel that joy without alcohol.

This is the short story of what prolonged alcohol abuse does to your brain, and only one aspect of it. Multiple chemical imbalances occur in the brain because of alcohol abuse, and acamprosate can “restore the normal activity of glutaminergic neurons, which become hyperexcited as a result of chronic alcohol exposure,” according to the National Library of Medicine. Now, that’s a mouthful for laymen like yours truly, but basically this means acamprosate restores the balance of a pre-alcohol-soaked brain.

So, while naltrexone blocks the effects of alcohol and reduces the craving for it, acamprosate resets the brain’s balance and promotes abstinence from alcohol.

The Drug & Alcohol Findings Study

The question remains of which medication to use and when. The Drug & Alcohol Findings (DAF) study, linked again here, determined just that. First and foremost, the researchers tested each medication against a placebo. Both were found to work much better than the placebo, and therefore both are legitimate treatments for alcohol abuse. What they discovered next contradicted previous knowledge regarding naltrexone and acamprosate.

Previously, three major-scale studies had been performed to determine when to use which of the two drugs. The first study, in 2003, found little difference between them, giving naltrexone “a slight edge in delaying a return to drinking…,” as stated in the DAF study. The second study, in 2006, concluded both drugs to be virtually ineffective, finding “no significant effects of either medication compared with a placebo…” and the third study, also in ’06, determined naltrexone to be more effective when accompanied by psychosocial therapy, such as by a treatment facility. The opposite was found for acamprosate.

Obviously these conclusions are all very different. The DAF researchers believe they have once and for all determined a correct conclusion. According to their study, “naltrexone should be considered for patients who want less often to drink heavily, while acamprosate is better for those who seek abstinence.” Furthermore, both medications are more effective for those who are detoxified of alcohol.

Perhaps nothing revolutionary has been discovered here, due to the fact that both medications are fairly safe. However, the results of the DAF study help narrow down which path to take according to circumstances. The results will quicken the process of medication assisted treatment for alcohol abuse.

The Results for Naltrexone

Prior to the DAF study, it was commonly believed that naltrexone and acamprosate were nearly interchangeable. This is not so. Naltrexone benefits those seeking to cut back their current drinking, whether aiming for abstinence or not. Also believed before this study was that naltrexone can and even should be taken by patients who are still drinking. However, “required abstinence before treatment was associated with greater abstinence during treatment and greater reductions in heavy drinking.”

In further contrast to popular belief, the DAF study found that naltrexone is less effective as part of an alcohol abuse treatment program if abstinence is the main goal. In other words, if naltrexone is to be used as part of a treatment program, it is more effective when the program does not focus on abstaining from drinking.

The Results for Acamprosate

Before the DAF study, acamprosate was considered to be inferior to naltrexone. However, if a patient’s situation calls for complete abstinence as opposed to curbing drinking, acamprosate is preferred. Also, similarly to naltrexone, it is best if a patient is detoxified from alcohol when using acamprosate. “Both seem more effective when participants are detoxified and abstinent when treatment begins,” says the DAF study.

It was also noted that in the case of acamprosate, it’s possible “these requirements [of abstinence] filter out less committed and motivated drinkers, leaving a sample more likely to comply with treatment…” This is not the case with naltrexone, since it has for decades been given to patients who continue drinking alcohol regularly.

Regarding using acamprosate as part of an alcohol abuse treatment program, the results are the same as with naltrexone. No clear evidence was found to suggest that psychosocial therapy improves or worsens its effects. However, there is a slight lean toward psychosocial therapy actually weakening both medications’ effects. As stated in the DAF study, “…neither medication needs therapy to succeed,” adding that both medications may work better “when not overshadowed by effective psychosocial approaches.”

Current Uses (and their Necessary Updates)

The current status of naltrexone is best summarized by Dr. Stewart Leavitt of SAMHSA, or the Substance Abuse and Mental Health Services Administration: “In brief, naltrexone is significantly beneficial in helping those patients who cannot remain abstinent to reduce their drinking behaviors, breaking the vicious, self-destructive cycle in alcoholics whereby one drink leads to another, and allowing more quality time for psychosocial therapy to be productive.”

However, the DAF study has revealed that naltrexone may be more effective when separated from therapy, and is very likely to be more effective when used by a detoxified patient.

The current status of acamprosate is not as straightforward. It is widely believed that more research must be done on the medication. However, acamprosate is being used. According to an article by Dr. Bankole Johnson published on UpToDate, acamprosate is able “to reduce alcohol consumption compared with placebo in patients with alcohol dependence.” The major difference is how acamprosate achieves this. Yes, the drug seems to rebalance the brain’s chemicals post-alcohol abuse, but as written in the Substance Abuse Treatment Advisory published by SAMHSA, “Although acamprosate’s mechanism of action has not been clearly established, it may work by reducing symptoms of postacute (protracted) withdrawal, such as insomnia, anxiety, and restlessness.”

However, the DAF study shows that acamprosate “has a better record at promoting abstinence than naltrexone,” and is much less effective at reducing craving. As opposed to using acamprosate to reduce alcohol consumption, patients are better off using it once they are detoxified, in order to balance the brain. The medical community knows acamprosate does this, but still isn’t 100% clear how.

What this Suggests

As mentioned before, only three medications are FDA-approved for use in combating alcohol abuse. Aside from naltrexone and acamprosate, there is disulfiram, which if you remember is basically a physical deterrent from alcohol. If you have disulfiram in your system and you consume alcohol, a list of unpleasant things begins happening to you. Due to its blatant effects, disulfiram is a much simpler medication than naltrexone or acamprosate. The use of disulfiram is a common option, and is very different from the other two medications. Regarding naltrexone and acamprosate, what the DAF study truly uncovered was a paradox.

The study provided more specific uses than previously realized for the medications. Simultaneously, the study showed that “there is no evidence-based way to tell which drug will work best for an individual patient, or if any will help at all.” As a matter of fact, only “1 in 7 or 1 in 8 trial participants would not benefit more than when prescribed an inactive placebo.” This means there is good news and bad news. The good news is that there are now more effective ways to use naltrexone and acamprosate. The bad news is obvious. Utilizing medication assisted treatment may still be a bit of a guessing game for a while.

Just because the DAF study found psychosocial therapy ineffective when combined with medication does not mean the practice should be stopped. After all, in the words of the study itself, “Despite contrary findings… it remains possible that in terms of absolute improvements, supplementing medication with therapy will gain the best outcomes for a patient.”

The Best Choice for You

Frankly, what’s best for you is up to you. There are several options. Seeking entry into an addiction treatment facility is always your best bet. There, you have all of your options open to you. Medication assisted treatment or not, the help received through a recovery program is invaluable. That being said, what options are there regarding medication, and should you or shouldn’t you accompany them with therapy?


The above chart is provided by Drug and Alcohol Findings as part of a series on Naltrexone. Although the most successful method is using both medications at once with no therapy, none of the methods fall below a 55% success rate. However it cannot be ignored that use of a placebo is the least successful method.

It boils down to a personal choice. Whichever method works best for you, stick to it. Some people might not require psychosocial or psychological therapies in order to sober up, but medication seems to help all recovering alcoholics.

The bottom line is that detoxification is an absolute requirement. Whether you aim for abstinence or responsible drinking, if you are abusing alcohol and want to stop, you must detox. If anything, the DAF study has reinforced this.