Quitting drinking can be a difficult task for individuals with alcohol use disorders, but a pair of drugs may help, finds an analysis of more than 100 studies examining the use of medications to treat these conditions.
Alcohol use disorders are common in the United States, affecting an estimated 17 million people in the United States. These disorders have severe consequences for patients’ health, contributing to increased cancer risk, liver disease, and other health problems. Individuals with these disorders may also face steep social and economic costs, including job loss or family estrangement. Yet, less than one-third are ever treated and only 10% take medication for the conditions, despite a large body of evidence on the effectiveness of these interventions.
Lead author Daniel E. Jonas, MD, MPH, of the University of North Carolina at Chapel Hill, explained that sometimes having a large body of evidence on numerous drugs can create confusion about what works and what doesn’t. To provide clearer information about the benefits and harms of the available medications, he and his colleagues reviewed data from 122 randomized clinical trials and 1 cohort study involving a total of 22 803 participants. The studies were, on average, 12 weeks long. They found that either oral naltrexone or acamprosate helped patients refrain from drinking. To prevent 1 person from resuming drinking, 12 patients would have to be treated with acamprosate (the number needed to treat) or 20 would have to be treated with oral naltrexone. Treatment with oral naltrexone also helped reduce the risk of a return to heavy drinking, with 1 patient benefiting for every 12 treated. Injectable naltrexone was associated with reduced drinking days, but not abstinence.
Jonas discussed the findings with news@JAMA.
news@JAMA: What do the numbers needed to treat tell us?
Dr Jonas: We have to treat 12 people with naltrexone to get 1 to successfully reduce drinking. People look at that 2 ways—some may not view it as very good, but those numbers are pretty good compared with other medications that have wide support.
news@JAMA: Are physicians using medications to treat alcoholism?
Dr Jonas: No. These treatments are underused and there’s a lot of room for improvement. Most primary care physicians—I’m a primary care physician—are trained to refer people with alcohol use disorders to specialists. They are not really trained to treat them by providing psychosocial interventions or medicine. Many communities don’t have specialist care that physicians can refer patients to.
news@JAMA: Do you have any explanation for why the results would be different for oral or injectable naltrexone?
Dr Jonas: There are some pharmacokinetic reasons why it may not work when you convert the drug to an injectable. It’s also monthly, there’s a lot of challenges in getting a drug to last for a month. But there is not yet that much evidence on the injectable. It’s possible additional studies will show the injectable form may work.
news@JAMA: Why might acamprosate reduce the risk of having a drink but not of a return to heavy drinking?
Dr Jonas: I don’t know the answer. Some theories are tied to the mechanism of action. Naltrexone reduces craving, while acamprosate works on through other mechanisms. There’s some thinking naltrexone may be better for preventing a return to heavy drinking, but acamprosate is better for avoiding drinking.
news@JAMA: How do the results for naltrexone and acamprosate compare with disulfiram?
Dr Jonas: Disulfiram has been around the longest. Well-controlled studies don’t really show that it works. There are fewer good studies of disulfiram. When you look at naltrexone or acamprosate we have more and better evidence.
news@JAMA: What did you learn about adverse effects and tolerability?
Dr Jonas: The evidence on harms wasn’t as good as evidence on benefits. A number of adverse events are slightly increased compared with placebo for the 2 drugs. Acamprosate was a most commonly associated with anxiety, diarrhea, and vomiting. Naltrexone was associated with a higher risk of dizziness, nausea, and vomiting.
news@JAMA: Are there any other cost or convenience differences between the 2 drugs?
Dr Jonas: Everyone wants to know how to pick which drug to use. Naltrexone is 1 pill once a day. Acamprosate is 2 pills 3 times a day. It’s really hard for anyone to take 2 pills 3 times a day reliably. So unless the patient has a contraindication, many physicians will try naltrexone first. Both are available in generic. Wholesale naltrexone is cheaper. Injectable naltrexone is the only one with a high cost, about $1200 a month.
news@JAMA: Which of the off-label treatments have the strongest evidence base favoring effectiveness?
Dr Jonas: Just 2 had moderate effects, topiramate and nalmefene. Nalmefene is approved in other countries; it is similar to naltrexone. There is not as much evidence for either of these as for naltrexone and acamprosate.
Topiramate is a really used for a lot of off-label things. It has adverse effects that can lead to cognitive dysfunction, paresthesia, and taste abnormalities. It has a long list of common adverse effects.
news@JAMA: What do you think is the main take-home message?
Dr Jonas: We have some medicines that can be a useful component of treatment. These are so underused. The related question, is whether primary care needs to start doing more treatment rather than referring. There just isn’t an adequate supply of specialists who take care of people with alcohol use disorders.
Additionally, there are barriers to getting to a specialist and people may not want to go. Lots of patients with alcohol use disorders have comorbid depression and anxiety that often prevents them from seeing another physician they don’t know.