Author Insights: Medications Help Curb Alcohol Use Disorders

Daniel E. Jonas, MD, MPH, of the University of North Carolina at Chapel Hill, and colleagues found drugs that help individuals with alcohol use disorders abstain from drinking.  Image: Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill

Daniel E. Jonas, MD, MPH, of the University of North Carolina at Chapel Hill, and colleagues found drugs that help individuals with alcohol use disorders abstain from drinking. Image: Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill

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.

Author Insights: Treating Mental Stress May Benefit Patients With Coronary Heart Disease

Wei Jiang, MD, of Duke University Medical Center in Durham, NC, and colleagues found treating patients with coronary heart disease with medication reduced the risk of episodes of mental stress–induced myocardial ischemia. (Image: Duke Medicine)

Wei Jiang, MD, of Duke University Medical Center in Durham, NC, and colleagues found treating patients with coronary heart disease with medication reduced the risk of episodes of mental stress–induced myocardial ischemia. (Image: Duke Medicine)

Mental stress can potentially trigger an episode of myocardial ischemia, a decrease in the flow of oxygen-enriched blood to the heart muscle caused by the narrowing of coronary arteries, resulting in chest pain and more serious events such as heart attack in patients with coronary heart disease. A small study appearing today in JAMA finds that treating such patients with a specific type of antidepressant can lower the rate of mental stress–induced myocardial ischemia.

The study by researchers from Duke University Medical Center in Durham, NC, randomly assigned 112 patients to receive either placebo or the selective serotonin reuptake inhibitor escitalopram (Lexapro), an antidepressant that is also used to treat anxiety. At the end of 6 weeks, 34.2% of patients taking escitalopram had an absence of mental stress–induced myocardial ischemia during 3 mental stressor tasks (such as performing mental arithmetic) compared with 17.5% of patients taking placebo.

Lead author Wei Jiang, MD, from Duke’s Department of Medicine, discusses her team’s findings and clinical implications.

news@JAMA: What do your results tell you about the link between mental stress and the heart?

Dr Jiang: Emotional modulation with medication does improve mental stress–induced myocardial ischemia. However, the effect size is moderate and not as high as I had originally thought. But I have to say that 6 weeks on treatment is rather short, and patients may need to be on the medication a longer time.

news@JAMA: Do cardiologists actively treat mental stress?

Dr Jiang: Mental stress–induced myocardial ischemia has not been well received in the cardiovascular field, although its presence has been known for a number of years. I hope our results will facilitate the higher recognition that mental stress–induced myocardial ischemia is a common problem and treatable.

news@JAMA: Are you suggesting cardiologists medicate these patients for years to reduce mental stress?

Dr Jiang: I wouldn’t highly promote taking medication, period. For us, this was more of a proof-of-concept study showing that medication does work. At the same time, physicians and patients need to work together to see what would be the most practical treatment for this condition. Is it exercise, stress management, or taking a pill? I would suggest that patients with coronary heart disease get tested for mental stress–induced myocardial ischemia and, if they have it, engage in aerobic exercise and stress-reduction therapy and then be tested 3 months later. If they still have it, then consider medication.

Class of Drugs Widely Prescribed for Insomnia and Anxiety Associated With Increased Risk of Fatal Pneumonia

Researchers found an association between benzodiazepine use and increased risk of and death from pneumonia. (Image: WILLSIE/iStockphoto.com)

Researchers found an association between benzodiazepine use and increased risk of and death from pneumonia. (Image: WILLSIE/iStockphoto.com)

Benzodiazepines, a commonly prescribed class of drugs used for treating insomnia, anxiety, and other conditions, may also increase a person’s risk of contracting and dying from pneumonia. Patients who were taking these drugs or had taken them in the past were 54% more likely to contract pneumonia, 22% more likely to die within 30 days of being diagnosed with pneumonia, and 32% more likely to die within 3 years of diagnosis compared with individuals not taking the medications. The findings, by researchers from England, appear today in the journal Thorax.

Specifically, the researchers found that Valium, Ativan, and Restoril, but not Librium, were associated with increased incidence of pneumonia. All 4 medications, individually, were associated with increased long-term risk of death. Continue reading

Early Marriage Has Lasting Consequences on Women’s Mental Health

A new study finds that women who marry before the age of 18 years are more likely to experience mental health problems. (Image: Charity Myers/iStockphoto.com)

Marriage before the age of 18 years, often termed child marriage, increases a woman’s chance of developing a psychiatric condition in her lifetime and also increases the likelihood she will receive care for such a disorder, according to a study published today in the journal Pediatrics.

Child marriage is often associated with developing countries where prevalence rates of 40% to 50% are not uncommon and child brides may face life-threatening health issues such as serious obstetric complications, including fistula. But marriage of adolescent girls also remains a persistent issue in the United States and other industrialized countries. Continue reading

New Chemical Pathway May Explain Abnormal Stress Responses

A newly discovered novel chemical pathway that affects the neurons in a part of the brain that is linked to fear responses could ultimately lead to treatments and possible prevention of stress-related disorders. (Image: University of Leicester)

A previously unknown chemical pathway in the brain may explain why some individuals are more susceptible to stress-associated psychiatric disorders such as depression, anxiety, and posttraumatic stress disorder, suggest findings from research in a mouse model. If confirmed in human studies, the discovery could lead to new targeted therapies for and possibly prevention of these disorders. The report, by researchers from the University of Leicester in England in collaboration with investigators from Poland and Japan, appears today in Nature.

Some of the estimated 20% of individuals who experience some form of anxiety disorder at least once in their lives are more susceptible than others to the detrimental effects of stress. This variability in susceptibility piqued the researchers’ curiosity. “We asked: What is the molecular basis of anxiety in response to noxious stimuli? How are stress-related environmental signals translated into proper behavioral responses?” said Robert Pawlak, MD, PhD, of the University of Leicester, in a release. “This resulted in the discovery of a critical, previously unknown pathway mediating anxiety in response to stress.” Continue reading