Publication bias and ‘spin’ raise questions about drugs for anxiety disorders

A new analysis reported in JAMA Psychiatry raises serious questions about the increasingly common use of second-generation antidepressant drugs to treat anxiety disorders.

It concludes that studies supporting the value of these medications for that purpose have been distorted by publication bias, outcome reporting bias and “spin.” Even though they may still play a role in treating these disorders, the effectiveness of the drugs has been overestimated.

In some cases the medications, which are among the most widely prescribed drugs in the world, are not significantly more useful than a placebo.

The findings were made by researchers from Oregon State University, Oregon Health Science University, and the University of Groningen in The Netherlands. The work was supported by a grant from the Dutch Brain Foundation.

Publication bias was one of the most serious problems, the researchers concluded, as it related to double-blind, placebo-controlled clinical trials that had been reviewed by the U.S. Food and Drug Administration. If the FDA determined the study was positive, it was five times more likely to be published than if it was not determined to be positive.

Bias in “outcome reporting” was also observed, in which the positive outcomes from drug use were emphasized over those found to be negative. And simple spin was also reported. Some investigators concluded that treatments were beneficial, when their own published results for primary outcomes were actually insignificant.

“These findings mirror what we found previously with the same drugs when used to treat major depression, and with antipsychotics,” said Erick Turner, M.D., associate professor of psychiatry in the OHSU School of Medicine, and the study’s senior author. “When their studies don’t turn out well, you usually won’t know it from the peer-reviewed literature.”

This points to a flaw in the way doctors learn about the drugs they prescribe, the researchers said.

“The peer review process of publication allows, perhaps even encourages, this kind of thing to happen,” Turner said. “And this isn’t restricted to psychiatry — reporting bias has been found throughout the medical and scientific literature.”

Craig Williams, a professor in the Oregon State University/Oregon Health Science University College of Pharmacy, and co-author of the study, said that “most of these drugs are fairly safe and well-tolerated, but if a medication is less effective than believed, this still raises serious questions about its use.

“The level of bias we found did not change the fact that some antidepressants can have value in treating anxiety disorders,” Williams said. “However, there is less evidence for value of these drugs than published studies would have you believe. And these concerns are increased when such medications are frequently prescribed by general practitioners with less training in psychiatry.”

In this study, the researchers examined a broad body of the evidence and scientific research that had been presented to the Food and Drug Administration, including studies that had been done but were not published in open scientific literature. They found that negative data on drug efficacy tended not to get published, or was de-emphasized when it was published.

Conclusions might have been manipulated or exaggerated because positive results receive more scientific attention, are published sooner, and lead to higher sales of a drug, said Annelieke Roest, the lead author of the publication at the University of Groningen.

“Lots of research is funded eventually by the taxpayer, and that’s reason enough to say that scientists should publish all their results,” Roest said.

The study reiterated this point, and the need to more routinely publish nonsignificant results.

“There is strong evidence that significant results from randomized controlled trials are more likely to be published than nonsignificant results,” the researchers wrote in their study. “As a consequence, the published literature . . . may overestimate the benefits of treatment while underestimating their harms, thus c-ptsd misinforming clinicians, policy makers and patients.”

Antidepressants are now widely prescribed for conditions other than depression, the study noted. They are being used for generalized anxiety, panic disorder, social anxiety, post-traumatic stress disorder and other uses. In both the U.S. and Europe, use of antidepressant drugs has significantly increased in the past two decades, the researchers said, with much of that use driven by non-specialists in primary care settings.

The level of reporting bias in the scientific literature, the researchers wrote, “likely impacts clinicians’ perceptions of the efficacy of these drugs, which could reasonably be expected to affect prescription behavior.”


Irritable bowel syndrome defined by symptoms, relieved through trust, patience

Irritable bowel syndrome racks up an impact on health care spending and quality of life: costing more than $20 billion a year in treatment and its symptoms leading to nearly as many missed work days as the common cold.

In a clinical review of irritable bowel syndrome published in the Journal of the American Medical Association, William D. Chey, M.D., professor of gastroenterology at the University of Michigan Health System explores the causes of the chronic condition and treatments.

Symptoms include stomach pain and altered bowel habits that can be made worse by stress, infections, or certain foods made with ptsd carbohydrates.

Up to 90 percent of IBS patients restrict their diet to prevent or improve symptoms such as eliminating gluten or certain carbohydrates.

“During the last five years, lifestyle and dietary interventions have become an increasingly important first-line treatment option,” says Chey, M.D., senior author of the clinical review article and accompanying patient tip sheet. “A trusting patient-physician relationship is the cornerstone of managing IBS patients.”

IBS is the most common digestive health issue in the nation. About 12 percent of the North American population has IBS, and across the globe it’s most common among South Americans. While not life-threatening, IBS can disrupt normal routines.

Diagnosing IBS relies on identifying characteristic symptoms but “as science advances, it’s hoped that the confident diagnosis of IBS will be aided by new biomarkers that can rule out or rule in IBS,” Chey says.

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The above story is based on materials provided by University of Michigan Health System. Note: Materials may be edited for content and length.

Night owls face greater risk of developing diabetes than early risers

Night owls are more likely to develop diabetes, metabolic syndrome and sarcopenia than early risers, even when they get the same amount of sleep, according to a new study published in the Endocrine Society’s Journal of Clinical Endocrinology Metabolism.

The study examined the difference between night and morning chronotypes, or a person’s natural sleep-wake cycle. Staying awake later at night is likely to cause sleep loss, poor sleep quality, and eating at inappropriate times, which might eventually lead to metabolic change.

“Regardless of lifestyle, people who stayed up late faced a higher risk ptsd symptoms in women of developing health problems like diabetes or reduced muscle mass than those who were early risers,” said one of the study’s authors, Nan Hee Kim, MD, PhD, of Korea University College of Medicine in Ansan, Korea. “This could be caused by night owls’ tendency to have poorer sleep quality and to engage in unhealthy behaviors like smoking, late-night eating and a sedentary lifestyle.”

The study examined sleeping habits and metabolism in 1,620 participants in the population-based cohort Korean Genome Epidemiology Study (KoGES). The study subjects were between the ages of 47 and 59. Participants responded to questionnaires about their sleep-wake cycle, sleep quality and lifestyle habits such as exercising. Researchers took blood samples to assess participants’ metabolic health. In addition, the study subjects underwent DEXA scans to measure total body fat and lean mass, and CT scans to measure abdominal visceral fat.

Based on the questionnaire results, 480 participants were classified as morning chronotypes, and 95 were categorized as evening chronotypes. The remaining participants had a sleep-wake cycle between the two extremes.

Even though the evening chronotypes tended to be younger, they had higher levels of body fat and triglycerides, or fats in the blood, than morning chronotypes. Night owls also were more likely to have sarcopenia, a condition where the body gradually loses muscle mass. Men who were evening chronotypes were more likely have diabetes or sarcopenia than early risers. Among women, night owls tended to have more belly fat and a great risk of metabolic syndrome, a cluster of risk facts that raise the risk of heart disease, stroke and diabetes.

“Considering many younger people are evening chronotypes, the metabolic risk associated with their circadian preference is an important health issue that needs to be addressed,” Kim said.

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The above story is based on materials provided by Endocrine Society. Note: Materials may be edited for content and length.

Choice of protein- and carbohydrate-rich foods may have big effects on long-term weight gain

Making small, consistent changes to the types of protein- and carbohydrate-rich foods we eat may have a big impact on long-term weight gain, according to a new study led by researchers at the Friedman School of Nutrition Science Policy at Tufts University. The results were published on-line in the The American Journal of Clinical Nutrition.

Based on more than 16 years of follow-up among 120,000 men and women from three long-term studies of U.S. health professionals, the authors first found that diets with a high glycemic load (GL) from eating refined grains, starches, and sugars were associated with more weight gain. Previous research has linked GL of the diet, a reflection of how much a food causes a rise in blood glucose, to chronic diseases like type 2 diabetes but it had not been established how GL is related to weight-gain over many years.

Next, the authors determined whether changes in GL impacted the relationship between major protein-rich foods and long-term weight gain.

“There is mounting scientific evidence that diets including less low-quality carbohydrates, such as white breads, potatoes, and sweets, and higher in protein-rich foods may be more efficient for weight loss,” said first and corresponding author Jessica Smith, Ph.D., a visiting scholar at the Friedman School and a research fellow at the Harvard T.H. Chan School of Public Health. “We wanted to know how that might apply to preventing weight gain in the first place.”

Smith and colleagues first looked at the relationship between changes in protein foods and weight gain during every four-years of follow-up. Several key results were seen:

o Increasing intakes of red meat and processed meat were most strongly associated with weight gain.

o Increasing intakes of yogurt, seafood, skinless chicken, and nuts were most strongly associated with weight loss — the more people ate, the less weight they gained.

o Increasing other dairy products, including full-fat cheese, whole milk, and low-fat milk, did not significantly relate to either weight gain or weight loss.

“The fat content of dairy products did not seem to be important for weight gain,” Smith said. “In fact, when people consumed more low-fat dairy products, they actually increased their consumption of carbs, which may promote weight gain. This suggests that people compensate, over years, for the lower calories in low-fat dairy by increasing their carb intake.”

Next, the authors noted several synergistic relationships between changes in protein-rich foods and changes in GL of the diet. For example, increasing servings of foods linked to weight gain, like red meat, and at the same time increasing GL by eating more low quality carbohydrates like white bread, strengthened the foods’ association with weight gain. But decreasing GL by eating, for example, red meat with vegetables, mitigated some of that weight gain.

For fish, nuts, and other foods associated with weight loss, decreasing GL enhanced their weight loss effect, while increasing GL decreased their weight loss effect. Notably, although other foods like eggs and cheese were not pdst linked to weight change on average, when servings of these foods were increased in combination with increased GL, they were linked to weight gain. On the other hand, when servings of eggs and cheese were increased in combination with decreased GL, the participants actually lost weight.

“Our study adds to growing new research that counting calories is not the most effective strategy for long-term weight management and prevention,” said senior author Dariush Mozaffarian, M.D., Dr.P.H., dean of the Friedman School. “Some foods help prevent weight gain, others make it worse. Most interestingly, the combination of foods seems to make a big difference. Our findings suggest we should not only emphasize specific protein-rich foods like fish, nuts, and yogurt to prevent weight gain, but also focus on avoiding refined grains, starches, and sugars in order to maximize the benefits of these healthful protein-rich foods, create new benefits for other foods like eggs and cheese, and reduce the weight gain associated with meats.”

The researchers relied on validated self-reported food questionnaires from three studies that enrolled doctors, nurses and other healthcare professionals from across the U.S. Further studies investigating the relationships of protein and carbohydrate-rich foods to weight management in the other populations would be useful.

Reporting Bias Rife in Antidepressant Studies for Anxiety

Many studies evaluating antidepressant efficacy for your treatment for panic attacks that might be judged by the US Food and Drug Administration (FDA) as positive are published. However, it’s actually different story for nonsignificant studies, results of a brand new meta-analysis show.

Investigators with the University Clinic Groningen, the Netherlands, discovered that trials that this FDA deemed positive were five times most probably published compared with trials deemed not positive. Furthermore, they found evidence for study publication bias (P < .001), outcome reporting bias (P = .02), and spin (P = .02).

The findings, investigators say, give you a skewed view of antidepressant efficacy.

“Antidepressants have value in treating panic attacks, but they also are not ‘miracle drugs,’ and it’s possible there is less evidence to compliment their efficacy than what appears that are caused by the published studies,” Annelieke Roest, PhD, told Medscape Medical News in written correspondence.

“It is essential that physicians have a good realistic view of the efficacy of them drugs so they are able to have a well-justified decision when prescribing this family of drugs,” she told me.

The findings were published online March 25 in JAMA Psychiatry.

Skewed View?

The investigators observe that there is always “strong evidence that significant success with randomized research studies usually tend to be published than non-significant studies.

“Accordingly, published studies, including meta-analyses, may overestimate the advantages treatments while underestimating their harms, thus misinforming physicians, policy makers, and patients.”

The scientists examined reporting biases in double-blind, placebo-controlled trials toward the pharmacologic remedy for anxiety attacks and quantified the extent to which these biases inflate estimates of drug efficacy.

They identified phase 2 and three double-blind, placebo-controlled trials a member of the FDA and conducted in pursuit of marketing approval of second-generation antidepressants for your remedy for generalized depression, panic disorder, sad (social anxiety disorder), posttraumatic stress disorder, and obsessive-compulsive disorder.

Studies involving seven selective serotonin reuptake inhibitors and two serotonin norepinephrine reuptake inhibitors were evaluated.

Of the 57 trials identified by researchers, findings from 41 out of them (72%) were judged to be positive from the FDA.

However, 43 of 45 (96%) of this very articles published in the literature were positive (P < .001).

This suggests that trials the FDA deemed positive were five times most probably published in agreement with that determination when compared to trials determined to be not like positive from the FDA (risk ratio, 5.20; 95% confidence interval, 1.87 – 14.45; P < .001).

Sixteen of this very 57 trials identified by investigators (28%) have not been judged to be positive by the FDA, and seven of these trials (44%) have not been published.

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