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Recruitment Method Sells Anxiety Drug Trials Short

University of Otago psychiatrists have warned that some medications used to treat anxiety may appear ineffective because they are not being tested in appropriate patients.

Dr Chris Gale and Prof Paul Glue wanted to investigate why there is such a variation in the results of placebo-controlled trials of benzodiazepines used to treat severe anxiety and sleep problems, so they reviewed studies of 5400 participants between 1977 and 2013. They found that in the earlier years the trials involved people with more severe anxiety, while the newer trials relied on recruiting participants from advertisements, and some of these people had less severe anxiety and often responded just as well to placebos as the drug.

Gale says that most of the variation in the effectiveness of benzodiazepines, such as Valium, related to the severity of anxiety before treatment. Another factor was the length of the trial – longer trials had less effect. This finding is expected since patients develop tolerance to benzodiazepines over time.

Older trials generally involved people with severe anxiety, including some who were hospitalised, while many newer trials involved recruiting study participants from the community by newspaper advertisements and social media. “This newer population may not be the same as the patients we see clinically, in that their anxiety may be much less severe,” Gale explains. “Placebos appear to work as well as benzodiazepines in this less severely affected patient group. However, in the more severe group, benzodiazepines are superior.”

While benzodiazepines are still currently widely used, Gale says the results have a concerning implication. “We may be using the wrong population to test medications. This community-recruited group, particularly in psychiatry, may be giving us a false result that useful medications are no better than placebo.”

Gale says that to ensure appropriate information is collected about the use of benzodiazepines, he would advocate recruiting people for testing who are either receiving treatment or in need of treatment for psychiatry or pain-related conditions. It may also mean that a large number of trials, particularly for anxiety disorders, need to be reanalysed to take into account the severity of anxiety.

The study was published in the Journal of Psychopharmacology (