this study scrutinized a combination of published and previously undisclosed data from five randomized controlled
, which were evaluated by the Food and Drug Administration for Xanax XR, the brand name for alprazolam.
Alprazolam is a member of the benzodiazepine class of sedatives, extensively prescribed for several decades to address medical issues like
. Notably, in recent times, benzodiazepines have been linked to significant clinical concerns, including dependency, withdrawal symptoms, falls, and cognitive impairment.
“Clinicians are well aware of these safety issues, but there’s been essentially no questioning of their effectiveness,” said senior author Erick Turner, M.D., professor of psychiatry at the Oregon Health & Science University School of Medicine and former FDA reviewer. “Our study throws some cold water on the efficacy of this drug. It shows it may be less effective than people have assumed.”
Turner and co-author Rosa Ahn-Horst, M.D., M.P.H., a resident in psychiatry at Harvard University, reviewed publicly available FDA data from phase 2 and phase 3 clinical trials conducted for extended-release alprazolam for the treatment of panic disorder. The extended-release formulation was approved by the FDA in 2003, while the original immediate-release formulation was approved in 1981.
Revealing Discrepancies: Unpublished Alprazolam Trials and the FDA’s Assessment
They found that five trials had been conducted, but only three of them had been published in medical journals. Further, when the FDA reviewed the drug company’s trial results on how well the drug performed compared with a placebo, Turner said they determined that only one of the five trials had a clearly positive outcome.
Using meta-analysis, a statistical method of combining all study results, they found that alprazolam extended-release was still superior to a placebo, but not as much as the published data had conveyed. Specifically, they found that publication bias inflated the drug’s efficacy by more than 40%.
Turner said the findings may be especially relevant to patients and clinicians who haven’t used benzodiazepines previously, as opposed to those who use the drug infrequently or who have already become physically dependent.
“This study will reinforce being cautious about starting a prescription,” Turner said.