Summary: Researchers have discovered discrepancies in the efficacy of alprazolam (Xanax XR), a widely prescribed benzodiazepine sedative, when analyzing both published and unpublished clinical trial data.
The study found that only one of the five FDA-reviewed trials showed a clearly positive outcome. Through a meta-analysis, it was unveiled that publication bias might have overstated the drug’s effectiveness by over 40%.
Erick Turner, the senior author, emphasizes the need for caution when prescribing this medication, especially for first-time users.
Key Facts:
- Alprazolam (Xanax XR) efficacy is being called into question after new research analyses.
- Of the five FDA-reviewed trials, only one demonstrated a clearly positive result.
- The drug’s effectiveness might be inflated by over 40% due to publication bias.
Source: Oregon Health and Science University
New research reveals that the nation’s most widely prescribed type of sedative may be less effective than clinicians and scientists have been led to believe, based on publications in medical journals.
The study, which published today in the journal Psychological Medicine, examined both published and unpublished data from five randomized controlled clinical trials reviewed by the Food and Drug Administration for alprazolam, known by the trade name Xanax XR. It is one of a class of sedatives known as benzodiazepines, widely prescribed since the 1970s to treat medical conditions such as anxiety and insomnia.
In recent years, benzodiazepines have been associated with serious clinical risks, including dependence, withdrawal, 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.
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.
About this psychopharmacology research news
Author: Erik Robinson
Source: Oregon Health and Science University
Contact: Erik Robinson – Oregon Health and Science University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Unpublished trials of alprazolam XR and their influence on its apparent efficacy for panic disorder” by Erick Turner et al. Psychological Medicine
Abstract
Unpublished trials of alprazolam XR and their influence on its apparent efficacy for panic disorder
Objective
To test for publication bias with alprazolam, the most widely prescribed benzodiazepine, by comparing its efficacy for panic disorder using trial results from (1) the published literature and (2) the US Food and Drug Administration (FDA).
Methods
From FDA reviews, we included data from all phase 2/3 efficacy trials of alprazolam extended-release (Xanax XR) for the treatment of panic disorder. A search for matching publications was performed using PubMed and Google Scholar. Publication bias was examined by comparing: (1) overall trial results (positive or not) according to the FDA v. corresponding publications; (2) effect size (Hedges’s g) based on FDA data v. published data.
Results
The FDA review showed that five trials were conducted, only one of which (20%) was positive. Of the four not-positive trials, two were published conveying a positive outcome; the other two were not published. Thus, according to the published literature, three trials were conducted and all (100%) were positive. Alprazolam’s effect size calculated using FDA data was 0.33 (CI95% 0.07–0.60) v. 0.47 (CI95% 0.30–0.65) using published data, an increase of 0.14, or 42%.
Conclusions
Publication bias substantially inflates the apparent efficacy of alprazolam XR.
