Most widely prescribed sedative alprazolam may be less effective than published literature would suggest

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. 

Reference:

Ahn-Horst, R., & Turner, E. (2023). Unpublished trials of alprazolam XR and their influence on its apparent efficacy for panic disorder. Psychological Medicine, 1-8. doi:10.1017/S0033291723002830.