Unraveling the Distinct Adverse-Event Profiles of Finasteride Versus Tamsulosin for Benign Prostatic Hyperplasia and Causal Links to Psychiatric Disorders Using Faers Pharmacovigilance and Mendelian Randomization

Abstract

Background: Treatments for Benign Prostatic Hyperplasia (BPH) commonly include 5-alpha reductase inhibitors and alpha-1 blockers, but their safety profiles differ.

Methods: We systematically queried the Food and Drug Administration Adverse Event Reporting System (FAERS) for cases associated with finasteride and tamsulosin. Disproportionality analyses evaluated the Reporting Odds Ratio (ROR) and Information Component (IC). Afterwards, two-sample Mendelian randomisation (MR) was utilised to verify causal links between testosterone levels and Major Depressive Disorder (MDD).

 
Findings: The FAERS analysis included 1800 unique patients, where finasteride generated robust positive pharmacovigilance signals for psychiatric disorders and decreased libido. Tamsulosin was disproportionately associated with vascular events and orthostatic hypotension. The MR analysis confirmed that genetically predicted circulating testosterone levels exhibited an inverse causal trajectory directly aligned with the risk of developing MDD. 

Interpretation: Finasteride and tamsulosin display markedly different safety spectra. The psychiatric signals observed with finasteride in FAERS are causally supported by androgenic alterations demonstrated through MR.