Signal detection between 5-alpha reductase inhibitors and the risk of suicidality and depression: an international pharmacovigilance analysis

<p dir="ltr">Objective: This study aims to investigate the signal detection between the use of finasteride and dutasteride and the occurrence of suicidality, including suicidal ideation, attempts, and completed suicide, as well as the development of depression.</p><p dir="ltr">Methods: This study utilized data from a global pharmacovigilance database encompassing over 35 million adverse event reports from more than 140 countries. Suicidality and depression were defined by MedDRA terms version 26.0. To analyze the data, two well-established pharmacovigilance indicators were applied: the information component (IC) and the reporting odds ratio (ROR).</p><p dir="ltr">Results: A total of 395 and 1299 reports of suicidality and depression, respectively, were identified in signal detection with finasteride and dutasteride. Reporting trends showed that cases first emerged in 1992, with a notable increase after 2010. The main analysis identified signal detections between finasteride use and both suicidality (ROR, 7.28 [95% CI, 6.57–8.06]; IC, 2.82 [IC_0.25, 2.65]) and depression (ROR, 28.18 [95% CI, 26.57–29.89]; IC, 4.68 [IC_0.25, 4.58]), whereas dutasteride showed no significant signal for suicidality and a weaker signal with depression (ROR, 3.23 [95% CI, 2.61–4.00]; IC, 1.66 [IC_0.25, 1.30]). In subgroup analysis, younger individuals (18–44 years) had particularly strong signals for suicidality (IC, 3.54 [IC_0.25, 3.27]), and depression (IC, 5.25 [IC_0.25, 5.05]) associated with finasteride, suggesting a heightened susceptibility in this age group. The time to onset of suicidality and depression was predominantly reported after 3 months of drug administration, with suicidality occurring at an average of 114.92 days and depression at 93.31 days.</p><p dir="ltr">Conclusions: Although our study does not imply causality, this findings suggest a statistically significant disproportionality in reports of suicidality and depression associated with finasteride use and increased signal risks of suicidality and depression highlighting the need for further large-scale epidemiological studies to confirm these findings and investigate the underlying mechanisms.</p>