Investigation of Suicidality and Psychological Adverse Events in Patients Treated With Finasteride
Nguyen et al,. 2020
“we found significant disproportional signals for suicidality associated with finasteride use. In stratified analyses, these signals were not present in older patients prescribed finasteride for BPH but were only present among younger patients using finasteride for alopecia.”
VigiBase is the World Health Organization’s international database of individual case safety reports. Using validated methods to analyse VigiBase data, significant disproportional signals for suicidality and psychological adverse events were associated with finasteride use in young men using the drug for hair loss. This was not seen in older patients using the drug for urological treatment.
No such signal was associated with drugs that had different mechanisms of action but similar indications or with drugs that had similar mechanisms and adverse effect profiles, suggesting that alopecia itself is not likely an explanation for increased suicidality.
They considered their findings suggestive that the high rate of suicidality and psychological adverse events in association with finasteride use could potentially be attributed to unique characteristics of the drug in young patients with alopecia.
PFSNetwork comment
We thank the authors for the important data presented as part of this report.
As organising members of the largest PFS patient platform, propeciahelp, we stated in our 2020 literature review that PFS is more common in younger men taking lower dose for hair loss than older men using for BPH. Alongside further FAERS record analysis showing multidomain symptoms to be more severe and frequent in younger men using 1mg finasteride, this data shows that suicidality and psychological adverse event records support our observation and data.
The authors speculate that, as dutasteride has similar pharmacologic properties and adverse effects as finasteride and is prescribed for the same indications, adverse event reports would be expected to be the same and so attention from the media may underlie increased reporting of suicidality associated with finasteride. However, it is important to note that dutasteride is approved for use for hair loss in only a small number of countries, not including the USA. Users of dutasteride are therefore likely to be much older averagely. A large cohort study, mentioned by the authors as a finding at odds with their own, determined no significant difference in suicidality between the two drugs. Crucially, that cohort was aged 66 or above exclusively.
We alternatively suggest that age is a contributory factor in predisposition to harm arising from antiandrogenic endocrine disruption, as opposed to specific 5ari product.
Future studies should account for multiple lines of information suggesting PFS and associated adverse events primarily occur in younger men using the drug for hair loss.
In late adolescent rats, finasteride remarkably decreases the activity of the dopaminergic system, exploratory and motor behaviours through decreasing DHT production and consequently androgen receptor activation on dopamine neurons in the substantia nigra and ventral tegmental area.
Interestingly, this effect was not seen in older or younger rats (Li et al., 2017). The reported reduction in brain DHT of late adolescent rats had not been observed in younger rats in a previous study (Giatti et al., 2015), suggesting significant interruption in brain dopaminergic activity occurs when AR activation is inhibited during the time testosterone levels are at their natural peak (Li et al., 2017).
This spatiotemporal observation of age-related difference is of potential relevance to the prevalence of PFS in young adult men of fertile age.
— Post-Finasteride Syndrome as an Epigenetic Post-Androgen Deprivation Syndrome: A potential pathological link between Drug-Induced Androgen Receptor Overexpression and Polyglutamine Toxicity, 2019
