madman
Super Moderator
Investigation of Suicidality and Psychological Adverse Events in Patients Treated With Finasteride
IMPORTANCE There is ongoing controversy about the adverse events of finasteride, a drug used in the management of alopecia and benign prostatic hyperplasia (BPH). In 2012, reports started emerging on men who had used finasteride and either attempted or completed suicide.
OBJECTIVE To investigate the association of suicidality (ideation, attempt, and completed suicide) and psychological adverse events (depression and anxiety) with finasteride use.
DESIGN, SETTING, AND PARTICIPANTS This pharmacovigilance case-noncase study used disproportionality analysis (case-noncase design) to detect signals of adverse reaction of interest reported with finasteride in VigiBase, the World Health Organization’s global database of individual case safety reports. To explore the strength of association, the reporting odds ratio (ROR), a surrogate measure of association used in disproportionality the analysis was used. Extensive sensitivity analyses included stratifying by indication (BPH and alopecia) and age (45 and >45 years); comparing finasteride signals with those of drugs with different mechanisms but used for similar indications (minoxidil for alopecia and tamsulosin hydrochloride for BPH); comparing finasteride with a drug with a similar mechanism of action and adverse event profile (dutasteride), and comparing reports of suicidality before and after 2012. Data were obtained in June 2019 and analyzed from January 25 to February 28, 2020.
EXPOSURES Reported finasteride use.
MAIN OUTCOMES AND MEASURES Suicidality and psychological adverse events.
RESULTS VigiBase contained 356 reports of suicidality and 2926 reports of psychological adverse events (total of 3282 adverse events of interest) in finasteride users (3206 male [98.9%]; 615 of 868 [70.9%] with data available aged 18-44 years). A significant disproportionality signal for suicidality (ROR, 1.63; 95% CI, 1.47-1.81) and psychological adverse events (ROR, 4.33; 95% CI, 4.17-4.49) in finasteride was identified. In sensitivity analyses, younger patients (ROR, 3.47; 95% CI, 2.90-4.15) and those with alopecia (ROR, 2.06; 95% CI, 1.81-2.34) had significant disproportionality signals for increased suicidality; such signals were not detected in older patients with BPH. Sensitivity analyses also showed that the reports of these adverse events significantly increased after 2012 (ROR, 2.13; 95% CI, 1.91-2.39).
CONCLUSIONS AND RELEVANCE In this pharmacovigilance case-noncase study, significant RORs of suicidality and psychological adverse events were associated with finasteride use in patients younger than 45 years who used finasteride for alopecia. The sensitivity analyses suggest that these disproportional signals of adverse events may be due to stimulated reporting and/or younger patients being more vulnerable to finasteride’s adverse effects.
Concerns have emerged about the adverse effects of finasteride, a drug indicated for the management of both male-pattern baldness (androgenetic alopecia)1,2 and benign prostatic hyperplasia (BPH).3-5 Reports of suicidality and psychological adverse events related to finasteride have led to the coining of the term post finasteride syndrome and the creation of organizations such as the Post-Finasteride Syndrome Foundation.6-10 In 2011, a postmarketing report was sent to the US Food and Drug Administration suggests that finasteride may be linked to depression, self-harm, and suicide.11 In the last 5 years, health authorities in Canada, Korea, New Zealand and the United Kingdom have also acknowledged these potential adverse effects and issued warnings for finasteride.12-15
There is a plausible biological basis linking finasteride, a 5α-reductase inhibitor (5ARI), with depression and anxiety. Some reports suggest that men with depression have lower levels of the neurosteroid allopregnanolone, which is produced by the 5α-reductase enzyme and has antidepressant and anxiolytic effects.16-18 Broader clinical context, however, is lacking for this association. At the population level, studies have found an increased risk of depression associated with finasteride use among patients with BPH.19-21 Most of these studies relied on claims data,22 although 1 study that used a validated screening tool for depression23 found an association between finasteride exposure and depression.
Studies on the association between suicidality and finasteride use are limited. In a large cohort of men 66 years or older with BPH, Welk et al19 found no increased risk of completed suicide with finasteride but did identify an increased risk of self-harm compared with unexposed men. On the contrary, an analysis of the US Food and Drug Administration’s Adverse Event Reporting System database found disproportional reporting of suicidal ideation among men using finasteride for alopecia, but the sample size was limited to 39 men.24 Given the limited evidence, we performed a pharmacovigilance study to further investigate the association between finasteride use and suicidality (ideation, attempt, and completed suicide) and psychological adverse events (depression and/or anxiety) using VigiBase, the World Health Organization’s international database of individual case safety reports.25
*This is the first analysis, to our knowledge, of suicidality and psychological adverse events in association with finasteride in VigiBase, an international pharmacovigilance database, with comprehensive sensitivity analyses examining pharmacodynamically different drugs prescribed for similar indications (minoxidil and tamsulosin) as well as a drug with similar mechanisms of action (dutasteride). In the context of increased scrutiny of post finasteride syndrome, our exploratory findings highlight the need to further investigate the adverse events of finasteride use among young patients treated with the drug for alopecia, the cohort driving the disproportionality signal. Clinicians should pay greater attention to the psychological adverse effects of finasteride when prescribing them, especially in the younger population using the drug for hair loss. In addition, our sensitivity analyses shed light on potential biases that may confound the association between finasteride use and suicidality, namely, stimulated reporting, which should be further investigated.
Conclusions
Using validated pharmacovigilance methods, 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. In sensitivity analyses, drugs with similar indications but different mechanisms of action and drugs with similar mechanisms of action and adverse effect profiles did not have disproportional reporting of suicidality nor psychological adverse events. Disproportional reporting of suicidality associated with finasteride use was observed after 2012. In light of these exploratory findings, disproportional signals associated with finasteride may be attributed to reporting biases, namely, stimulated reporting, or to greater repercussions of adverse effects and/or inherent psychological morbidities among younger men. Suicidality and psychological adverse events associated with finasteride use by young patients undergoing treatment for alopecia and potential biases confounding this association merit further investigation.
IMPORTANCE There is ongoing controversy about the adverse events of finasteride, a drug used in the management of alopecia and benign prostatic hyperplasia (BPH). In 2012, reports started emerging on men who had used finasteride and either attempted or completed suicide.
OBJECTIVE To investigate the association of suicidality (ideation, attempt, and completed suicide) and psychological adverse events (depression and anxiety) with finasteride use.
DESIGN, SETTING, AND PARTICIPANTS This pharmacovigilance case-noncase study used disproportionality analysis (case-noncase design) to detect signals of adverse reaction of interest reported with finasteride in VigiBase, the World Health Organization’s global database of individual case safety reports. To explore the strength of association, the reporting odds ratio (ROR), a surrogate measure of association used in disproportionality the analysis was used. Extensive sensitivity analyses included stratifying by indication (BPH and alopecia) and age (45 and >45 years); comparing finasteride signals with those of drugs with different mechanisms but used for similar indications (minoxidil for alopecia and tamsulosin hydrochloride for BPH); comparing finasteride with a drug with a similar mechanism of action and adverse event profile (dutasteride), and comparing reports of suicidality before and after 2012. Data were obtained in June 2019 and analyzed from January 25 to February 28, 2020.
EXPOSURES Reported finasteride use.
MAIN OUTCOMES AND MEASURES Suicidality and psychological adverse events.
RESULTS VigiBase contained 356 reports of suicidality and 2926 reports of psychological adverse events (total of 3282 adverse events of interest) in finasteride users (3206 male [98.9%]; 615 of 868 [70.9%] with data available aged 18-44 years). A significant disproportionality signal for suicidality (ROR, 1.63; 95% CI, 1.47-1.81) and psychological adverse events (ROR, 4.33; 95% CI, 4.17-4.49) in finasteride was identified. In sensitivity analyses, younger patients (ROR, 3.47; 95% CI, 2.90-4.15) and those with alopecia (ROR, 2.06; 95% CI, 1.81-2.34) had significant disproportionality signals for increased suicidality; such signals were not detected in older patients with BPH. Sensitivity analyses also showed that the reports of these adverse events significantly increased after 2012 (ROR, 2.13; 95% CI, 1.91-2.39).
CONCLUSIONS AND RELEVANCE In this pharmacovigilance case-noncase study, significant RORs of suicidality and psychological adverse events were associated with finasteride use in patients younger than 45 years who used finasteride for alopecia. The sensitivity analyses suggest that these disproportional signals of adverse events may be due to stimulated reporting and/or younger patients being more vulnerable to finasteride’s adverse effects.
Concerns have emerged about the adverse effects of finasteride, a drug indicated for the management of both male-pattern baldness (androgenetic alopecia)1,2 and benign prostatic hyperplasia (BPH).3-5 Reports of suicidality and psychological adverse events related to finasteride have led to the coining of the term post finasteride syndrome and the creation of organizations such as the Post-Finasteride Syndrome Foundation.6-10 In 2011, a postmarketing report was sent to the US Food and Drug Administration suggests that finasteride may be linked to depression, self-harm, and suicide.11 In the last 5 years, health authorities in Canada, Korea, New Zealand and the United Kingdom have also acknowledged these potential adverse effects and issued warnings for finasteride.12-15
There is a plausible biological basis linking finasteride, a 5α-reductase inhibitor (5ARI), with depression and anxiety. Some reports suggest that men with depression have lower levels of the neurosteroid allopregnanolone, which is produced by the 5α-reductase enzyme and has antidepressant and anxiolytic effects.16-18 Broader clinical context, however, is lacking for this association. At the population level, studies have found an increased risk of depression associated with finasteride use among patients with BPH.19-21 Most of these studies relied on claims data,22 although 1 study that used a validated screening tool for depression23 found an association between finasteride exposure and depression.
Studies on the association between suicidality and finasteride use are limited. In a large cohort of men 66 years or older with BPH, Welk et al19 found no increased risk of completed suicide with finasteride but did identify an increased risk of self-harm compared with unexposed men. On the contrary, an analysis of the US Food and Drug Administration’s Adverse Event Reporting System database found disproportional reporting of suicidal ideation among men using finasteride for alopecia, but the sample size was limited to 39 men.24 Given the limited evidence, we performed a pharmacovigilance study to further investigate the association between finasteride use and suicidality (ideation, attempt, and completed suicide) and psychological adverse events (depression and/or anxiety) using VigiBase, the World Health Organization’s international database of individual case safety reports.25
*This is the first analysis, to our knowledge, of suicidality and psychological adverse events in association with finasteride in VigiBase, an international pharmacovigilance database, with comprehensive sensitivity analyses examining pharmacodynamically different drugs prescribed for similar indications (minoxidil and tamsulosin) as well as a drug with similar mechanisms of action (dutasteride). In the context of increased scrutiny of post finasteride syndrome, our exploratory findings highlight the need to further investigate the adverse events of finasteride use among young patients treated with the drug for alopecia, the cohort driving the disproportionality signal. Clinicians should pay greater attention to the psychological adverse effects of finasteride when prescribing them, especially in the younger population using the drug for hair loss. In addition, our sensitivity analyses shed light on potential biases that may confound the association between finasteride use and suicidality, namely, stimulated reporting, which should be further investigated.
Conclusions
Using validated pharmacovigilance methods, 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. In sensitivity analyses, drugs with similar indications but different mechanisms of action and drugs with similar mechanisms of action and adverse effect profiles did not have disproportional reporting of suicidality nor psychological adverse events. Disproportional reporting of suicidality associated with finasteride use was observed after 2012. In light of these exploratory findings, disproportional signals associated with finasteride may be attributed to reporting biases, namely, stimulated reporting, or to greater repercussions of adverse effects and/or inherent psychological morbidities among younger men. Suicidality and psychological adverse events associated with finasteride use by young patients undergoing treatment for alopecia and potential biases confounding this association merit further investigation.
