Brain, mind & behavior

• Behavior & stress response
• Cognition, memory & speech
• Depression & suicidality

Behavior & stress response

Animal studies

Bartolomé I, Llidó A, Darbra S, Pallarès M. Early postnatal allopregnanolone levels alteration and adult behavioral disruption in rats: Implication for drug abuse. Neurobiol Stress. 2019;12:100208. Published 2019 Dec 27. doi:10.1016/j.ynstr.2019.100208 | PubMed

Dhillon HK, Singh T, Goel RK. Ferulic acid inhibits catamenial epilepsy through modulation of female hormones. Metab Brain Dis. 2022 Aug 6. doi:10.1007/s11011-022-01054-w • PubMed [Finasteride increased seizure susceptibility and depression-like characteristics]

Diviccaro S, Giatti S, Borgo F, et al. Treatment of male rats with finasteride, an inhibitor of 5alpha-reductase enzyme, induces long-lasting effects on depressive-like behavior, hippocampal neurogenesis, neuroinflammation and gut microbiota composition. Psychoneuroendocrinology. 2019;99:206-215. doi:10.1016/j.psyneuen.2018.09.021 | PubMed

Frau R, Pillolla G, Bini V, Tambaro S, Devoto P, Bortolato M. Inhibition of 5α-reductase attenuates behavioral effects of D1-, but not D2-like receptor agonists in C57BL/6 mice. Psychoneuroendocrinology. 2013 Apr;38(4):542-51. doi:10.1016/j.psyneuen.2012.07.014 | PubMed

Godar SC, Cadeddu R, Floris G, et al. The steroidogenesis inhibitor finasteride reduces the response to both stressful and rewarding stimuli. Biomolecules. 2019;9(11):749. doi:10.3390/biom9110749 | PubMed

Li L, Kang YX, Ji XM, et al. Finasteride inhibited brain dopaminergic system and open-field behaviors in adolescent male rats. CNS Neurosci Ther. 2018;24(2):115-125. doi:10.1111/cns.12781

Mann PE. Finasteride delays the onset of maternal behavior in primigravid rats. Physiol Behav. 2006;88(4-5):333-338. doi:10.1016/j.physbeh.2006.04.008 | PubMed

Maurice-Gélinas C, Deslauriers J, Monpays C, Sarret P, Grignon S. The 5α-reductase inhibitor finasteride increases suicide-related aggressive behaviors and blocks clozapine-induced beneficial effects in an animal model of schizophrenia. Physiol Behav. 2018;191:65–72. doi:10.1016/j.physbeh.2018.03.036 | PubMed

Soggiu A, Piras C, Greco V, et al. Exploring the neural mechanisms of finasteride: a proteomic analysis in the nucleus accumbens. Psychoneuroendocrinology. 2016;74:387–396. doi:10.1016/j.psyneuen.2016.10.001 | PubMed

Cognition & memory

[Preprint] Fusaroli M, Simonsen A, Borrie SA, et al. Identifying medications underlying communication atypicalities in psychotic and affective disorders: a pharmacovigilance study within the FDA Adverse Event Reporting System. medRxiv. Published online 2022. doi:10.1101/2022.09.05.22279609

This preprint found an elevated risk of ‘low productivity speech or thought’ linked to finasteride, in a non-neuropsychiatric population (see Supplement 2).

Ganzer CA, Jacobs AR, Iqbal F. Persistent sexual, emotional, and cognitive impairment post-finasteride: a survey of men reporting symptoms. Am J Mens Health. 2015;9(3):222-228. doi:10.1177/1557988314538445 | PubMed

Garcia-Argibay M, Hiyoshi A, Fall K, Montgomery S. Association of 5α-reductase inhibitors with dementia, depression, and suicide. JAMA Netw Open. 2022. doi:10.1001/jamanetworkopen.2022.48135 • PubMed

Kim YJ, Tae BS, Bae JH. Cognitive function and urologic medications for lower urinary tract symptoms. Int Neurourol J. 2020 Sep;24(3):231-240. doi:10.5213/inj.2040082.041 | PubMed

Welk B, McArthur E, Ordon M, Morrow SA, Hayward J, Dixon S. The risk of dementia with the use of 5 alpha reductase inhibitors. J Neurol Sci. 2017;379:109-111. doi:10.1016/j.jns.2017.05.064 | PubMed

Animal studies

Ahire A, Nair, KP, Shankaranarayana Rao BS, Srikumar BN. The potential involvement of cholinergic system in finasteride induced cognitive dysfunction. Psychoneuroendocrinology. 2021 Feb;124:105066. doi:10.1016/j.psyneuen.2020.105066 | PubMed

Diviccaro S, Giatti S, Borgo F, et al. Treatment of male rats with finasteride, an inhibitor of 5alpha-reductase enzyme, induces long-lasting effects on depressive-like behavior, hippocampal neurogenesis, neuroinflammation and gut microbiota composition. Psychoneuroendocrinology. 2019. doi:10.1016/j.psyneuen.2018.09.021 • PubMed

Mendell AL, Creighton SD, Wilson HA, et al. Inhibition of 5α reductase impairs cognitive performance, alters dendritic morphology and increases Tau phosphorylation in the hippocampus of male 3xTg-AD mice. Neuroscience. 2020 Mar 1;429:185-202. doi:10.1016/j.neuroscience.2020.01.011 | PubMed

Römer B, Pfeiffer N, Lewicka S, et al. Finasteride treatment inhibits adult hippocampal neurogenesis in male mice. Pharmacopsychiatry. 2010;43(5):174-178. doi:10.1055/s-0030-1249095 | PubMed

Depression and suicidality

Ali AK, Heran BS, Etminan M. Persistent sexual dysfunction and suicidal ideation in young men treated with low-dose finasteride: a pharmacovigilance study. Pharmacotherapy. 2015;35(7):687-695. doi:10.1002/phar.1612 | PubMed

Altomare G, Capella GL. Depression circumstantially related to the administration of finasteride for androgenetic alopecia. J Dermatol. 2002;29(10):665–669. doi:10.1111/j.1346-8138.2002.tb00200.x | PubMed

Baldessarini RJ, Pompili M. Further studies of effects of finasteride on mood and suicidal risk. J Clin Psychopharmacol. 2021 Nov-Dec 01. doi:10.1097/jcp.0000000000001485 | PubMed

Bortnick EM, Simma-Chiang V, Kaplan SA. Long-term consequences of medical therapy for benign prostatic hyperplasia. Rev Urol. 2019;21(4):154-157. PubMed • PMC full text

Campbell K, Velazquez O, Sullivan J, Lipshultz L. Finasteride-associated suicide and depression in men treated for hypogonadism and impotence. The Journal of Sexual Medicine. 2022;19(4):S4-S5. doi:10.1016/j.jsxm.2022.01.019

Deng T, Duan X, He Z, Zhao Z, Zeng G. Association between 5-alpha reductase inhibitor use and the risk of depression: a meta-analysis. Urol J. 2020;10.22037/uj.v16i7.5866. doi:10.22037/uj.v16i7.5866 | PubMed

Dusková M, Hill M, Hanus M, Matousková M, Stárka L. Finasteride treatment and neuroactive steroid formation. Prague Med Rep. 2009;110(3):222-230. Journal site | PubMed

Dyson TE, Cantrell MA, Lund BC. Lack of association between 5α-reductase inhibitors and depression. J Urol. 2020;101097JU0000000000001079. doi:10.1097/JU.0000000000001079 | PubMed

Garcia-Argibay M, Hiyoshi A, Fall K, Montgomery S. Association of 5α-reductase inhibitors with dementia, depression, and suicide. JAMA Netw Open. 2022. doi:10.1001/jamanetworkopen.2022.48135 • PubMed

Gur S, Kadowitz PJ, Hellstrom WJ. Effects of 5-alpha reductase inhibitors on erectile function, sexual desire and ejaculation. Expert Opin Drug Saf. 2013;12(1):81-90. doi:10.1517/14740338.2013.742885

Hagberg KW, Divan HA, Nickel JC, Jick SS. Risk of incident antidepressant-treated depression associated with use of 5α-reductase inhibitors compared with use of α-blockers in men with benign prostatic hyperplasia: a population-based study using the Clinical Practice Research Datalink. Pharmacotherapy. 2017;37(5):517‐527. doi:10.1002/phar.1925 | PubMed

Irwig MS. Depressive symptoms and suicidal thoughts among former users of finasteride with persistent sexual side effects. J Clin Psychiatry. 2012;73(9):1220-1223. doi:10.4088/JCP.12m07887

Irwig MS. Finasteride and suicide: a postmarketing case series. Dermatology. 2020:1-6. doi:10.1159/000505151 | PubMed

Kim JA, Choi D, Choi S, Chang J, Park SM. The association of 5α-reductase inhibitor with suicidality. Psychosom Med. 2020 Apr;82(3):331-336. doi:10.1097/PSY.0000000000000784 | PubMed

Kim JH, Shim SR, Khandwala Y, Del Giudice F, Sorensen S, Chung BI. Risk of depression after 5 alpha reductase inhibitor medication: meta-analysis. World J Mens Health. 2020 Oct;38(4):535-544. doi:10.5534/wjmh.190046 | PubMed

Melcangi RC, Caruso D, Abbiati F, et al. Neuroactive steroid levels are modified in cerebrospinal fluid and plasma of post-finasteride patients showing persistent sexual side effects and anxious/depressive symptomatology. J Sex Med. 2013;10(10):2598-2603. doi:10.1111/jsm.12269 | PubMed

Muderrisoglu AE, Becher KF, Madersbacher S, Michel MC. Cognitive and mood side effects of lower urinary tract medication. Expert Opin Drug Saf. 2019 Oct;18(10):915-923. doi:10.1080/14740338.2019.1652269 | PubMed

Nguyen DD, Marchese M, Cone EB, et al. Investigation of suicidality and psychological adverse events in patients treated with finasteride. JAMA Dermatol. 2020 Nov 11. doi:10.1001/jamadermatol.2020.3385 | PubMed

Pompili M, Magistri C, Maddalena S, Mellini C, Persechino S, Baldessarini RJ. Risk of depression associated with finasteride treatment. J Clin Psychopharmacol. 2021 Mar 31. doi:10.1097/JCP.0000000000001379 | PubMed

Rahimi-Ardabili B, Pourandarjani R, Habibollahi P, Mualeki A. Finasteride induced depression: a prospective study. BMC Clin Pharmacol. 2006;6:7. doi:10.1186/1472-6904-6-7 | PubMed

Römer B, Gass P. Finasteride-induced depression: new insights into possible pathomechanisms [published correction appears in J Cosmet Dermatol. 2011 Mar;10(1):85]. J Cosmet Dermatol. 2010;9(4):331-332. doi:10.1111/j.1473-2165.2010.00533.x | PubMed

Saengmearnuparp T, Lojanapiwat B, Chattipakorn N, Chattipakorn S. The connection of 5-alpha reductase inhibitors to the development of depression. Biomed Pharmacother. 2021 Aug 31;143:112100. doi:10.1016/j.biopha.2021.112100 | PubMed | Full text

Schmutz JL. Dépression et idées suicidaires avec le finastéride [Depression and suicidal thoughts associated with finasteride]. Ann Dermatol Venereol. 2018;145(2):155–156. doi:10.1016/j.annder.2018.01.006 | PubMed

Singh MK, Avram M. Persistent sexual dysfunction and depression in finasteride users for male pattern hair loss: a serious concern or red herring? J Clin Aesthet Dermatol. 2014;7(12):51-55. PubMed

Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML. Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients. J Sex Med. 2011;8(3):872-884. doi:10.1111/j.1743-6109.2010.02157.x | PubMed

Traish AM, Mulgaonkar A, Giordano N. The dark side of 5α-reductase inhibitors’ therapy: sexual dysfunction, high Gleason grade prostate cancer and depression. Korean J Urol. 2014;55(6):367-379. doi:10.4111/kju.2014.55.6.367 | PubMed

Welk B, McArthur E, Ordon M, Anderson KK, Hayward J, Dixon S. Association of suicidality and depression with 5α-reductase inhibitors. JAMA Intern Med. 2017;177(5):683–691. doi:10.1001/jamainternmed.2017.0089 | PubMed

Animal studies

Diviccaro S, Giatti S, Borgo F, et al. Treatment of male rats with finasteride, an inhibitor of 5alpha-reductase enzyme, induces long-lasting effects on depressive-like behavior, hippocampal neurogenesis, neuroinflammation and gut microbiota composition. Psychoneuroendocrinology. 2019;99:206-215. doi:10.1016/j.psyneuen.2018.09.021| PubMed

Maurice-Gélinas C, Deslauriers J, Monpays C, Sarret P, Grignon S. The 5α-reductase inhibitor finasteride increases suicide-related aggressive behaviors and blocks clozapine-induced beneficial effects in an animal model of schizophrenia. Physiol Behav. 2018;191:65–72. doi:10.1016/j.physbeh.2018.03.036 | PubMed

Sasibhushana RB, Shankaranarayana Rao BS, Srikumar BN. Repeated finasteride administration induces depression-like behavior in adult male rats. Behav Brain Res. 2019;365:185–189. doi:10.1016/j.bbr.2019.03.006 | PubMed