Finasteride induced depression: a prospective study
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Finasteride is a competitive inhibitor of 5 alpha-reductase enzyme, and is used for treatment of benign prostatic hyperplasia and androgenetic alopecia. Animal studies have shown that finasteride might induce behavioral changes. Additionally, some cases of finasteride-induced depression have been reported in humans. The purpose of this study was to examine whether depressive symptoms or anxiety might be induced by finasteride administration.
One hundred and twenty eight men with androgenetic alopecia, who were prescribed finasteride (1 mg/day) were enrolled in this study. Information on depressed mood and anxiety was obtained by Beck Depression Inventory (BDI), and Hospital Anxiety and Depression Scale (HADS). Participants completed BDI and HADS questionnaires before beginning the treatment and also two months after it.
Mean age of the subjects was 25.8(± 4.4) years. At baseline, mean BDI and HADS depression scores were 12.11(± 7.50) and 4.04(± 2.51), respectively. Finasteride treatment increased both BDI (p < 0.001) and HADS depression scores significantly (p = 0.005). HADS anxiety scores were increased, but the difference was not significant (p = 0.061).
This preliminary study suggests that finasteride might induce depressive symptoms; therefore this medication should be prescribed cautiously for patients with high risk of depression. It seems that further studies would be necessary to determine behavioral effects of this medication in higher doses and in more susceptible patients.
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“Animal studies suggested that finasteride could alter 5alpha-reductase activity in some regions of the brain, and lead to behavioral and mood changes. It has been shown that finasteride is able to inhibit 5alpha-reductase in medial basal hypothalamus in pregnant rats, and induce behavioral changes . Significant inhibition of hypothalamic and pituitary 5alpha-reductase is also noticed in adult male rats . In addition to animal studies, although there are some case reports suggesting finasteride induction of depressive symptoms and anxiety in humans,  but no prospective study has been carried out, in order to investigate finasteride behavioral effects. In the present study, we have investigated any depressive symptoms or anxiety induced by finasteride administration, in the patients with diagnosis of androgenetic alopecia.”
5alpha-reductase is a critical enzyme in the conversion of several steroids such as testosterone, progesterone, aldosterone and corticosterone in the brain. This enzyme converts testosterone to the most natural potent androgen DHT, and also it acts an important role in conversion of progesterone to dihhydroprogesterone (DHP). DHP is further converted to allopregnanolone (5alpha, 3alpha-tetrahydroprogesterone) by 3alpha-HSD [9,21]. Allopregnanolone is a modulator of gamma amino butyric acid type A receptor (GABA-A), and increases chloride conductance. This neurosteroid has been found to exert anti-convulsant, anesthetic and anxiolytic effects [22-24]. Moreover, change in the levels of allopregnanolone is found to be associated with depressive disorders. [25,26]
Our results are in agreement with the past published reports , and indicate that finasteride might induce depressive symptoms. The 95% confidence interval, for the difference in the means of the BDI scores, was ranging from 0.34 to 1.04. This shows that the overall change induced by finasteride is minimal, but statistically significant. Anxiety scores were also increased, but the difference was not significant.
A decline in serum DHT level occurs after finasteride administration . This may contribute to finasteride induced depression. Some studies have been shown that serum DHT level, which is in equilibrium with the brain , is inversely associated with depression. A study by Barrett-Connor E. et al. showed that BDI scores were inversely associated with bioavailable testosterone and DHT level . Furthermore, it was found that DHT had anti-depressant effects on behavior of male rats and its replacement in castrated rats was able to partially decrease the immobility behavior, which is indicative of depression .
Finasteride induced psychiatric dysfunction can also be attributed to its inhibitory effect on androgen and steroid 5alpha-reduction in the brain. Animal studies suggest that finasteride has inhibitory effects on 5alpha-reduction of testosterone and progesterone in the brain and inhibits the formation of allopregnanolone [31,32]. Allopregnanolone has an important role in depressive disorders . In 1998 Romeo E. et al, revealed that episodes of unipolar major depressive disorder in men is associated with a decline in the plasma concentrations of allopregnanolone . Furthermore, a study carried out by Uzunova V. et al. showed that CSF levels of allopregnanolone were significantly lower in depressed patients, and there was negative correlation between allopregnanolone levels in CSF and HAM-D scores. .
Since finasteride is a potent 5AR type2 inhibitor and the predominant isoform of the enzyme in human brain is 5AR type1 [34,35], some points should be noted concerning finasteride inhibitory effect on brain steroid metabolism. (i) Although finasteride is a potent 5AR type2 inhibitor, but it has also some inhibitory effects on 5AR type1 . (ii) Finasteride administration in humans has been reported to be associated with some behavioral and mental disorders related to low levels of allopregnanolone in the brain . This may also improve the concept of brain allopregnanolone suppression by finasteride in humans.