Depression related to the administration of Finasteride

Depression circumstantially related to the administration of finasteride for androgenetic alopecia. … s=12433001


In this paper we report 19 patients (14 males, 5 females; mean age 28.16 years +/- 7.68 SD) out of a series of 23 (17 males, 5 females) who developed a mood disturbance (moderate to severe depression) during treatment with finasteride, 1 mg/day orally, for androgenetic alopecia (Hamilton subtypes III-V; Ludwig subtypes I-II).

Depression, which significatively impaired sociofamilial relations, sleep and eating behaviour, was associated to marked anxiety in some cases, developed after 9-19 weeks of treatment with finasteride, and promptly resolved after suspension of the drug.

Two patients accepted reintroduction of the drug, and depression relapsed within 2 weeks.

Depression as an adverse effect of finasteride has been reported only once.

Further studies are needed to confirm our circumstantial observations, which are based on a retrospective series of patients.

PMID: 12433001 [PubMed - indexed for MEDLINE]

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.

FULL TEXT: … id=1622749

Selected bits:

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 [13]. Significant inhibition of hypothalamic and pituitary 5alpha-reductase is also noticed in adult male rats [14]. In addition to animal studies, although there are some case reports suggesting finasteride induction of depressive symptoms and anxiety in humans, [15] 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 [15], 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 [27]. This may contribute to finasteride induced depression. Some studies have been shown that serum DHT level, which is in equilibrium with the brain [28], 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 [29]. 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 [30].

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 [26]. 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 [25]. 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. [33].

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 [36]. (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 [37]. This may also improve the concept of brain allopregnanolone suppression by finasteride in humans.

Finasteride: suspected association with depression

PAGE 3, Canadian Adverse Reaction Report:

A white man in his mid-40s with no prior history of psychiatric problems was treated with finasteride for male-pattern hair loss. Clinical depression developed about 3 months after the onset of therapy.

The depression was described as moderately severe but was unresponsive to treatment with various antidepressants. Treatment was maintained for 4 years. Following cessation of the finasteride therapy, the depression resolved in about 2 weeks, and the patient made a complete recovery.

A published report has described 19 cases (14 males, 5 females) in whom moderate to severe depression developed during treatment with finasteride (1 mg/d orally) for androgenetic alopecia.1

Influence of the 5 α-reductase inhibitor type 2 on circulating neuroactive steroids … 16p626.htm

The 5α-reductase is one of the enzyme of steroid synthesis and founded in two isoformes. Two distinct 5α-reductase isoenzymes, type I and type II, are found across mammalian species.

Each of these isoenzymes is differentially expressed in tissues and during distinct developmental stages and also in different species.

The 5α-reductase is enzyme responsible for the reduction of testosterone to dihydrostestosterone, progesterone to dihydroprogesterone and deoxycorticosterone to dihydrodeoxycorticosterone.

These steroids and their metabolites (termed neuroactvive steroids) have rapid non-genomic effects on brain function and behavior, primarily via an enhancement of γ-aminobutyric acid (GABA)ergic inhibitory neurotransmission. Neuroactive steroids have through GABA receptor anticonvulsant, antidepressant and anxiolytic effects.

Finasteride is the first 5α-reductase type II inhibitor that was introduced to clinical practice in 1992 for the treatment of benign prostatic hyperplasia in the dose of 5 mg/day and few years later for androgentic alopecia in dose of 1 mg/day. There are some reports suggesting finasteride induction of depressive symptoms and anxiety in human.

The steroid profile of patients treated by finasteride was detected only in analyse of urine (it was strikingly similar to that of male pseudohermaphrodites with inherited 5 alpha-reductase deficiency).

In our study a group of 32 men (12 men with androgenetic alopecia and 20 men wih bening prostatic hyperplasia) was examined. In all individual, their hormonal profile of steroids hormones in blood was determined.

Finasteride in the daily dose of 1 mg (men with androgenetic alopecia) or 5 mg (men with benign prostatic hyperplasia) was administrated for 4 months.

After the treatment the same hormonal profile was determined. In addition to the decrese of dihydrotestosterone level after treatement, the alteration in other 5 alfa steroids metabolites was found, which could explain the depresive symptomatology.

The study was supported by grant No.NR/8525 – 5 of the IGA MZCR.

Hmmm, this definitely suggests that the brain chemistry is being altered.

Emerging Roles for Neurosteroids in Sexual Behavior and Function … l/29/5/524

"Notably, preliminary studies indicate that, as in the rodent, finasteride may increase depression in men as a result of the loss of allopregnanolone (eg, Altomare et al, 2002; Rahimi-Ardabili et al, 2006).

This raises the possibility that lowered levels of the neurosteroid contribute to the reduced sexual desire reported for some patients.

Treatment strategies that take into account effects on neurosteroids and the development of drugs that singularly target neurosteroid biosynthesis may therefore provide superior therapies for patients. "

Treatment options:

"… An alternative approach is to use drugs that specifically increase neurosteroid concentrations. The antipsychotic agents clozapine and olanzapine may improve schizophrenia by increasing brain allopregnanolone synthesis (Marx et al, 2006).

Similarly, the reduction in aggression induced by fluoxetine may be directly caused by increased allopregnanolone levels in the CNS, because the drug is effective at levels 10-fold lower than those that block serotonin reuptake (Pinna et al, 2003). "

Finasteride treatment and neuroactive steroid formation … d_RVDocSum

Prague Med Rep. 2009;110(3):222-30

Dusková M, Hill M, Hanus M, Matousková M, Stárka L.
Institute of Endocrinology, Prague, Czech Republic.

Finasteride is the 5alpha-reductase inhibitor that received clinical approval for the treatment of human benign prostate hyperplasia and androgenetic alopecia.

The 5alpha-reductase is enzyme responsible for the reduction of testosterone to dihydrostestosterone, progesterone to dihydroprogesterone and deoxycorticosterone to dihydrodeoxycorticosterone, steroids modulating the action of gamma-aminobutyric acid on GABA receptors. These neuroactive steroids possess anticonvulsant, antidepressant and anxiolytic effects.

The objective of the study was to determine the effect of finasteride therapy on a broad steroid spectrum in men with benign prostate hyperplasia. A group of 20 men with benign prostate hyperplasia was involved in the present study. Finasteride in the daily dose of 5 mg/day was administrated for 4 months. In all individuals, their hormonal profile of steroid hormones was determined before and after 4 months lasting finasteride treatment.

Finasteride treatment resulted in a significant decrease all alpha-reduced and increase of most 5beta-reduced metabolites of testosterone and progesterone as well as in an increase of 7alpha-hydoxyderivatives, which are known as neuroactive steroids acting by modulation of GABAA and NMDA receptors in the brain.

In the course of finasteride treatment the decrease of the concentration of circulating steroids with known inhibitory activity on GABA-ergic excitation in the brain is very probably an important factors contributing to the development of the symptoms of depression seen in some isolated cases of finasteride administration.

The influence of low dose finasteride, a type II 5α-reductase inhibitor, on circulating neuroactive steroids … I.2010.010

Background: Finasteride is a 5α-reductase inhibitor that has received clinical approval for the treatment of human benign prostatic hyperplasia and androgenetic alopecia. The treatment is practically without side effects, although some occasional cases of depression syndrome have been reported. 5α-Reductase is an enzyme responsible for the reduction of testosterone, progesterone or deoxycorticosterone to their 5α-reduced derivatives possessing anticonvulsant, antidepressant, and anxiolytic activity. Therefore, the formation of GABAergic neuroactive steroids is likely to be impacted by finasteride.

Objective: The objective of the study was to show how the treatment of premature androgenetic alopecia with low doses (1 mg/day) of finasteride influences the broad spectrum of steroids with potential neuroactivity.

Methods: A group of 12 men with premature androgenetic alopecia participated in the present study. The steroid hormone profile was determined for all individuals. Finasteride was administered for 4 months at a daily dose of 1 mg. After the treatment, the same hormonal profile was determined again.

Results: 5α-Reduced steroids, e.g., 5α-dihydrotestosterone, androsterone, epiandrosterone, 5α-androstene-3α,17β-diol, allopregnanolone, isopregnaolone, and some 5-ene steroids, such as dehydroepiandrosterone and pregnenolone, decreased gradually during treatment.

Conclusions: The decrease of 5α-reduced steroids, especially of allopregnanediol, dihydrotestosterone, and pregnenolone, is probably one of the factors responsible for the increased occurrence of depression in men treated with finasteride, even at low doses.

Finasteride treatment inhibits adult hippocampal neurogenesis in male mice.
Pharmacopsychiatry. 2010 Jul;43(5):174-8. Epub 2010 May 18.

INTRODUCTION: The 5-alpha-reductase inhibitor finasteride is used for the treatment of androgenic alopecia, benign prostate hyperplasia and prostate cancer. Besides inhibiting the conversion of testosterone to the biologically more active 5alpha-dihydrotestosterone, it also inhibits the production of neurosteroids. Decreased neurosteroid levels are postulated to be involved in the pathophysiology of psychiatric disorders such as depression. As neurosteroids metabolized by 5-alpha-reductase influence neural plasticity, we investigated whether finasteride treatment alters adult hippocampal neurogenesis, implicated in the pathophysiology of depression.

METHODS: Male C57BL/6N mice were treated subchronically (7 days) with finasteride or vehicle. Adult neurogenesis was assessed at two different time points after treatment (day 1; day 35) using immunohistochemistry.

RESULTS: Finasteride treatment led to a significant decrease in brain 5alpha-dihydrotestosterone levels and induced a reversible reduction in the number of newborn cells and young neurons in the hippocampus. 35 days after the last finasteride injection, neurogenesis had returned to normal.

DISCUSSION: These data indicate that inhibition of 5-alpha-reductase activity by finasteride treatment influences neuronal plasticity on a structural level. These changes might contribute to the pathophysiology of depressive episodes observed after finasteride treatment.

Finasteride-induced depression: new insights into possible pathomechanisms

5-alpha-reductase is involved as a rate-imitating enzyme in the metabolism of steroids.

Several 5-alpha-reduced steroids such as dihydrotestosterone, allopregnanolone or tetrahydrocorticosterone have neurotrophic, neuroprotective, and anxiolytic properties. Reduced 5-alpha-reductase activity has been observed during depressive illness in humans.

Finasteride inhibits 5-alpha-reductase and can robustly induce anxious and depressive behaviors in rodents. In humans finasteride treatment has been linked to an increase of depressive symptoms.

A recent study reported that finasteride treatment inhibits hippocampal neurogenesis in mice. As hippocampal neurogenesis has been linked to emotional behavior, this could be of possible relevance for the pathophysiology of affective disorders.

Further studies are needed to evaluate potential neuropsychiatric side effects of finasteride treatment in humans.

It could also be a clear explanation of poor memory in finasteride victims, since that area of the brain is crucial for forming and recalling events. Nice to see updates in this kind of finasteride research.

December 2010 - Merck USA adds DEPRESSION as a reported post-marketing side effect:

Pg. 2 - What are the possible side effects of PROPECIA?

Pg. 10 - Postmarketing Experience for PROPECIA (finasteride 1 mg)