Dutasteride and Mood

Most publications about the psychiatric side effects of 5-alpha-reductase inhibitors are devoted to finasteride. Dutasteride blocks the enzyme even more deeply, and it is logical to ask whether this intensifies the effect on mood. The editorial team gathered what is known about the neurobiology, epidemiology, and regulatory position specifically regarding dutasteride.

Neurobiology: why the question arises

The brain synthesizes its own steroid molecules — neurosteroids, which affect the excitability of neurons. An important role in their formation is played by 5-alpha-reductase, primarily type 1, which is expressed more noticeably in the brain of an adult than type 2. It is through this type that progesterone is converted to dihydroprogesterone and further to allopregnanolone.

Allopregnanolone enhances the action of GABA on GABA-A receptors and thereby calms the nervous system. A decrease in its level is associated with anxiety, depression, and disturbances in the response to stress. A similar pathway is followed by deoxycorticosterone with the formation of another neuroactive metabolite.

Finasteride inhibits type 1 weakly, dutasteride — potently. Therefore, theoretically, dutasteride is capable of affecting neurosteroid synthesis more strongly. At the same time, the question of how much the drug penetrates the blood-brain barrier and what concentrations are reached in the human brain has been insufficiently studied.

Thus, the biological hypothesis about an effect on mood is even stronger for dutasteride than for finasteride. However, as we will see further, clinical data do not always coincide with theoretical expectations.

Data from population studies

The most significant source of data on dutasteride is the population study by Welk and colleagues (2017) in JAMA Internal Medicine. It included men aged 66 and older from the province of Ontario who started taking finasteride or dutasteride, and comparable men without these drugs.

The authors found no increase in suicide risk but recorded a higher risk of self-harm and depression in the first 18 months of therapy. For depression, the increased risk was observed throughout the entire period of observation. Analysis separately by drug showed similar tendencies for both.

Other observational studies gave ambiguous results: in some of them the association with depression was weak or disappeared after accounting for comorbidities. Men with prostatic hyperplasia often have nocturia, sleep disturbances, and deterioration in quality of life, which in itself increases the risk of depression.

Interestingly, despite the stronger pharmacological blockade, there are significantly fewer reports of psychiatric side effects of dutasteride. This is partly explained by the fact that it is used to treat predominantly elderly men, rather than young people with baldness, who report symptoms and seek information more actively.

The position of regulatory agencies

The FDA prescribing information for dutasteride does not contain such detailed warnings about depression as the finasteride information does. However, the EMA Pharmacovigilance Risk Assessment Committee (PRAC) analyzed both drugs in its 2025 review.

As a result of the review, suicidal thoughts were confirmed as an adverse reaction of oral finasteride preparations. For dutasteride the data proved insufficient to reach the same conclusion, but the agency recommended continuing monitoring. This is a typical situation where the absence of evidence is not evidence of the absence of risk.

In clinical practice, doctors extrapolate caution from finasteride to dutasteride, taking into account the shared mechanism of action. Patients should be informed about the possibility of mood changes and asked to report them.

Indirect pathways of influence on well-being

Mood can change not only through neurosteroids. Sexual side effects — decreased libido, erectile dysfunction, reduced ejaculate volume — in some men noticeably affect self-esteem and relationships, which indirectly affects the emotional state.

Metabolic changes described for dutasteride — decreased insulin sensitivity and fat accumulation in the liver — are also associated with a worsening of general well-being, although a direct link with depression is not proven here.

Finally, the very disease for which dutasteride is prescribed affects the psyche. Nighttime awakenings due to the urge to urinate chronically disrupt sleep, and poor sleep is one of the strongest risk factors for depression.

• Sexual side effects and their impact on self-esteem.
• Sleep disturbances due to lower urinary tract symptoms.
• Metabolic changes and general fatigue.
• Anxiety about prostate health and prognosis.

Recommendations for monitoring

Before prescribing dutasteride, the doctor should know about depressive episodes, anxiety disorders, and the use of psychotropic drugs in the past. This is not a contraindication but a reason for closer monitoring, especially in the first months of treatment.

Patients and their loved ones should pay attention to a persistent decline in mood, loss of interest in usual activities, irritability, sleep disturbances, and any thoughts of self-harm. Such changes must be reported to the doctor immediately.

Since dutasteride is eliminated over weeks, the effect of its discontinuation does not occur immediately. This must be taken into account when assessing whether the symptoms are related to the drug. The decision to discontinue or change therapy is made by the doctor, taking into account the severity of the urological symptoms.

In the case of pronounced depression or suicidal thoughts, the priority is safety: seeking emergency psychiatric help, regardless of whether the symptoms are related to the drug.

Editorial conclusions

Dutasteride theoretically affects neurosteroid synthesis more strongly than finasteride, owing to the blockade of 5-alpha-reductase type 1.

Clinical data are limited: a population study showed an increased risk of depression for both drugs, but the number of reports of psychiatric side effects of dutasteride specifically is smaller. Regulators continue monitoring.

The practical approach is awareness, attention to mood changes, and timely consultation with a doctor.

We also recommend reading "Finasteride and Mood," "Dutasteride and Libido," and "Dutasteride and the Liver."

References

1. Welk B, McArthur E, Ordon M, et al. Association of suicidality and depression with 5α-reductase inhibitors. JAMA Intern Med. 2017;177(5):683–691.
2. Finn DA, Beadles-Bohling AS, Beckley EH, et al. A new look at the 5alpha-reductase inhibitor finasteride. CNS Drug Rev. 2006;12(1):53–76.
3. Traish AM. Post-finasteride syndrome: a surmountable challenge for clinicians. Fertil Steril. 2020;113(1):21–50.
4. Nguyen DD, Marchese M, Cone EB, et al. Investigation of suicidality and psychological adverse events in patients treated with finasteride. JAMA Dermatol. 2021;157(1):35–42.
5. Clark RV, Hermann DJ, Cunningham GR, et al. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5α-reductase inhibitor. J Clin Endocrinol Metab. 2004;89(5):2179–2184.
6. European Medicines Agency. PRAC review of finasteride- and dutasteride-containing medicines: suicidal ideation. Amsterdam: EMA; 2025.
7. GlaxoSmithKline. Avodart (dutasteride) soft gelatin capsules: prescribing information. U.S. Food and Drug Administration.