The connection of 5-alpha reductase inhibitors to the development of depression

Thiraphat Saengmearnuparp; Bannakij Lojanapiwat; Nipon Chattipakorn; Siriporn Chattipakorn

doi:10.1016/j.biopha.2021.112100

The connection of 5-alpha reductase inhibitors to the development of depression

Biomed Pharmacother. 2021 Nov:143:112100. doi: 10.1016/j.biopha.2021.112100. Epub 2021 Aug 31.

Authors

Thiraphat Saengmearnuparp¹, Bannakij Lojanapiwat¹, Nipon Chattipakorn², Siriporn Chattipakorn³

Affiliations

¹ Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
² Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand.
³ Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand; Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: siriporn.c@cmu.ac.th.

PMID: 34479019
DOI: 10.1016/j.biopha.2021.112100

Abstract

Recent literature connects 5-alpha reductase inhibitors (5-ARIs) with neuropsychiatric adverse effects. Several clinical studies have indicated that former 5-ARIs users had a higher incidence of depressive symptoms and neuropsychiatric side effects than non-users. However, the underlying mechanisms involved in the depression in former 5-ARIs patients, a condition known as "post finasteride syndrome (PFS)", are not thoroughly understood. This review aims to summarize and discuss the association between 5-ARIs and depression as well as possible mechanisms. We used PubMed search terms including "depression", "depressive symptoms", "MDD", "anxiety", or "suicidal idea", and "5-alpha reductase inhibitors", "finasteride", "dutasteride", "5-ARIs". All relevant articles from in vivo and clinical studies from 2002 to 2021 were carefully reviewed. Any contradictory findings were included and debated. The potential mechanisms that link 5-ARIs and depression include alteration in neuroactive steroids, dopaminergic dysfunction, reduced hippocampal neurogenesis, increased neuroinflammation, alteration of the HPA axis, and epigenetic modifications. From this review, we hope to provide information for future studies based on animal experiments, and potential therapeutic strategies for depressive patients with PFS.

Keywords: 5-ARIs; Depression; Dopamine; Finasteride; Neuroactive steroids.

Publication types

Review

MeSH terms

5-alpha Reductase Inhibitors / administration & dosage
5-alpha Reductase Inhibitors / adverse effects*
Administration, Oral
Adult
Affect / drug effects*
Aged
Animals
Brain / drug effects*
Brain / physiopathology
Depression / chemically induced*
Depression / metabolism
Depression / physiopathology
Depression / psychology
Dopaminergic Neurons / drug effects
Female
Humans
Male
Middle Aged
Neurogenesis / drug effects
Neuroinflammatory Diseases / chemically induced
Neuroinflammatory Diseases / metabolism
Neuroinflammatory Diseases / physiopathology
Neurosteroids / metabolism*
Risk Assessment
Risk Factors
Time Factors

Substances

5-alpha Reductase Inhibitors
Neurosteroids