Dehydroepiandrosterone for depressive symptoms: A systematic review and meta‐analysis of randomized controlled trials

Abstract

Depression is a mental disorder that affects millions of people around the world. However, depressive symptoms can be seen in other psychiatric and medical conditions. Here, we investigate the effect of DHEA treatment on depressive symptoms in individuals with depression and/or other clinical conditions in which depressive symptoms are present. An electronic search was performed until October 2019, with no restrictions on language or year of publication in the following databases: Medline, EMBASE, LILACS, and Cochrane Library. Randomized controlled trials comparing DHEA versus placebo were included if the depressive symptoms were assessed. Fifteen studies with 853 female and male individuals were included in this review. To conduct the meta-analysis, data were extracted from 14 studies. In comparison with placebo, DHEA improved depressive symptoms (standardized mean difference [SMD] −0.28, 95% (CI) −0.45 to −0.11, p =.001, 12 studies, 742 individuals (375 in the experimental group and 367 in the placebo group), I 2 = 24%), very low quality of evidence, 2 of 14 studies reporting this outcome were removed in a sensitivity analysis as they were strongly influencing heterogeneity between studies. No hormonal changes that indicated any risk to the participants' health were seen. Side effects observed were uncommon, mild, and transient, but commonly related to androgyny. In conclusion, DHEA was associated with a beneficial effect on depressive symptoms compared to placebo. However, these results should be viewed with caution, since the quality of evidence for this outcome was considered very low according to the GRADE criteria.

Dehydroepiandrosterone sulfate indicates decreased sulfation capacity and impaired quality of life in Primary Sclerosing Cholangitis

“…As patients with PBC and PSC both share clinical symptoms affecting HRQoL, including pruritus and chronic fatigue, PBC-40 has been found to be a useful tool for assessing HRQoL in PSC as well [20]. Of importance, PBC-40 also assesses cognitive dysfunction, previously found to be impaired in patients with various conditions and low DHEA-S [25]. Our study clearly showed an association between decreased DHEA-S and low HRQoL.…”

“…DHEA-S itself has been widely advertised as an over-the-counter supplement that can improve various symptoms related to different conditions, including depression and mood disorders, osteoporosis, adrenal insufficiency, and rheumatoid arthritis [15]. Data in support of these claims remain controversial, with numerous meta-analyses producing inconclusive results [23][24][25][26]. Supplementation with DHEA had a positive effect on the HRQoL in small groups of patients with systemic lupus erythematosus and hypopituitarism [27,28].…”

Cerebral perfusion in depression: Relationship to sex, dehydroepiandrosterone sulfate and depression severity

“…Higher baseline DHEAS serum concentration was also identified as a predictor for SSRI response in MDD patients ( Hough et al, 2017 ). In their meta -analysis, Peixoto et al (2020) also proposed DHEAS as a possible treatment in itself, demonstrating a significant effect of the neurosteroid when compared to placebo, possibly acting via GABA-ergic modulation ( Genud et al, 2009 ). This difference in baseline DHEAS concentration and its interaction with baseline perfusion might, in part, account for the higher prevalence of MDD in women and act protectively in women with higher DHEAS concentrations than the average.…”

“…In a previous study investigating the effect of neurosteroid levels on perfusion, plasma concentrations of the neurosteroid dehydroepiandrosterone sulfate (DHEAS) were observed to explain some of the variance in global and regional brain perfusion between men and women ( Ghisleni et al, 2015 ). Since DHEAS has been linked to anxiety ( Hsiao, 2006 ) and depressive symptoms ( Peixoto et al, 2020 , Souza-Teodoro et al, 2016 , ter Horst et al, 2019 ), and shows significant sex differences ( Leblhuber et al, 1993 , Orentreich et al, 1984 ), perfusion and DHEAS may represent potential mediators for differences in depression vulnerability between men and women. However, to date, the interaction between sex and perfusion on depression has not been examined directly, and it is not yet known to what extent DHEAS may mediate the relationship between perfusion and depressive symptoms.…”

Wait-there’s evidence for that? Integrative medicine treatments for major depressive disorder

“…5,6 Given that the evidence is still low, and there are more side effects compared to many treatments listed here, such as acne, hypertension, and effects on the liver, DHEA can be considered an alternative treatment for monotherapy or adjunctive therapy in major depression, although other agents discussed here such as St. John’s Wort, Omega-3 Fatty Acids, methylfolate, and saffron have more evidence and fewer side effects. 14…”