DHEA for Depression

DHEA (dehydroepiandrosterone, an adrenal hormone sold over the counter) has a small, mostly positive but very low-quality body of evidence for depression. Pooling 12 placebo-controlled trials in 742 people, a 2020 meta-analysis found DHEA improved depressive symptoms by a small amount (standardised mean difference -0.28, 95% CI -0.45 to -0.11), and graded the evidence very low quality (Peixoto 2020).

The individual trials point the same way but are tiny: 22 adults with major depression, 46 with midlife-onset depression and 15 completers with dysthymia (Wolkowitz 1999; Schmidt 2005; Bloch 1999). They gave up to 90 mg a day, rising to 450 mg in two trials, for only 6 weeks of treatment. In healthy older adults, 50 mg a day for a year did not change depression scores (Kritz-Silverstein 2008). That makes DHEA an unproven option, not a treatment to try on your own.

DHEA is one of the body's main precursors of androgens, which are then converted into testosterone and estrogens (Scheffers 2015). It is also a neurosteroid: it acts in the brain and helps regulate how excitable nerve cells are (Strous 2003). Both routes could plausibly affect mood.

People with depression tend to have lower blood DHEA-S (the sulfated, circulating form) than healthy controls. A case-control study with a meta-analysis found levels were clearly lower in depressed patients (SMD 0.777 in favour of controls) and fell with age (Zhu 2015). Lower levels in depression are one reason researchers have been interested in DHEA as an antidepressant.

A low level in people with depression doesn't show that raising it treats depression; low DHEA-S could be a result of depression or of age. A 2024 Mendelian randomisation study (which uses genes to test cause and effect) of antidepressant response gave mixed results: no effect from the combined gene score, but signals from three single variants that the authors read as some evidence of a causal link (Souza-Teodoro 2024).

The trials don't settle it either. In schizophrenia, rising DHEA levels tracked improvement in negative symptoms but not in depressive symptoms (Strous 2003). Because DHEA becomes testosterone and estrogen, any mood effect may also come through those hormones.

The positive depression trials used high doses. One gave up to 90 mg a day for 6 weeks (Wolkowitz 1999). Two crossover trials gave 90 mg a day for 3 weeks, then 450 mg a day for 3 weeks (Schmidt 2005; Bloch 1999); in the dysthymia trial, a significant response was already seen after 3 weeks at 90 mg. The HIV trial let doctors adjust the dose between 100 and 400 mg a day over 8 weeks (Rabkin 2006).

The one long trial used a lower dose, 50 mg a day for a year, and found no difference from placebo on depression scores in healthy older adults (Kritz-Silverstein 2008). No trial has established a safe, effective dose for treating depression yourself, and these amounts change hormone levels, so they belong under a clinician's supervision.

The broadest review pooled randomised placebo-controlled trials of DHEA in people with depression or with depressive symptoms from other conditions: 15 studies and 853 participants, of which 12 trials (742 people) fed the main analysis. DHEA improved depressive symptoms with an SMD of -0.28 (95% CI -0.45 to -0.11, P=.001, I² 24%), a small effect, after two trials that drove heterogeneity were removed. The authors rated the quality of evidence very low by GRADE criteria and urged caution (Peixoto 2020).

An earlier review by the same group, limited to people whose depression was not caused by another condition, also found a significant effect in favour of DHEA, but its abstract gives no pooled numbers (Peixoto 2018). In women with adrenal insufficiency, a separate meta-analysis of 10 trials found a small benefit for depression that the authors called perhaps trivial (Alkatib 2009).

In 22 adults with major depression, DHEA up to 90 mg a day for 6 weeks lowered Hamilton depression scores more than placebo, and 5 of 11 on DHEA improved by half or more, against none of 11 on placebo (Wolkowitz 1999). In a double-blind crossover trial in 46 men and women aged 45-65 with midlife-onset major or minor depression and no antidepressants, 6 weeks of DHEA improved Hamilton and self-rated depression scores compared with placebo (both P<.01); 23 people improved by half or more on DHEA versus 13 on placebo (Schmidt 2005).

A crossover pilot by the same NIMH group in 17 adults with midlife-onset dysthymia (chronic low-grade depression) found 60% of the 15 completers responded to DHEA against 20% on placebo. Anhedonia (loss of pleasure), low energy and lack of motivation improved most (Bloch 1999).

The largest trial was in 145 adults with HIV/AIDS and persistent non-major depression or dysthymia. On 100-400 mg a day for 8 weeks, 56% responded on DHEA versus 31% on placebo by intent to treat, a number needed to treat of 4, with few side effects and no change in CD4 count or viral load (Rabkin 2006).

In 30 inpatients with schizophrenia taking antipsychotics, DHEA up to 100 mg a day for 6 weeks improved depressive symptoms (P<.05) as a secondary outcome, along with negative symptoms and anxiety (Strous 2003). These results may not apply to people with depression alone.

In the 1-year DAWN trial, 225 healthy adults aged 55-85 took 50 mg of DHEA or placebo. Depression scores fell over time in both groups, with no difference between them, and no effect on quality of life or life satisfaction (Kritz-Silverstein 2008). A Cochrane review of menopausal women found DHEA did not improve quality of life (SMD 0.16, 95% CI -0.03 to 0.34) (Scheffers 2015).

What's missing: a large trial in major depression, any head-to-head comparison with an antidepressant, follow-up beyond a few weeks at antidepressant-level doses, and independent replication of the midlife trials, two of which came from one group. The 2016 CANMAT guideline recommended exercise, light therapy, St John's wort, omega-3, SAM-e and yoga as first- or second-line options for mild to moderate depression, and left other natural products such as DHEA to third-line consideration (Ravindran 2016). For a supplement with better guideline support, the first- and second-line options in that guideline include St John's wort and omega-3.

Across trials in depression and in other conditions with depressive symptoms, side effects were uncommon, mild and short-lived, and were often androgenic (male-hormone effects) (Peixoto 2020). In menopausal women, DHEA made androgenic side effects, mainly acne, more likely than placebo (odds ratio 3.77, 95% CI 1.36 to 10.4) (Scheffers 2015). The trials lasted weeks to a year, so long-term safety at high doses is unknown.

The more serious concern is mania. Case reports describe mania in an older man with no bipolar history taking 200-300 mg a day for 6 months (Markowitz 1999), and severe mania in a 31-year-old man several weeks after starting DHEA (Dean 2000). That man had once been given an unconfirmed bipolar diagnosis. Dean suggested possible risk factors: high doses, a history of mood disorder, alcohol or street drugs, and antidepressants, and warned that people under 35 may be at particular risk.

No formal drug-interaction studies of DHEA and antidepressants were found. One small trial added DHEA to stable antidepressants (Wolkowitz 1999), and the author of a case report lists antidepressants among possible risk factors for DHEA-related mania (Dean 2000). Because DHEA is converted into testosterone and estrogens (Scheffers 2015), it adds to hormone therapy and can work against treatments that block those hormones. DHEA (prasterone) is on the World Anti-Doping Agency's prohibited list as an anabolic agent, banned at all times (WADA 2026).