DHEA is effective against depressed mood but not cognitive impairment or psychosis

What it is and how it works in the brain

Dehydroepiandrosterone (DHEA) is a precursor of testosterone and other hormones. The sulfated form of DHEA—DHEA-S—is the most abundant steroid in the body. DHEA is an important neuroactive steroid and modulates neuronal excitability by acting as an antagonist at the GABA receptor complex. Preclinical animal studies suggest that mood-enhancing effects of DHEA are mediated through androgen receptors, estrogen receptors, serotonin, GABA, NMDA, and possibly norepinephrine. DHEA’s antipsychotic effects may involve increased dopamine release in the frontal cortex and increased activity of NMDA and sigma receptors.

DHEA for depressed mood

In a small six-week study (22 subjects), depressed patients were randomized to DHEA in an escalating dose (30 mg per day for two weeks, followed by 30 mg twice daily for two weeks and 30 mg thrice daily for two weeks) versus placebo. Half of the patients in the DHEA group improved by 50 percent or more on standardized rating scales. In a six-week placebo-controlled trial (46 subjects), moderately depressed adults off antidepressants were randomized to 90 mg per day of DHEA for three weeks, followed by 450 mg per day of DHEA (150 mg thrice daily) for three weeks versus placebo. The majority taking DHEA reported a 50 percent or greater reduction in depressive symptoms and improved sexual functioning. Most patients who responded to DHEA remained asymptomatic at the 12 months follow-up. More studies are needed to replicate these findings, evaluate DHEA for severe depressed mood, and clarify the mechanism for a putative synergistic or independent antidepressant effect. In a small placebo-controlled trial (30 subjects), inpatients with schizophrenia treated with 100 mg per day of DHEA in addition to their conventional antipsychotic medications experienced significant improvements in depressed mood, anxiety, and negative psychotic symptoms. Women improved more than men, and serum cortisol levels did not change during treatment.

DHEA for cognitive decline in normal aging

DHEA is used in Europe and North America to self-treat decline in cognitive functioning associated with normal aging, however, limited research findings support this use. Small pilot studies suggest that DHEA (25 to 50 mg per day) improves memory and enhances general cognitive functioning in healthy adults. However, most findings are inconsistent, and negative findings have been reported at doses less than 90 mg per day. A systematic review of studies on DHEA or DHEA-S in healthy older adults found no evidence of improved memory or cognitive functioning. Large studies of at least one year or longer are needed to fully explore claims of long-term beneficial effects of DHEA.

DHEA for dementia

DHEA may improve memory in elderly patients who have low DHEA serum levels more than in healthy adults with normal serum levels. However, no correlations were found between serum DHEA-S levels and severity of cognitive impairment or cumulative mortality in a large cohort of individuals newly diagnosed with Alzheimer disease. Preliminary findings suggest that 200 mg per day of DHEA may improve symptoms of cognitive impairment in multi-infarct dementia. However, no controlled trials on DHEA in Alzheimer disease have been completed. In a six-month placebo-controlled trial (47 subjects), men with mild dementia and healthy men aged 50 years and older were randomized to receive 75 mg of testosterone (in the form of a dermal gel) versus placebo together with their usual medications. Quality-of-life measures improved in men with mild dementia and healthy men taking testosterone, and fewer men with mild dementia who received testosterone experienced declines in overall functioning and visuospatial abilities.

DHEA for schizophrenia

In a six-week placebo-controlled trial (30 subjects), inpatients diagnosed with schizophrenia randomized to DHEA at 100 mg per day in addition to their regular antipsychotic medications experienced significant improvements in negative psychotic symptoms, including reduced apathy and social withdrawal. However, there were no significant changes in positive psychotic symptoms, including auditory hallucinations and delusions. Findings of another small study (30 subjects) suggest that augmentation of antipsychotics with DHEA (100 mg day for six weeks) may significantly reduce negative symptoms and may be especially effective in women. However, a systematic review of three small placebo-controlled studies (126 total subjects) on DHEA or testosterone as adjunctive therapies to antipsychotics found equivocal evidence for an augmentation effect on measures of positive and negative symptoms, global functioning, and quality of life.

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