Dehydroepiandrosterone (DHEA) augmentation in the management of schizophrenia symptomatology.

Neurosteroids, such as dehydroepiandrosterone (DHEA) and DHEA-sulfate (the most abundant steroid in the body), regulate neuronal functions by influencing neuronal excitability. Prominent effects are exerted on the gamma-aminobutyric (GABA) receptors. DHEA has demonstrated efficacy in improvement of mood in humans, especially in middle-aged and elderly individuals. In the author's study, administering DHEA to patients with schizophrenia who had moderate to severe negative symptoms and who were maintained on antipsychotic medications induced significant improvement, more so in women and corresponding to increased plasma levels of DHEA and DHEA-S. Possible mechanisms of action include enhanced dopamine release, enhanced responsiveness at the N-methyl D-aspartate (NMDA) receptor, facilitation of sigma receptor activity, selective potentiation of dopaminergic neurotransmission, and a general anxiolytic action. Side effects are reviewed, and the currently experimental status of DHEA augmentation is emphasized.