Alprazolam increases dehydroepiandrosterone concentrations

The gamma-aminobutyric acid (GABA) agonist alprazolam is known to decrease adrenocorticotropic hormone and cortisol concentrations. Dehydroepiandroste rone (DHEA) is secreted synchronously with cortisol by the adrenal glands a nd demonstrates diurnal variation. The major objective of this study was to determine whether alprazolam affects concentrations of DHEA and DHEA-S, th e sulfated metabolite. In vitro studies have demonstrated that DHEA-S, and perhaps DHEA, have GABA antagonistic activity. Another objective was to det ermine whether DHEA-S and/or DHEA concentrations are related to psychomotor impairment after alprazolam. Thirty-eight healthy volunteers (25 young men , aged 22-35, and 13 elderly men, aged 65-75) received a single intravenous dose of alprazolam 2 mg/2 min (part 1). Fifteen young and 13 elderly men r esponded to alprazolam and agreed to participate in part 2 of the study, wh ich was a crossover of placebo and alprazolam infusion to plateau for 9 hou rs. Plasma samples at 0, 1, 4, and 7 hours were assayed for steroid concent rations. Alprazolam produced (1) significant increases in DHEA concentratio ns at 7 hours in both young and elderly men; (2) significant decreases in c ortisol concentrations; and (3) no change in DHEA-S concentrations. The rel ationship between psychomotor decrement and DHEA concentrations at 7 hours after alprazolam 2 mg/2 min was described by a u-shaped curve (p < 0.0047). Both the linear and quadratic components of the equations for the tests we re significant (p < 0.002). These results suggest that alprazolam modulates peripheral concentrations of DHEA and that DHEA and/or DHEA-S may have an In vivo role in modulating GABA receptor-mediated responses.