Alprazolam Increases Dehydroepiandrosterone Concentrations

Abstract

The gamma-aminobutyric acid (GABA) agonist alprazolam is known to decrease adrenocorticotropic hormone and cortisol concentrations. Dehydroepiandrosterone (DHEA) is secreted synchronously with cortisol by the adrenal glands and demonstrates diurnal variation. The major objective of this study was to determine whether alprazolam affects concentrations of DHEA and DHEA-S, the sulfated metabolite. In vitro studies have demonstrated that DHEA-S, and perhaps DHEA, have GABA antagonistic activity. Another objective was to determine 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 responded to alprazolam and agreed to participate in part 2 of the study, which was a crossover of placebo and alprazolam infusion to plateau for 9 hours. Plasma samples at 0, 1, 4, and 7 hours were assayed for steroid concentrations. Alprazolam produced (1) significant increases in DHEA concentrations at 7 hours in both young and elderly men; (2) significant decreases in cortisol concentrations; and (3) no change in DHEA-S concentrations. The relationship 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 were 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.

Cortisol/Dehydroepiandrosterone Ratio and Responses to Antipsychotic Treatment in Schizophrenia

“…Benzodiazepines also can affect concentrations of DHEA(S). For example, alprazolam (GABA agonist) produced significant increases in DHEA, reduction in cortisol, and no change in DHEAS concentrations (Kroboth et al, 1999). Findings from the present study suggest that benzodiazepines did not influence the elevation of serum cortisol levels, and molar cortisol/DHEA(S) ratios among the responders compared with nonresponders.…”

The Influence of Hormones and Pharmaceutical Agents on DHEA and DHEA‐S Concentrations: A Review of Clinical Studies

“…To date, alprazolam is the only drug from the benzodiazepine class that has been evaluated for its effects on DHEA and DHEA-S in humans. 106,107 Alprazolam 2 mg/2 min was administered intravenously to 38 healthy men (25 young men, ages 22-35; 13 elderly men, ages [65][66][67][68][69][70][71][72][73][74][75]. Plasma samples were obtained at baseline and 1, 4, and 7 hours after alprazolam administration to determine DHEA, DHEA-S, and cortisol concentrations.…”

Antidepressant Treatment and Dehydroepiandrosterone Sulfate: Different Effects of Amitriptyline and Paroxetine

“…Acute treatment with benzodiazepines may increase DHEA, although not DHEA-S concentrations [22]. Therefore, we cannot exclude that the different amount of benzodiazepines contributed to our findings.…”