Cortisol response to diazepam: its relationship to age, dose, duration of treatment, and presence of generalized anxiety disorder
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Acute diazepam administration has been shown to decrease plasma cortisol levels consistent with decreased activity of the hypothalamic-pituitary-adrenal axis, especially in individuals experiencing stress. However, the effects of chronic diazepam treatment on cortisol have been less studied, and the relationship to age, anxiety, duration of treatment, and dose are not well understood.
This double-blind placebo-controlled study examined acute and chronic effects of diazepam on plasma cortisol levels in young (19–35 years) and elderly (60–79 years) individuals with and without generalized anxiety disorder (GAD). Subjects received single oral challenges of placebo or diazepam (2.5 mg or 10 mg) in a placebo-controlled cross-over design, followed by 3 weeks of chronic daily treatment with 2.5 mg or 10 mg diazepam or placebo taken at 10 p.m., and then by a final acute challenge with a single oral dose of the same study medication received during chronic treatment.
The elderly experienced significant reductions in plasma cortisol levels compared to placebo both in the initial challenge and during chronic treatment, but the young did not. However, cortisol response to drug was comparable in both groups. Final challenge did not produce any significant cortisol effects in either group and the cortisol response in the elderly was significantly reduced compared to the initial challenge. GAD status was not a factor in plasma cortisol responses to diazepam.
Diazepam reduced cortisol both acutely and during chronic treatment, but not during final challenge, consistent with some tolerance development. This effect was most apparent in the elderly compared with the young adults and was not modulated by GAD status or dosage, and was not related to drug effects on performance and on self-ratings of sedation and tension.
KeywordsDiazepam Cortisol Anxiety Elderly Benzodiazepines Age Acute Chronic Tolerance HPA axis
- Berchou R, Block RI (1989) Use of computerized psychomotor testing in determining CNS effects of drugs. Percept Motor Skills 57:691–700Google Scholar
- Collomp K, Fortier M, Cooper S, Long A, Ahmaidi S, Prefaut C, Wright F, Picot M, Cote MG (1994) Performance and metabolic effects of benzodiazepine during submaximal exercise. J Appl Physiol 77:828–833Google Scholar
- Goldstein DS, Dionne R, Sweet J, Gracely R, Brewer HB Jr, Gregg R, Keiser HR (1982) Circulatory, plasma catecholamine, cortisol, lipid, and psychological responses to a real-life stress (third molar extractions): effects of diazepam sedation and of inclusion of epinephrine with the local anesthetic. Psychosom Med 44:259–272PubMedGoogle Scholar
- Hommer DW, Matsuo V, Wolkowitz O, Chrousos G, Greenblatt DJ, Weingartner H, Paul SM (1986) Benzodiazepine sensitivity in normal human subjects. Arch Gen Psychiatry 43:542–551Google Scholar
- Newcomer JW, Selke G, Melson AK, Hershey T, Craft S, Richards K, Alderson AL (1999) Decreased memory performance in healthy humans induced by stress-level cortisol treatment. Arch Gen Psychiatry 56:527–533Google Scholar
- Roy-Byrne PP, Cowley DS, Hommer D, Ritchie J, Greenblatt D, Nemeroff C (1991) Neuroendocrine effects of diazepam in panic and generalized anxiety disorders. Biol Psychiatry 30:73–80Google Scholar
- Torpy DJ, Grice JE, Hockings GI, Walters MM, Crosbie GV, Jackson RV (1994) Alprazolam attenuates vasopressin-stimulated adrenocorticotropin and cortisol release: evidence for synergy between vasopressin and corticotropin-releasing hormone in humans. J Clin Endocrinol Metab 79:140–144Google Scholar