, Volume 178, Issue 1, pp 1–8

Cortisol response to diazepam: its relationship to age, dose, duration of treatment, and presence of generalized anxiety disorder

  • Nunzio Pomara
  • Lisa M Willoughby
  • John J Sidtis
  • Thomas B Cooper
  • David J Greenblatt
Original Investigation



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.


Diazepam Cortisol Anxiety Elderly Benzodiazepines Age Acute Chronic Tolerance HPA axis 


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Nunzio Pomara
    • 1
    • 2
  • Lisa M Willoughby
    • 1
  • John J Sidtis
    • 1
    • 2
  • Thomas B Cooper
    • 1
    • 2
    • 3
  • David J Greenblatt
    • 4
  1. 1.Nathan Kline Institute for Psychiatric ResearchOrangeburgUSA
  2. 2.Department of PsychiatryNew York University School of MedicineNew YorkUSA
  3. 3.Analytical Psychopharmacology Laboratories, New York State Psychiatric Institute and Department of Psychiatry, College of Physicians & SurgeonsColumbia UniversityNew YorkUSA
  4. 4.Department of Pharmacology & Experimental TherapeuticsTufts University School of MedicineBostonUSA

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