Cortisol response to diazepam: Its relationship to age, dose, duration of treatment, and presence of generalized anxiety disorder. Psychopharmacology, 178, 1-8

Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Building 35, Orangeburg, NY 10962, USA.
Psychopharmacology (Impact Factor: 3.88). 03/2005; 178(1):1-8. DOI: 10.1007/s00213-004-1974-8
Source: PubMed


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.

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    • "The effects of diazepam and fluoxetine on cortisol levels have been previously reported in other species. For example, diazepam has been shown to decrease plasma cortisol levels, especially in humans experiencing stress [45]. Another study in elephant seals (Mirounga angustirostris) found that when animals were sedated with a combination of drugs ([tiletamine hydrochloride 50 mg/mL, zolazepam hydrochloride 50 mg/mL], ketamine, and diazepam) in the field, they did not exhibit a cortisol stress response. "
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    PLoS ONE 07/2014; 9(7):e103232. DOI:10.1371/journal.pone.0103232 · 3.23 Impact Factor
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    • "Taken together, these findings suggest that cortisol may indeed play an important role in the facilitation of extinction learning. A major consideration in furthering the development of glucocorticoids as an adjunct to extinction-based therapies is the notion that many anxiolytic medications suppress cortisol or hinder cortisol reactivity (Fries et al., 2006; Pomara et al., 2005). Therefore, the attenuation of glucocorticoid activity by anxiolytic medications may actually interfere with extinction learning during exposure-based treatments, which may reduce the benefits of combining treatment modalities between CBT and medications (Otto, McHugh et al., 2010). "
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    • "The observed inhibitory effect of 2.0 mg/kg diazepam on the HPA axis activity agrees with our previous studies that used the same (21) or similar (20,26) doses and timing of diazepam administration, but disagrees with some results which demonstrated no changes in the levels of corticosterone induced by diazepam treatment (23). Some of the discrepancies considering the effects of diazepam on the basal HPA activity (stimulation, inhibition, or no effect) could be ascribed to the differences in sex (15,20,28,38), age (13,39), basal vs stressful conditions (10,13,38), or the strain of the animals used (40). "
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