Cortisol response to diazepam: its relationship to age, dose, duration of treatment, and presence of generalized anxiety disorder.
ABSTRACT 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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ABSTRACT: Evidence of aberrant hypothalamic-pituitary-adrenocortical (HPA) activity in many psychiatric disorders, although not universal, has sparked long-standing interest in HPA hormones as biomarkers of disease or treatment response. HPA activity may be chronically elevated in melancholic depression, panic disorder, obsessive-compulsive disorder, and schizophrenia. The HPA axis may be more reactive to stress in social anxiety disorder and autism spectrum disorders. In contrast, HPA activity is more likely to be low in PTSD and atypical depression. Antidepressants are widely considered to inhibit HPA activity, although inhibition is not unanimously reported in the literature. There is evidence, also uneven, that the mood stabilizers lithium and carbamazepine have the potential to augment HPA measures, while benzodiazepines, atypical antipsychotics, and to some extent, typical antipsychotics have the potential to inhibit HPA activity. Currently, the most reliable use of HPA measures in most disorders is to predict the likelihood of relapse, although changes in HPA activity have also been proposed to play a role in the clinical benefits of psychiatric treatments. Greater attention to patient heterogeneity and more consistent approaches to assessing treatment effects on HPA function may solidify the value of HPA measures in predicting treatment response or developing novel strategies to manage psychiatric disease. © 2014 American Physiological Society. Compr Physiol 4:715-738, 2014.04/2014; 4(2):715-38. DOI:10.1002/cphy.c130036
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ABSTRACT: The presence of pharmaceutical products in the aquatic environment has been reported in several studies. However, the impact of these drugs on living organisms is still uncharacterized. Here, we investigated the effects of acute exposure to either diazepam or fluoxetine on the stress response in Danio rerio. We showed that diazepam and fluoxetine inhibited the stress axis in zebrafish. Intermediate concentrations of diazepam suppressed the stress response as measured by cortisol levels, whereas fluoxetine inhibited cortisol increase at concentrations similar to those found in the environment. These data suggest that the presence of psychoactive drugs in aquatic ecosystems could cause neuroendocrine dysfunction in fish.PLoS ONE 07/2014; 9(7):e103232. DOI:10.1371/journal.pone.0103232 · 3.53 Impact Factor
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ABSTRACT: Research into the role of the HPA system in mental disorders has recently increased. It has been found that hormones involved in regulation of the HPA system play an important role in stress-related disorders. In the past, baseline alterations were mainly inspected in patients with anxiety disorders. In order to assess changes concerning the acute stress reaction in these subjects, many studies also applied stress protocols such as pharmacological or nonpharmacological challenges. This review aims to provide an overview of the results regarding HPA function in various anxiety disorders, such as panic disorder, generalized anxiety disorder, social anxiety disorder, specific phobia, obsessive-compulsive disorder and post-traumatic stress disorder. A PubMed-based literature search revealed 59 studies that met the inclusion criteria (i.e., double-blind randomized placebo-controlled trial; diagnosis based on DSM-III or -IV; and appropriate sample size - n >= 20 in the verum group). Results are presented and integrated with regard to baseline HPA system activation and response to a challenge. Markers of interest reporting on HPA system functioning were cortisol and adrenocorticotropic hormone. In addition, suggested explanations regarding pathophysiological mechanisms underlying these findings are discussed. The majority of current data do not point to an alteration of the HPA system in anxiety disorders. There is some evidence for an association between the magnitude of mental stress and a change in cortisol levels. Nevertheless, pharmacotherapeutical interventions affecting stress hormones might be promising, not only in augmentation of psychotherapy in a specific phobia, but also for secondary prevention in post-traumatic stress disorder.Neuropsychiatry 02/2013; 3(1):1-18. DOI:10.2217/npy.13.6