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: 3.99). 03/2005; 178(1):1-8. DOI: 10.1007/s00213-004-1974-8
Source: PubMed

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.

  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Traditional treatments for anxiety disorders include cognitive-behavioral therapy and anxiolytic medications. Although these treatments are more effective than placebo, there is still considerable room for further improvement. Unfortunately, combining these different modalities is generally not substantially better than monotherapies. Recently, researchers have turned their attention toward translating preclinical research on the neural circuitry underlying fear extinction to clinical applications for the treatment of anxiety disorders with the goal to augment the learning process during exposure-based procedures with cognitive enhancers. This review examines d-cycloserine, cortisol, catecholamines, yohimbine, oxytocin, modafinil, as well as nutrients and botanicals as agents to augment treatment for anxiety disorders. D-cycloserine shows the most empirical support. Other promising agents include cortisol, catecholamines, yohimbine, and possibly oxytocin. Less support comes from studies that examined nutrients and botanicals, such as caffeine, nicotine, and omega-3 fatty acid. Limitations of the exiting literature and future research directions are discussed.
    Restorative neurology and neuroscience 03/2013; 32(1). DOI:10.3233/RNN-139002 · 4.18 Impact Factor
  • Source
    • "When tested in the presence of a stressor, acute treatment with citalopram resulted in enhanced CORT release in a rat restraint stressor paradigm (Hesketh et al., 2005). In contrast, BZ-type drugs can attenuate adrenocorticotropin hormone (ACTH), CORT or cortisol levels, particularly following exposure to an anxiogenic stressor (Carrasco and Van de Kar, 2003; Fries et al., 2006; Kalin et al., 1987; Kalman et al., 1997; Pivac and Pericic, 1993; Pomara et al., 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Selective serotonin re-uptake inhibitors (SSRIs), which are used commonly to treat anxiety disorders, have characteristic anxiogenic effects following acute administration. Treatment with anxiolytic benzodiazepines (BZs) may reduce these effects, although little is known about potential drug interactions. Our study evaluated acute anxiogenic-like effects of SSRIs, alone and combined with a BZ. Adult male BALB/c mice received fluoxetine (3.0-30.0mg/kg, i.p.) or citalopram (3.0-30.0mg/kg, i.p.) alone or in combination with diazepam (0.3-10.0mg/kg, i.p.), after which they were evaluated with the light/dark and open-field tests for anxiogenesis/anxiolysis. In addition, release of the stress hormone corticosterone was assessed following combined SSRI/BZ administration. In the light/dark and open-field tests, acute SSRIs produced a behavioral profile consistent with anxiogenesis, while diazepam produced an anxiolytic-like profile. Pre-treatment with diazepam (0.3-10mg/kg) reversed the effects of an anxiogenic-like dose of an SSRI (18mg/kg fluoxetine, 30mg/kg citalopram) in both light/dark and open-field tests. Diazepam, fluoxetine or citalopram, and their combination all significantly increased plasma corticosterone levels to the same degree. These findings suggest that a BZ-type drug can attenuate acute anxiogenic-like effects of an SSRI via a mechanism independent of corticosterone regulation.
    Pharmacology Biochemistry and Behavior 03/2011; 98(4):544-51. DOI:10.1016/j.pbb.2011.03.006 · 2.82 Impact Factor
  • Source
    • "The main result of the current study is that lower hair cortisol levels were found in GAD patients than in healthy control participants. This finding stands in contrast to previous research suggesting that GAD is associated with elevated basal cortisol levels in saliva (Mantella et al., 2008) as well as in plasma (Schweizer et al., 1986; Tiller et al., 1988; Pomara et al., 2005; Tafet et al., 2005). Similarly, the current hair cortisol finding is also inconsistent with evidence suggesting no alteration of basal cortisol secretion in GAD (Rosenbaum et al., 1983; Hoehn-Saric et al., 1991; Kelly and Cooper, 1998). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous research examining hypothalamic-pituitary-adrenal (HPA) axis activity in generalised anxiety disorder (GAD) has suggested a general hypercortisolism. These studies have mostly relied on salivary, plasma or urinary assessments, reflecting cortisol secretion over short time periods. The current study utilised the novel method of cortisol assessment in hair to obtain a retrospective index of cortisol secretion over a prolonged period of time. Hair cortisol levels were determined in 15 GAD patients and in 15 age- and gender-matched controls. In addition, participants collected six saliva samples (on awakening, +30 min, 12:00, 16:00, 20:00 h and at bedtime) on two consecutive weekdays for the assessment of the diurnal cortisol profile. Results revealed significantly lower (50-60%) cortisol levels in the first and second 3-cm hair segments of GAD patients compared to those of controls. No significant between-group differences were seen in diurnal cortisol profiles. The hair cortisol findings tentatively suggest that under naturalistic conditions GAD is associated with hypocortisolism. If corroborated by future research, this demonstrates the important qualities of cortisol measurement in hair as an ecologically valid, retrospective index of long-term cortisol secretion and as a marker for psychiatric disorders associated with hypo- or hypercortisolism.
    Psychiatry Research 10/2010; 186(2-3):310-4. DOI:10.1016/j.psychres.2010.09.002 · 2.68 Impact Factor
Show more