Long-Term Benzodiazepine Use and Salivary Cortisol

Manthey, Leonie; Giltay, Erik J.; Neven, Arie Knuistingh; Vreeburg, Sophie A.; Penninx, Brenda W. J. H.; Zitman, Frans G.

doi:10.1097/jcp.0b013e3181d41f41

Cited by 20 publications

(7 citation statements)

References 37 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, it is important to highlight that all patients were under benzodiazepines during this study and that half of them were already using them before the study. However, previous treatment with benzodiazepines did not predict CAR, corroborating some similar studies that did not observe changes in CAR induced by benzodiazepines (McIntyre et al, 1993;Manthey et al, 2010). Benzodiazepine modulation on the HPA axis is conflicting and dependent on the type of drug, dose, type of biological sample, and study design (Laakmann et al, 1984;Kalogeras et al, 1990;Pomara et al, 2005;Fries et al, 2006).…”

Section: Discussionsupporting

confidence: 78%

Changes in Cortisol but Not in Brain-Derived Neurotrophic Factor Modulate the Association Between Sleep Disturbances and Major Depression

Santiago

Galvão

Almeida

et al. 2020

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Sleep disturbance is a symptom consistently found in major depression and is associated with a longer course of illness, reduced response to treatment, increased risk of relapse and recurrence. Chronic insomnia has been associated with changes in cortisol and serum brain-derived neurotrophic factor (BDNF) levels, which in turn are also changed in major depression. Here, we evaluated the relationship between sleep quality, salivary cortisol awakening response (CAR), and serum BDNF levels in patients with sleep disturbance and treatment-resistant major depression (n = 18), and in a control group of healthy subjects with good (n = 21) and poor (n = 18) sleep quality. We observed that the patients had the lowest CAR and sleep duration of all three groups and a higher latency to sleep than the healthy volunteers with a good sleep profile. Besides, low CAR was correlated with more severe depressive symptoms and worse sleep quality. There was no difference in serum BDNF levels between groups with distinct sleep quality. Taken together, our results showed a relationship between changes in CAR and in sleep quality in patients with treatment-resistant depression, which were correlated with the severity of disease, suggesting that cortisol could be a physiological link between sleep disturbance and major depression.

show abstract

Section: Discussionsupporting

confidence: 78%

Changes in Cortisol but Not in Brain-Derived Neurotrophic Factor Modulate the Association Between Sleep Disturbances and Major Depression

Santiago

Galvão

Almeida

et al. 2020

Front. Behav. Neurosci.

View full text Add to dashboard Cite

show abstract

“…In our hands, we observed an ameliorating effect of imepitoin on cortisol levels in response to thunderstorm noises, but not for dexmedetomidine. Benzodiazepines were found to suppress cortisol levels ( Manthey et al, 2010 ), and thus these findings further support the benzodiazepine-like anxiolytic effect of imepitoin.…”

Section: Discussionmentioning

confidence: 55%

Imepitoin Shows Benzodiazepine-Like Effects in Models of Anxiety

Engel

Mašić²,

Landsberg³

et al. 2018

Front. Pharmacol.

View full text Add to dashboard Cite

Imepitoin is a low affinity partial agonist for the benzodiazepine binding site of γ-aminobutyric acid (GABAA) receptors, and is currently used as an antiepileptic in dogs. Here we tested imepitoin for anxiolytic properties. In an in vitro model, imepitoin was capable of preventing the effect of corticotrophin releasing factor (CRF) on locus coeruleus neurons without suppressing the basal activity of these cells, an activity which is suggestive for an anti-stress effect of imepitoin. In addition, we applied a battery of standard rodent preclinical tests for anxiety behavior including elevated plus mazes in mice and rats, light-dark-box in mice and rats, social interaction test in rats, or the Vogel conflict test in rats. In all models, the observed profile of imepitoin appeared similar to benzodiazepines and typical for anxiolytic drugs. We also observed anxiolytic activity in dogs in a provoked open field sound-induced fear model, where reactions to noises were elicited by a sound recording of thunderstorms. Imepitoin caused an increase in locomotion measured in distance traveled and an ameliorating effect on cortisol levels in response to thunderstorm noises. For comparison, dexmedetomidine caused a decrease in locomotion and had no effect on cortisol. In all animal models the doses needed for an anxiolytic effect were not associated with sedation. In rodents, there was at least a factor of 10 between anxiolytic doses and doses with mild signs of sedation. In summary, imepitoin showed similar anxiolytic activities as benzodiazepines but without producing the known adverse reactions of benzodiazepines such as sedation.

show abstract

“…As BZDs have anxioliytic and sedating properties, it is expected that they influence the stress system. Also, most studies showed a decrease in cortisol levels, 39–43 some studies reported mixed results, 43–45 and these inconsistencies may be explained by differences in patient groups, dosages, and BZD used among studies. 43 Some studies yield a reduction of variations in noradrenaline (NA) metabolite levels (MHPG) ‘noradrenergic volatility’, 46 and in circulating and salivary cortisol levels using alprazolam in anxious patients 22 39 41 and in normal subjects, 47 or also an increase in levels of dehydroepiandrosterone (an anticortisol mediator).…”

Section: Introductionmentioning

confidence: 99%

“…Also, most studies showed a decrease in cortisol levels, 39–43 some studies reported mixed results, 43–45 and these inconsistencies may be explained by differences in patient groups, dosages, and BZD used among studies. 43 Some studies yield a reduction of variations in noradrenaline (NA) metabolite levels (MHPG) ‘noradrenergic volatility’, 46 and in circulating and salivary cortisol levels using alprazolam in anxious patients 22 39 41 and in normal subjects, 47 or also an increase in levels of dehydroepiandrosterone (an anticortisol mediator). 48 Nevertheless, many controversial findings were made depending on age and gender: younger anxious patients showed higher levels of salivary cortisol awakening response, 13 18 but other authors found high salivary cortisol levels associated with severity of late-life generalised anxiety disorders in older adults.…”

Section: Introductionmentioning

confidence: 99%

Impact of alprazolam in allostatic load and neurocognition of patients with anxiety disorders and chronic stress (GEMA): observational study protocol

Soria¹,

Remedi²,

Núñez

et al. 2015

BMJ Open

View full text Add to dashboard Cite

IntroductionThe allostatic load model explains the additive effects of multiple biological processes that accelerate pathophysiology related to stress, particularly in the central nervous system. Stress-related mental conditions such as anxiety disorders and neuroticism (a well-known stress vulnerability factor), have been linked to disturbances of hypothalamo–pituitary–adrenal with cognitive implications. Nevertheless, there are controversial results in the literature and there is a need to determine the impact of the psychopharmacological treatment on allostatic load parameters and in cognitive functions. Gador study of Estres Modulation by Alprazolam, aims to determine the impact of medication on neurobiochemical variables related to chronic stress, metabolic syndrome, neurocognition and quality of life in patients with anxiety, allostatic load and neuroticism.Methods/analysisIn this observational prospective phase IV study, highly sympthomatic patients with anxiety disorders (six or more points in the Hamilton-A scale), neuroticism (more than 18 points in the Neo five personality factor inventory (NEO-FFI) scale), an allostatic load (three positive clinical or biochemical items at Crimmins and Seeman criteria) will be included. Clinical variables of anxiety, neuroticism, allostatic load, neurobiochemical studies, neurocognition and quality of life will be determined prior and periodically (1, 2, 4, 8, and 12 weeks) after treatment (on demand of alprazolam from 0.75 mg/day to 3.0 mg/day). A sample of n=55/182 patients will be considered enough to detect variables higher than 25% (pretreatment vs post-treatment or significant correlations) with a 1-ß power of 0–80. t Test and/or non-parametric test, and Pearson's test for correlation analysis will be determined.Ethics and disseminationThis study protocol was approved by an Independent Ethics Committee of FEFyM (Foundation for Pharmacological Studies and Drugs, Buenos Aires) and by regulatory authorities of Argentina (ANMAT, Dossier # 61 409–8 of 20 April 2009), following the law of Habeas Data and psychotherapeutic drug control.Trial registration numberGEMA 20811.

show abstract

Long-Term Benzodiazepine Use and Salivary Cortisol

Abstract: Despite the finding of slightly lower evening cortisol levels in daily and infrequent BZD users compared to nonusers, results indicate that long-term BZD use is not convincingly associated with HPA axis alterations.

Cited by 20 publications

References 37 publications

Changes in Cortisol but Not in Brain-Derived Neurotrophic Factor Modulate the Association Between Sleep Disturbances and Major Depression

Changes in Cortisol but Not in Brain-Derived Neurotrophic Factor Modulate the Association Between Sleep Disturbances and Major Depression

Imepitoin Shows Benzodiazepine-Like Effects in Models of Anxiety

Impact of alprazolam in allostatic load and neurocognition of patients with anxiety disorders and chronic stress (GEMA): observational study protocol

Contact Info

Product

Resources

About