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

Abstract

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.

Walking the Tightrope: A Proposed Model of Chronic Pain and Stress

“…This model supports recent findings from our group (Sieberg et al, 2018). We examined the effects of lifelong mild stress on levels of neuropathic pain and the effects of chronic neuropathic injury on anxiety-like behavior in mice with results demonstrating a strong link between chronic neuropathic pain and chronic anxiety (Soria et al, 2015), with the driver of this comorbidity being neuropathic pain as opposed to ongoing stress (Sieberg et al, 2018). However, the timing, severity, and type of stress needed to induce this cruel cycle is unclear, and alternatively, if there is a healthy or protective dose of stress that could buffer or prevent the onset of chronic pain, or how much stress is protective is also unknown.…”

Sex and Age-Related Differences in Neuroticism and Allostatic Load Index in Urban Patients with General Anxiety Disorder Treated with Alprazolam

“…Controlled studies will be performed in the coming steps and different goals. In this study we did not report the cognitive variables (described in the original protocol and still under analysis) [27], which are planned for future evaluation. Furthermore, as a significant reduction in the total AL index was observed and many AL variables were significantly reduced after treatment, in this open study other non-pharmacological factors may also be considered to be interacting during treatment.…”

“…This report is part of the preliminary results of the GEMA study protocol, which has been discussed in detail in a previous publication [27]. In this open and prospective study volunteer patients were recruited since September 2011 until May 2014, after signing the informed consent.…”

“…Statistical significance was considered at p < 0.05 (2-sided; 1-β power ≥ 0.80). The sample size was calculated in (n = 29 -55) cases, with the aim to detect changes in variables higher than 25% with a 1-β power of 0 -80 [27].…”

Semantic and Phonemic Verbal Fluency Performance in Patients with General Anxiety Disorders and Allostatic Load under Alprazolam Treatment

“…The rate of the outpatients' use of benzodiazepines has been increased substantially in the last years, especially among clinicians, psychiatrists and neurologists [20]; indeed clinical studies are continually needed to determine safety in long term uses. The GEMA project (Gador Study of Stress Modulation by Alprazolam) [21] consists of a series of consecutive studies performed on a group of high symptomatic outpatients with general anxiety disorder (GAD) 2 associated with chronic stress, determined by high allostatic load (AL) levels (indicators for the functioning of the main potentially stress affected systems) [22] [23] and neuroticism (a clinical condition well-known as a stress vulnerability factor and defined as an exaggerated response to psychosocial stressors with intense emotional reaction) [ In a previous analysis performed by our group in the same cohort of patients, we analyzed the AL index and determined the effects of sex and age on allostatic load variables before and after treatment [28]. In this study we found that female sex was associated with higher levels of anxiety with a better profile in the same allostatic load variables such as cardiovascular ones.…”