Alterations of the HPA Axis Observed in Patients with Major Depressive Disorder and Their Relation to Early Life Stress: A Systematic Review.

BACKGROUND: Alterations of the hypothalamic-pituitary-adrenal (HPA) axis are common in patients diagnosed with major depressive disorder (MDD). Nevertheless, these alterations are not found in every patient. There is evidence to indicate a possible mediating role of early life stress (ELS) in the relation between dysfunction of the HPA axis and MDD. We conducted a systematic review to understand if the alterations of the HPA axis commonly found in patients with MDD are due to early life stress or are caused by the disorder itself. METHODS: The review was conducted by following the PRISMA guidelines. Original articles were found in PubMed and via a manual search. Only studies whose design allowed comparison of the HPA functioning in the 4 groups no-MDD/no-ELS, MDD/no-ELS, no-MDD/ELS, and MDD/ELS were included. RESULTS: Hyperactivity or hypoactivity of the HPA axis was found in 8 articles. A greater number of abnormalities and a higher rate of posttraumatic stress disorder comorbidity were found in the MDD/ELS group. Dysfunction of the HPA axis was also found in the no-MDD/ELS groups. CONCLUSION: HPA dysfunction found in MDD seems to be more related to the presence of ELS rather than to the MDD itself. Future studies are needed to clarify the exact mechanisms involved.

Overdosing of benzodiazepines/Z-drugs and falls in older adults: Costs for the health system.

INTRODUCTION: Benzodiazepines and Z drugs (BZD/Z drugs) are commonly used for the treatment of insomnia and anxiety in older adults for long periods of time. Given the physiological and metabolic characteristics of this group of patients, they are more prone to the adverse effects of these drugs which include falls. The recommendations for use of BZD/Z drugs include the need to adjust the dose and select those with a short half-life, to avoid adverse events, which as well as potentially affecting patient outcome, increase healthcare costs. In this study, we have evaluated the hospital-related costs associated with falls in older adults who use BZD/Z drugs at doses higher than recommended for this age group. METHODS: We conducted a cross-sectional observational study assessing the BZD/Z drug prescriptions of older adults attending the emergency department after a fall. Cost analysis was performed for cases in which the prescriptions exceeded the maximum recommended dose for this age group. RESULTS: A total of 40.6% of the prescriptions recorded were higher than the defined daily dose in older adults (DDDolderadults). Of the 57 patients who used BZD/Z drugs at higher-than-recommended doses, 53 experienced trauma and 33 required hospitalisation. The costs associated with emergency department services, tests performed and hospitalisation amounted to €1850/patient. CONCLUSIONS: Appropriate dosage of BZD/Z drugs in older adults could reduce both patient suffering and costs for the health system.

Prescripción de benzodiacepinas y caídas en mujeres y hombres ancianos / Benzodiazepine prescriptions and falls in older men and women

Objetivo. A pesar de las advertencias de numerosas asociaciones profesionales, las benzodiacepinas (BZD) y los hipnóticos Z (Z) son ampliamente prescritos a los ancianos ya que son especialmente susceptibles de padecer insomnio y ansiedad, pero a su vez resultan especialmente sensibles a la aparición de efectos secundarios a dichos medicamentos. En este estudio evaluamos la prescripción de BZD/Z en una muestra de ancianos (≥65) que se presentan en el servicio de urgencias de un hospital por haber sufrido una caída. Métodos. Recogimos información del tipo, número y dosis de los fármacos BZD/Z prescritos y exploramos la presencia de diferencias de género en dicha prescripción. Resultados. Las BZD/Z habían sido prescritas a un 43,6% de la muestra (n=654), más frecuentemente a las mujeres. El 78,4% de las prescripciones fueron de BZD/Z de vida media corta. La mayoría de los pacientes (83,5%) tomaban solamente un fármaco BZD/Z, pero un 16,5% consumían más de una BZD/Z, sin diferencias de género. Un 58% de los pacientes consumían dosis de BZD/Z más elevadas que las recomendadas para ancianos, siendo la proporción significativamente más elevada para los hombres (70% vs. 53,1%). Conclusiones. Alrededor de un 40% de los ancianos que acuden a un servicio de urgencias por haber sufrido una caída se encontraban tomando BZD/Z. Hemos hallado algunas diferencias de género en la prescripción de BZD/Z, especialmente en la prescripción por encima de la dosis recomendada para ancianos y de fármacos de vida media larga (AU)

Objective. Despite cautions by professional associations, benzodiazepines (BZD) and Z hypnotics (BZD/Z) are widely prescribed to older adults who are particularly susceptible to insomnia and anxiety, but who are also more sensitive to drugs adverse events. In this study, we assessed the prescription of BZD/Z drugs in a sample of older adults (≥65) who presented for emergency care after a fall. Methods. We collected the type, number and dose of BZD/Z drugs prescribed and explored gender differences in the prescription. Results. BZD/Z drugs were prescribed to 43.6% of the sample (n=654) and more frequently to women; 78.4% of prescriptions were for BZD/Z drugs with a short half-life. The majority of patients (83.5%) were prescribed only one type of BZD/Z, but 16.5% had been prescribed multiple BZD/Z drugs, with no gender difference. Doses higher than those recommended for older adults were prescribed to 58% of patients, being the doses significantly higher for men compared to women (70.0% vs 53.1%). Conclusions. Over 40% of older adults presenting for emergency care after a fall had previously been prescribed BZD/Z drugs. Some important gender differences in the prescription of BZD/Z drugs were seen, especially prescription above the recommended dose and of drugs with a long-half life (AU)

Benzodiazepine prescriptions and falls in older men and women. / Prescripción de benzodiacepinas y caídas en mujeres y hombres ancianos.

OBJECTIVE: Despite cautions by professional associations, benzodiazepines (BZD) and Z hypnotics (BZD/Z) are widely prescribed to older adults who are particularly susceptible to insomnia and anxiety, but who are also more sensitive to drugs adverse events. In this study, we assessed the prescription of BZD/Z drugs in a sample of older adults (≥65) who presented for emergency care after a fall. METHODS: We collected the type, number and dose of BZD/Z drugs prescribed and explored gender differences in the prescription. RESULTS: BZD/Z drugs were prescribed to 43.6% of the sample (n=654) and more frequently to women; 78.4% of prescriptions were for BZD/Z drugs with a short half-life. The majority of patients (83.5%) were prescribed only one type of BZD/Z, but 16.5% had been prescribed multiple BZD/Z drugs, with no gender difference. Doses higher than those recommended for older adults were prescribed to 58% of patients, being the doses significantly higher for men compared to women (70.0% vs 53.1%). CONCLUSIONS: Over 40% of older adults presenting for emergency care after a fall had previously been prescribed BZD/Z drugs. Some important gender differences in the prescription of BZD/Z drugs were seen, especially prescription above the recommended dose and of drugs with a long-half life.

Peripheral Inflammatory Parameters in Late-Life Depression: A Systematic Review.

Depressive disorders appear relatively frequently in older patients, and therefore represent an important disease burden worldwide. Given the high levels of inflammatory parameters found in depressed elderly patients, the "inflammaging" hypothesis is gaining strength. In this systematic review, we summarize current evidence regarding the relationship between inflammatory parameters and late-life depression, with a unique focus on longitudinal studies to guarantee temporality. According to the data summarized in this review, the levels of some proinflammatory parameters-especially interleukin (IL)-8, IL-6, and tumor necrosis factor (TNF)-α-could serve as biomarkers for the future development of depressive symptoms in elderly patients. Proinflammatory cytokines seem to be associated with the future development of clinically significant depression, irrespective of baseline scores, thus indicating that inflammation temporally precedes and increases depression risk. As insufficient research has been conducted in this field, further prospective studies are clearly warranted.