Tanya J. Fabian

DHEA and DHEA‐S: A Review

Dehydroepiandrosterone (DHEA) and its sulfated metabolite DHEA‐S are endogenous hormones secreted by the adrenal cortex in response to adrenocorticotrophin (ACTH). Much has been published regarding potential effects on various systems. Despite the identification of DHEA and DHEA‐S more than 50 years ago, there is still considerable controversy as to their biological significance. This article reviews the metabolism and physiology of DHEA and DHEA‐S, the influence of age and gender on concentrations, and changes in endogenous concentrations associated with disease states and other factors, including diet and exercise. This article is unique in that it also summarizes the influence of drugs on DHEA and DHEA‐S concentrations, as well as concentrations of DHEA and DHEA‐S observed after the administration of DHEA by various routes. Sections of the article specifically address DHEA and DHEA‐S concentrations as they relate to stress, central nervous system function and psychiatric disorders, insulin sensitivity, immunological function, and cardiovascular disorders.

Endogenous concentrations of DHEA and DHEA-S decrease with remission of depression in older adults.

BACKGROUND Clinical studies of endogenous concentrations of dehydroepiandrosterone (DHEA) and its sulfated conjugate DHEA-S in depression are limited. This study was designed to evaluate the influence of successful pharmacological treatment of late-life depression on concentrations of DHEA, DHEA-S and cortisol. METHODS We determined endogenous concentrations of DHEA, DHEA-S and cortisol in elderly control subjects (n = 16) and in elderly depressed patients who remitted (n = 44) or failed to remit (n = 16) with pharmacological treatment. Depressed patients were treated for 12 weeks with either nortriptyline or paroxetine. RESULTS In remitters, DHEA and DHEA-S concentrations were lower at week 12 than at week 0 (p =.002 and p =.0001, respectively). In the nonremitters and control subjects, neither DHEA nor DHEA-S concentrations changed. Decreases in hormone concentrations were associated with improvement in mood and functioning in depressed patients. Although cortisol concentrations decreased in remitters and nonremitters, the change was not significant. CONCLUSIONS Our data suggest that the decrease in DHEA and DHEA-S in remitters is related to remission of depression rather than to a direct drug effect on steroids, as nonremitters had no change in hormone concentrations.

Influence of medications and diagnoses on fall risk in psychiatric inpatients

PURPOSE The influence of medications and diagnoses on fall risk in psychiatric inpatients was evaluated. METHODS In this retrospective case-control study, psychiatric inpatients age 18 years or older with a documented fall that was reported served as study cases. These patients were matched to control patients from the same hospital (1:1) by admission year, sex, and age. Psychiatric diagnoses evaluated included major depressive disorder, schizophrenia or schizoaffective disorder, bipolar disorder, Alzheimers disease and dementia, anxiety or neurosis, delirium, personality disorder, and obsessive-compulsive disorder. Medications assessed as independent variables were conventional antipsychotics, atypical antipsychotics, selective serotonin-reuptake inhibitors, tricyclic antidepressants, atypical antidepressants, monoamine oxidase inhibitors, lithium, anticonvulsants, benzodiazepines, nonbenzodiazepine sleep aids, Alzheimers disease medications, antihistamines, antiarrhythmics, antihypertensives, benign prostatic hyperplasia medications, oral hypoglycemic agents, histamine H(2)-receptor blockers, laxatives and stool softeners, muscle relaxants, nonsteroidal antiinflammatory drugs, opioids, Parkinsons disease medications, and overactive bladder medications. Univariate logistic regression models were developed for each risk factor to determine its impact on fall risk. RESULTS A total of 774 patient cases were matched with controls. Most falls occurred on the second day of hospitalization. Medications associated with a higher risk of falls were alpha-blockers, nonbenzodiazepine sleep aids, benzodiazepines, H(2)-blockers, lithium, antipsychotics, atypical antidepressants, anticonvulsants, and laxatives and stool softeners. Patients with a diagnosis of dementia and Alzheimers disease also had an increased risk of falling. CONCLUSION Alpha-blockers, nonbenzodiazepine sleep aids, benzodiazepines, H(2)-blockers, lithium, atypical antipsychotics, atypical antidepressants, anticonvulsants and mood stabilizers, conventional anti-psychotics, laxatives and stool softeners, and dementia and Alzheimers disease were significant predictors of inpatient falls in a psychiatric population.

Influence of DHEA administration on 24-hour cortisol concentrations.

DHEA is marketed and readily available as a daily nutritional supplement to counteract the effects of aging. The effect of DHEA administration on 24-hour plasma cortisol profiles has not been investigated. In this single-blind placebo-controlled crossover study, the effect of DHEA administration on cortisol concentrations was evaluated in healthy older women and men. Once each morning, subjects took either placebo (Days 1 to 7, and 23 to 29) or oral DHEA 200 mg (Days 8 to 22: doses 1 to 15). Twenty-four hour DHEA and cortisol concentrations were measured on Day 1 (placebo), Day 8 (DHEA dose 1), Day 15 (DHEA dose 8), Day 22 (DHEA dose 15), and Day 29 (placebo washout dose 7). DHEA administration resulted in a decrease in plasma cortisol concentrations (mean, peak, and/or AUC) in healthy older women and men. The cortisol-lowering effect of DHEA was more pronounced in women than in men in our study; pairwise differences in concentrations between days showed that relative to Day 1, cortisol was lower on Days 15, 22, and 29 in women (p = 0.0001) and on Day 15 in men (p = 0.002). The mechanism by which DHEA lowers plasma cortisol concentrations merits further investigation.

Paroxetine-Induced Hyponatremia in the Elderly due to the Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH)

This study investigated the development of hyponatremia and its underlying mechanism in elderly patients prescribed paroxetine. Patients were 15 men and women (mean age, 75.7 ± 5.3 years) who were participants in a treatment study of late-life depression and who were without medical illness or other medications known to cause hyponatremia or alter antidiuretic hormone (ADH) secretion. Blood samples for measurement of plasma sodium, ADH, blood urea nitrogen (BUN), creatinine, glucose, and osmolality were determined prior to initiation of paroxetine (week 0) and at 2, 4, 6, and 12 weeks of treatment with paroxetine. Hyponatremia (serum sodium < 135 mEq/L) was identified in 6 of 15 patients after 2 weeks of treatment with paroxetine. Despite low plasma osmolality, ADH levels were not suppressed appropriately. Data suggest hyponatremia is a common adverse event in elderly patients prescribed paroxetine and implicates inappropriate secretion of ADH as the potential mechanism. (J Geriatr Psychiatry Neurol 2003; 16:160-164).

Nicotine Replacement Prescribing Trends in a Large Psychiatric Hospital, Before and After Implementation of a Hospital-Wide Smoking Ban

OBJECTIVE We examined prescribing patterns for nicotine replacement therapies (NRTs) in a large psychiatric hospital, before and after the implementation of a smoking ban. METHOD We extracted 5 years of NRT utilization data from hospital pharmacy records. The ban went into effect on January 1, 2007. Data reflect NRT prescriptions from 2 years before and 3 years after the ban, and N = 30,908 total inpatient hospital admissions. RESULTS The monthly rate of total NRT prescriptions increased after the ban from M = 254.25 (SD = 126.60) doses per month to M = 4,467.52 (SD = 1,785.87) doses per month (>1,700% increase, p < .0001). After the smoking ban, clinicians prescribed higher doses of transdermal (but not oral) NRT (Tukey, p < .0001). Comparisons of NRT prescribing across hospital units tentatively suggested that patients being treated on the substance use disorders unit were prescribed more doses of NRT, as well as higher doses of NRT compared with patients on other units. Analysis of trends over time showed no apparent downward trend for NRT usage during the 3 years following the smoking ban, suggesting that clinicians continued to treat nicotine dependence after smoking was restricted. CONCLUSIONS Clinicians are more likely to identify and treat symptoms of nicotine withdrawal when smoking is restricted. Hospitals should consider monitoring prescriptions for NRT as part of their ongoing quality assurance practices so that patients receive aggressive treatment of nicotine withdrawal symptoms--an essential component of high-quality patient care.

Aripiprazole prescribing patterns and side effects in elderly psychiatric inpatients.

Objective This analysis examined dosing patterns and safety of aripiprazole in elderly inpatients. Methods A total of 52 elderly inpatients treated with aripiprazole over 3 years were retrospectively identified to examine dosing patterns and side effects associated with use of aripiprazole. Results The most common psychiatric diagnoses in these patients were schizophrenia/schizoaf-fective disorder (29%), bipolar disorder (25%), and major depressive disorder (23%). The median starting and maximum daily doses were 5 mg and 10 mg, respectively. For patients whose dose was titrated upward during the hospitalization, the mean time to the first titration was 3.4 days and the mean time to achieve maximum dose was 5 days. Nine patients (17%) had documented side effects, with agitation/activation the most frequently reported effect (8%). Aripiprazole was continued after hospital discharge in 54% of patients, with most patients receiving 10 to 15 mg/day. Conclusion Aripiprazole was generally well tolerated, with agitation/activation the most common side effect reported in elderly inpatients. (Journal of Psychiatric Practice 2009;15:150–153).

Decreasing pain and anxiety associated with patient-activated atrial shock: a placebo-controlled study of adjunctive sedation with oral triazolam.

Introduction: Implantable atrial defibrillators (IADs) have proved to be safe and effective in the management of atrial fibrillation. A potential limitation of self‐activated IAD therapy is patient‐reported pain and anxiety. The main objective of the present study was to determine whether triazolam improved patient perception of the shock experience or altered patient memory of shock discomfort relative to placebo.

An evaluation of inpatient treatment continuation and hospital readmission rates in patients with bipolar disorder treated with aripiprazole or quetiapine.

Objective. The primary objective of this study was to assess patient and treatment variables that have an impact on inpatient antipsychotic treatment continuation and 30-day hospital readmission rates in patients with bipolar disorder treated with aripiprazole or quetiapine. Methods. This was a retrospective cohort study of adult patients with bipolar disorder admitted to a psychiatric hospital. Patients who were initiated on aripiprazole or quetiapine during hospitalization were included in the analysis. The two groups were compared with regards to antipsychotic treatment continuation to discharge and 30-day hospital readmission rates using logistic regression analysis. Results. A total of 336 patients were included in the study. No difference in inpatient antipsychotic treatment continuation rates to discharge were observed, with 85.3% and 84.9% of patients in the aripiprazole and quetiapine cohorts, respectively, continuing treatment with the index antipsychotic to discharge (p = 0.92). Logistic regression analysis revealed that patients were more likely to be prescribed their index antipsychotic at discharge if they were younger than 40 years of age (OR = 2.05, 95% CI =1.08–3.89) and/or diagnosed with a bipolar depressed (OR = 3.05, 95% CI = 1.05–8.85) or mixed episode (OR = 4.14, 95% CI = 1.24–13.87) compared with a manic episode. Patients treated with divalproex (OR = 0.49, 95% CI = 0.25–0.94) or a benzodiazepine (OR = 0.37, 95% CI = 0.18–0.75) at discharge were less likely to be prescribed the index antipsychotic at discharge. Continuation of the index antipsychotic to discharge did not have an impact on readmission rates; admissions during the year before the index hospitalization were the only predictor of 30-day readmission rates (OR = 2.44, 95% CI = 1.08–5.48). Conclusion. No difference was observed in inpatient antipsychotic treatment continuation and 30-day hospital readmission rates in patients treated with either aripiprazole or quetiapine. (Journal of Psychiatric Practice 2013;19:288–295)

Improvement in functional outcomes with adjunctive aripiprazole versus placebo in major depressive disorder: a pooled post hoc analysis of 3 short-term studies.

OBJECTIVE To evaluate the effect of adjunctive aripiprazole to antidepressant therapy (ADT) on functional outcomes, as assessed by the Sheehan Disability Scale (SDS). METHOD A post hoc analysis of pooled data from 3 similarly designed randomized, placebo-controlled trials was conducted (CN138-139 [September 2004-December 2006], CN138-163 [June 2004-April 2006], and CN138-165 [March 2005-April 2008]). Patients with DSM-IV major depressive disorder who had a prior inadequate response to ADT received adjunctive aripiprazole or placebo to standard ADT. The change from baseline to endpoint on total SDS score and on individual SDS domains and the distributional categorical shifts of patient-reported severity of functional impairment on the SDS were assessed. RESULTS Aripiprazole compared to placebo augmentation produced significant improvements in self-reported functioning levels in the SDS mean total score (-1.2 vs -0.7, P ≤ .001) and social life (-1.4 vs -0.7, P ≤ .001) and family life (-1.4 vs -0.7, P ≤ .001) domains. Additionally, a significant number of patients exhibited a shift from a severe/moderate level of impairment at baseline to a mild level of functional impairment after 6 weeks of adjunctive aripiprazole treatment compared with placebo in the SDS mean total score (P = .001) and social life (P ≤ .001) and family life (P = .001) scores. CONCLUSIONS Aripiprazole augmentation of standard antidepressant therapy resulted in significant improvements in both total and individual domains of functioning, as assessed by the SDS, with significant categorical shifts from severe/moderate to mild levels of functioning compared with placebo augmentation. TRIAL REGISTRATION ClinicalTrials.gov identifiers: NCT00095823, NCT00095758, and NCT00105196.