Pharmacist-implemented intervention to surmount COVID-19 vaccination hesitancy in adults with substance use disorders.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Substance use disorders (SUDs) increase the risk and severity of infectious diseases, including coronavirus disease 2019 (COVID-19). Adults with a co-occurring SUD and psychiatric disorder were studied to elucidate the association between SUD severity and (1) COVID-19 vaccination status, (2) receptivity to a one-session intervention with a pharmacist advocating the benefits of vaccination, and (3) acceptance of referral for vaccination following the intervention. METHODS: COVID-19 vaccination status was recorded in 460 adults with SUD (324 males and 136 females) upon entry into inpatient treatment. A 2-parameter item response theory (IRT) model quantified SUD severity. Pharmacist-delivered intervention, modeled after the screening, brief intervention, and referral to treatment (SBIRT) protocol, was offered to unvaccinated participants. RESULTS: Higher SUD severity was associated with a lower vaccination rate. Nicotine, opioid, and sedative use disorders were most frequently associated with unvaccinated status. SUD severity was not associated with receptivity to intervention advocating vaccination or subsequent acceptance of a referral for vaccination. The portion of the sample that received the intervention was over 7 times more likely to accept a referral for vaccination when compared to participants who rejected the intervention (20.8% vs 2.8%). CONCLUSION: Pharmacist-administered intervention produced motivation for vaccination in a number of recipients; however, receptivity to the intervention was not related to SUD severity.

Geriatric Mental Healthcare Training: A Mini-Fellowship Approach to Interprofessional Assessment and Management of Geriatric Mental Health Issues.

INTRODUCTION: The population in United States aged 65 and older has rapidly grown and is projected to grow faster than any other segment of the population. Despite this demographic shift, the nation's geriatric workforce is shrinking. AIM: The primary goal of the fellowship was to form a learning collaborative that would help trainees in medicine, nursing, social work, pharmacy and occupational/physical therapy understand the roles of each discipline involved in the provision of geriatric mental healthcare and to enhance basic knowledge of common geriatric syndromes. METHODS: Faculty from the University of Pittsburgh developed a format for the mini-fellowship. Trainees from five disciplines were recruited for participation in the mini-fellowship. This was offered annually over four-year period, hosted by the John A. Hartford Foundation Centers of Excellence in Geriatric Psychiatry at the University of Pittsburgh and University of California at San Diego. RESULTS: Eighty-one participants across five schools of the health sciences completed the mini-fellowship. Feedback was positive: most participants appreciated learning from other team members, endorsed appreciation of the contributions of other disciplines to patient care, and reported improved understanding of three major geriatric syndromes. CONCLUSION: Conducting an interdisciplinary mini-fellowship in geriatric mental health was feasible and well received by trainees. The fellowship enabled better appreciation for the provision of geriatric mental health care within the context of an interprofessional team. However, decanal and faculty leadership across the schools needs to place greater emphasis on the importance of interprofessional team-based learning and to free up time for such activity.

Assessing need for pharmacist involvement to improve care coordination for patients on LAI antipsychotics transitioning from hospital to home: A work system approach.

BACKGROUND: The use of Long-Acting Injectable (LAI) antipsychotic medications has increased for patients with Serious Mental Illness (SMI). Care coordination for this population is complex, and pharmacist involvement may improve and support long-term medication adherence and patient outcomes. OBJECTIVES: (1) Examine pharmacists' role in addressing care coordination and adherence challenges for patients taking Long-Acting Injectable (LAI) antipsychotics; and (2) explore patients' medication use experiences with LAI antipsychotics and educational needs. METHODS: This project utilized a holistic work systems approach to assess the usefulness of implementing a pharmacist-led intervention to improve care coordination for patients taking LAI antipsychotics. Data collection and analyses were guided by the Systems Engineering Initiative for Patient Safety (SEIPS) model. Data were collected using interviews with healthcare team members and patients taking LAI antipsychotics and retrospective chart reviews at a psychiatric hospital in Southwestern Pennsylvania. Data collection elicited information about LAI care coordination, the pharmacist's role, and patients' experiences. Content and thematic analyses were conducted to identify opportunities to improve quality of care and patient outcomes. RESULTS: Sixteen healthcare team members and six patients were interviewed. Twenty patient charts were reviewed to examine the care coordination process. Four themes of the workflow process emerged: pharmacist consultation, in-hospital LAI administration, discharge planning, and outpatient treatment. Key challenges identified included inadequate communication, limited knowledge, and the need for standardized roles. Most patients did not know the name of their LAI antipsychotic and did not recall receiving medication counseling, but were interested in discussing medication concerns with pharmacists. CONCLUSIONS: There is a need for improved communication during LAI care coordination, targeted education for healthcare team members, and standardization of roles. Many patients did not have adequate LAI antipsychotic knowledge or receive appropriate medication counseling. Increased pharmacist involvement in the care coordination process may promote adherence and optimal management of SMI.

Second-Generation Antipsychotic Utilization and Metabolic Parameter Monitoring in an Inpatient Pediatric Population: A Retrospective Analysis.

BACKGROUND: Second-generation antipsychotics (SGAs) are prescribed for a variety of indications and are strongly associated with adverse metabolic effects. Studies of pediatric outpatients have revealed several deficiencies in monitoring practices for adverse effects associated with SGAs. OBJECTIVE: Our objective was to characterize SGA prescribing and metabolic parameter monitoring (MPM) in an inpatient pediatric population. METHODS: Patients aged <18 years and discharged on SGA treatment between 1 November 2013 and 30 April 2014 from an inpatient psychiatric institution in Pittsburgh, PA, USA were included. Electronic medical records (EMRs) were reviewed for patient age and weight and for parameters used by the International Diabetes Federation (IDF) to define metabolic syndrome: waist circumference, fasting blood glucose, triglycerides, high-density lipoprotein, and blood pressure. The primary outcome was the percent of patients with completed MPM, defined as all parameters being available within the patient's EMR in any form, except estimates. Secondary outcomes included percent of patients with existing metabolic syndrome or obesity according to IDF criteria, average total daily dose of individual SGAs, and frequency of individual SGA utilization. Data were analyzed utilizing univariate descriptive statistics. RESULTS: A total of 243 patients met inclusion criteria and were included in the analysis. For the primary outcome, 13.2% (n = 32) of patients had completed MPM for all parameters. Blood pressure was the most frequently documented parameter (n = 241; 99.2%), whereas waist circumference was the least (n = 67; 28%). Risperidone was the most commonly prescribed SGA (n = 99; 41%; average daily dose 1.92 mg). CONCLUSIONS: Compared with outpatient studies, rates of documented MPM for certain parameters (i.e., fasting blood glucose, lipids) is higher for pediatric inpatients treated with SGAs. However, several monitoring deficiencies are still noted.

Evaluation of Branched-Narrative Virtual Patients for Interprofessional Education of Psychiatry Residents.

OBJECTIVE: This pilot study evaluated the utility of branched-narrative virtual patients in an interprofessional education series for psychiatry residents. METHODS: Third-year psychiatry residents attended four interprofessional education advanced psychopharmacology sessions that involved completion of a branched-narrative virtual patient and a debriefing session with a psychiatric pharmacist. Pre- and post-assessments analyzed resident learning and were administered around each virtual patient. Simulation 4 served as a comprehensive review. The primary outcome was differences in pre- and post-assessment scores. Secondary outcomes included resident satisfaction with the virtual patient format and psychiatric pharmacist involvement. RESULTS: Post-test scores for simulations 1, 2, and 3 demonstrated significant improvement (p < 0.05) from pre-test scores. Scores for simulation 4 did not retain significance. Resident satisfaction with the branched-narrative virtual patient format and psychiatric pharmacist involvement was high throughout the series (100 %; n = 18). CONCLUSIONS: Although there are important methodological limitations to this study including a small sample size and absence of a comparator group, this pilot study supports the use of branched-narrative virtual patients in an interprofessional education series for advanced learners.

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.

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.

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.

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, Alzheimer's 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, Alzheimer's 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, Parkinson's 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 Alzheimer's 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 Alzheimer's disease were significant predictors of inpatient falls in a psychiatric population.

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/schizoaffective 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.

Best practices: an intervention to promote evidence-based prescribing at a large psychiatric hospital.

An intervention to affect prescribing behavior was implemented at a large psychiatric hospital. Articles providing support for appropriate dosing of quetiapine were distributed to physicians, and peer discussions about prescribing practices were held. From April 2005 through December 2006, low-dose quetiapine prescriptions (

Predictors of aripiprazole treatment continuation in hospitalized patients.

OBJECTIVE: Aripiprazole is a second-generation antipsychotic that is increasingly prescribed in a variety of psychiatric disorders. The goal of this study was to investigate patient and treatment factors associated with aripiprazole treatment continuation on hospital discharge in psychiatric inpatients. METHOD: This was a retrospective cohort analysis of patients admitted to a psychiatric hospital between January 1, 2003, and June 30, 2006, and treated with aripiprazole. The goal was to determine factors associated with continuation of aripiprazole throughout the hospital stay and on discharge from the hospital. Covariates assessed included patient demographics, prior psychiatric hospitalizations, diagnoses, prior antipsychotic use, and concomitant psychotropic medications. Aripiprazole-specific covariates were starting and maximum dose and dose titration pattern. Diagnoses were identified using ICD-9-CM codes. RESULTS: There were 1957 aripiprazole-treated patients included in this study, and 1573 (80%) continued aripiprazole treatment at the time of hospital discharge. Median starting doses were lower (5 mg/day) for younger and older patients, and patients with psychotic disorders received higher doses than other patients. Approximately 58% of patients had at least 1 aripiprazole dose titration while hospitalized, and most (73%) of those patients had a dose titration within 3 days of admission. Predictors of treatment continuation in this broad patient population were younger age, a diagnosis of bipolar or major depressive disorder, higher maximum aripiprazole doses, and upward dose titration within 3 days of admission. Patients receiving concomitant anticholinergics or antipsychotics were less likely to continue treatment as were those receiving aripiprazole at the time of hospitalization. CONCLUSION: In this acute inpatient psychiatric setting, continuation of aripiprazole treatment on discharge was achieved in most patients. Demographic, diagnostic, and treatment factors predicting aripiprazole treatment effectiveness were identified.

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. METHODS AND RESULTS: A total of 15 men and women (mean age: 59 +/- 6 years) were enrolled in this double-blind, placebo-controlled, crossover study of triazolam. Randomized study medication was administered orally 75 minutes prior to scheduled atrial shock delivery. Patient perception of the shock experience was assessed along with sedation, memory, anxiety, and mood. Triazolam reduced mean pre-shock anxiety (t= 2.98, df = 14, P = 0.01) and shock-related pain (t= 2.74, df = 13, P = 0.01) and intensity (t= 2.64, df = 13, P = 0.018) relative to placebo. Similarly, participants recalled less discomfort the morning after shock with triazolam than with placebo (t= 2.82, df = 11, P = 0.017). CONCLUSIONS: This study was the first to investigate the use of an oral benzodiazepine administered prior to patient-activated shock delivery with an IAD. Our data indicate that oral triazolam is beneficial in decreasing pain and anxiety associated with self-activated atrial defibrillation. If triazolam provides a similar benefit in the community to that which has been reported here, this medication could be offered to patients as an adjunct to intermittent IAD therapy.

Steroid sulfatase gene variation and DHEA responsiveness to resistance exercise in MERET.

Genetic influences and endurance exercise have been shown to alter circulating concentrations of dehydroepiandrosterone (DHEA) and its sulfated conjugate, DHEAS. We hypothesized that acute resistance exercise (RE) and training (RET) would increase DHEA steroids, and the magnitude of the increase would be influenced by a steroid sulfatase (STS) gene variation. Fasting blood samples were collected before and after the first (S1) and last (S30) session of a 10-wk RET program in 62 men and 58 women [age: 21.0 yr (2.4)]. Acute RE increased both DHEA [+2.8 (0.4), S1; +1.6 ng/ml (0.4), S30; P < 0.001] and DHEAS [+154 (24), S1; +166 ng/ml (15), S30; P < 0.001] and decreased DHEAS:DHEA [-27 (8), S1; -15 (7), S30; P < 0.01]. RET reduced resting DHEAS (-122 ng/ml, P < 0.01) and decreased DHEA response to RE (-50%, P < 0.05). Subjects with an STS "G" allele (n = 36) had greater acute changes in DHEA [+4.4 (0.7) vs. +2.0 ng/ml (0.5), S1; +3.2 (0.6) vs. +1.0 ng/ml (0.4), S30; P < 0.01] and DHEAS:DHEA [-37 (11) vs. 5 (7), S30, P < 0.05] than those subjects with only an "A" allele (n = 84). The observed increase in DHEA and DHEAS and decrease in DHEAS:DHEA suggest RE-induced STS activation which is influenced by the STS polymorphism.

Paroxetine-induced hyponatremia in older adults: a 12-week prospective study.

BACKGROUND: Older depressed patients are at high risk for development of hyponatremia after initiation of the selective serotonin reuptake inhibitor paroxetine, despite clinical monitoring and preventive management. The purposes of this study were to determine the incidence and etiology of paroxetine-induced hyponatremia in older patients and to identify patient characteristics that may account for variability in susceptibility to this adverse event. METHODS: This prospective, longitudinal study was conducted in a university-based ambulatory psychiatric research clinic from August 1999 through September 2001. Patients included 75 men and women aged 63 through 90 years (mean +/- SD age, 75.3 +/- 6.0 years) who received a diagnosis of a current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, major depressive episode and were prescribed paroxetine. We monitored plasma sodium levels before initiating paroxetine therapy and after 1, 2, 4, 6, and 12 weeks of treatment. In a subset of individuals, we measured levels of antidiuretic hormone, glucose, serum urea nitrogen, and creatinine. Hyponatremia was defined as a plasma sodium level of less than 135 mEq/L after initiation of paroxetine therapy. RESULTS: Hyponatremia developed in 9 (12%) of the 75 patients after initiation of paroxetine treatment. Mean +/- SD time to development of hyponatremia was 9.3 +/- 4.7 days (median, 9 days; range, 1-14 days; n = 8). In the multivariate regression, lower body mass index and lower baseline plasma sodium level (<138 mEq/L) were significant risk factors for the development of hyponatremia in these patients. CONCLUSIONS: Hyponatremia is an under recognized and potentially serious complication of paroxetine treatment in older patients. Our results provide a foundation for understanding the etiology and risk factors associated with paroxetine-induced hyponatremia.

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.

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.