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1.  Enhanced Medical Rehabilitation increases therapy intensity and engagement and improves functional outcomes in post-acute rehabilitation of older adults: a randomized controlled trial 
For millions of disabled older adults each year, post-acute care in skilled nursing facilities (SNFs) is a brief window of opportunity to regain enough function to return home and live independently. Too often this goal is not achieved, possibly due to therapy that is inadequately intense or engaging. This study tested Enhanced Medical Rehabilitation, an intervention designed to increase patient engagement in, and intensity of, daily physical and occupational therapy sessions in post-acute care rehabilitation.
Randomized controlled trial of Enhanced Medical Rehabilitation versus standard-of-care rehabilitation.
Post-acute care unit of a skilled nursing facility in St Louis, MO.
26 older adults admitted from a hospital for post-acute rehabilitation.
Based on models of motivation and behavior change, Enhanced Medical Rehabilitation is a set of behavioral skills for physical and occupational therapists (PT/OT) that increase patient engagement and intensity, with the goal of improving functional outcome, through: (1) a patient-directed, interactive approach, (2) increased rehabilitation intensity, and (3) frequent feedback to patients on their effort and progress.
Therapy intensity: assessment of patient active time in therapy sessions. Therapy engagement: Rehabilitation Participation Scale. Functional and performance outcomes: Barthel Index, gait speed, and six-minute walk.
Participants randomized to Enhanced Medical Rehabilitation had higher intensity therapy and were more engaged in their rehabilitation sessions; they had more improvement in gait speed (improving from 0.08 to 0.38 meter/sec vs. 0.08 to 0.22 in standard of care,p=0.003) and six-minute walk (from 73 to 266 feet vs. 40 to 94 feet in standard of care, p=0.026), with a trend for better improvement of Barthel Index (+43 points vs. 26 points in standard of care, p=0.087), compared to participants randomized to standard-of-care rehabilitation.
Higher intensity and patient engagement in the post-acute rehabilitation setting is achievable, with resultant better functional outcomes for older adults. Findings should be confirmed in a larger randomized controlled trial.
PMCID: PMC3601780  PMID: 22863663
3.  Enhanced Medical Rehabilitation is feasible in a skilled nursing facility: preliminary data on a novel treatment for older adults with depression 
Archives francaises de pediatrie  1988;45(3):205-206.
PMCID: PMC3686856  PMID: 3395198
depression; elderly; rehabilitation; engagement; skilled nursing facility; occupational therapy; physical therapy; motivation; intensity; participation; disability; treatment
4.  Bringing the bedside to the bench, and then to the community: a prospectus for intervention research in late-life anxiety disorders 
Anxiety disorders are highly prevalent in elderly persons, and they are associated with functional impairment, poorer quality of life, and adverse long-term consequences such as cognitive decline. Intervention research in late-life anxiety disorders (LLAD) lags behind where it ought to be. Research in cognitive neuroscience, aging, and stress intersects in LLAD and provides the opportunity to develop innovative interventions to prevent chronic anxiety and its consequences in this age group.
This paper evaluates gaps in the evidence base for treatment of LLAD and synthesizes recent research in cognitive neuroscience, basic behavioral science, stress, and aging.
We examine three intervention issues in LLAD: (1) prevention; (2) acute treatment; and (3) pre-empting adverse consequences. We propose combining randomized controlled trials (RCTs) with mechanistic biobehavioral methodologies as an optimal approach for developing novel, optimized, and personalized treatments. Additionally, we examine three barriers in the field of LLAD research: (1) How do we measure anxiety?; (2) How do we raise awareness?; (3) How will we ensure our research is applicable to underserved populations (particularly minority groups)?
This prospectus outlines approaches for intervention research that can reduce the morbidity of LLAD.
PMCID: PMC3635100  PMID: 18613267
anxiety; generalized anxiety disorder; elderly; neurobiology; prevention; intervention; personalized medicine; stress; aging; fMRI
6.  Antidepressant Medication Augmented With Cognitive-Behavioral Therapy for Generalized Anxiety Disorder in Older Adults 
The American journal of psychiatry  2013;170(7):782-789.
Generalized anxiety disorder is common among older adults and leads to diminished health and cognitive functioning. Although antidepressant medications are efficacious, many elderly individuals require augmentation treatment. Furthermore, little is known about maintenance strategies for older people. The authors examined whether sequenced treatment combining pharmacotherapy and cognitive-behavioral therapy (CBT) boosts response and prevents relapse in older adults with generalized anxiety disorder.
Participants were individuals at least 60 years of age with generalized anxiety disorder (N=73) who were recruited from outpatient clinics at three sites. Participants received 12 weeks of open-label escitalopram and were then randomly assigned to one of four conditions:16 weeks of escitalopram (10–20 mg/day) plus modular CBT, followed by 28 weeks of maintenance escitalopram; escitalopram alone, followed by maintenance escitalopram; escitalopram plus CBT, followed by pill placebo; and escitalopram alone, followed by placebo.
Escitalopram augmented with CBT increased response rates on the Penn State Worry Questionnaire but not on the Hamilton Anxiety Rating Scale compared with escitalopram alone. Both escitalopram and CBT prevented relapse compared with placebo.
This study demonstrates effective strategies for treatment of generalized anxiety disorder in older adults. The sequence of antidepressant medication augmented with CBT leads to worry reduction in the short-term. Continued medication prevents relapse, but for many individuals, CBT would allow sustained remission without requiring long-term pharmacotherapy.
PMCID: PMC4090227  PMID: 23680817
7.  A High-Throughput Clinical Assay for Testing Drug Facilitation of Exposure Therapy 
Depression and anxiety  2013;30(7):631-637.
Several studies have demonstrated that D-cycloserine (DCS) facilitates exposure therapy. We developed a standardized test of this facilitation (i.e., a clinical assay), with the goal of testing for facilitation more quickly and inexpensively than a full clinical trial.
We developed a standardized brief exposure in which participants with social anxiety disorder gave a videotaped speech. Participants were randomized to receive a single capsule of 250mg DCS or a matching placebo prior to preparation for the speech. Distress levels were rated during the speech and again, approximately one week later, during a speech in an identical situation. Our primary measure of DCS’s exposure-facilitating effect was between-session habituation: whether or not the participants showed less distress during the second speech compared to the first. We also measured levels of subjective anxiety and fear of scrutiny.
Subjects randomized to receive DCS prior to their first speech were more likely to show between-session habituation than those who received placebo. We also found greater reduction of performance-related fear overall in the DCS group.
Our clinical assay was able to detect exposure facilitation effects rapidly and in a highly standardized way, and is estimated to take a fraction of the time and costs of a clinical trial. Given the increasing interest in using medications to enhance learning-based psychotherapy, this high-throughput clinical assay approach may be a favorable method for testing novel mechanisms of action, and clarifying optimal parameters, for therapy facilitation.
PMCID: PMC3699893  PMID: 23283838
D-cycloserine; exposure therapy; cognitive behavioral therapy; social anxiety; social anxiety disorder; social phobia; anxiety disorders
8.  Augmenting antidepressant medication with modular CBT for geriatric generalized anxiety disorder: a pilot study 
Generalized anxiety disorder (GAD) is a prevalent psychiatric condition in older adults with deleterious effects on health and cognition. Although selective serotonin reuptake inhibitor (SSRI) medications have some efficacy as acute treatments for geriatric GAD, incomplete response is the most common outcome of monotherapy. We therefore developed a novel sequential treatment strategy, using personalized, modular cognitive-behavioral therapy (mCBT) to augment SSRI medication.
In an open label pilot study (N =10), subjects received a sequenced trial of 12 weeks of escitalopram followed by 16 weeks of escitalopram augmented with mCBT. We also examined the maintenance effects of mCBT over a 28-week follow-up period following drug discontinuation and termination of psychotherapy.
Results suggest that (1) adding mCBT to escitalopram significantly reduced anxiety symptoms and pathological worry, resulting in full remission for most patients and (2) some patients maintained response after all treatments were withdrawn.
Findings suggest that mCBT may be an effective augmentation strategy when added to SSRI medication and provide limited support for the long-term benefit of mCBT after discontinuation of pharmacotherapy.
PMCID: PMC4070295  PMID: 20872925
aged; elderly; cognitive therapy; behavior therapy; drug therapy; psychotherapy; selective serotonin reuptake inhibitor
9.  Serotonin-norepinephrine reuptake inhibitor therapy in late-life depression is associated with increased marker of bone resorption 
Antidepressants have been associated with increased bone loss and fractures in older adults in observational studies, but the mechanism is unclear. We examined the effects of a serotonin-norepinephrine reuptake inhibitor, venlafaxine, on biomarkers of bone turnover in a prospective treatment study of late-life depression.
76 individuals aged 60 and older with current major depressive disorder received a 12-week course of venlafaxine XR 150-300mg daily. We measured serum C-terminal cross-linking telopeptide of type I collagen (β-CTX) and N-terminal propeptide of type I procollagen (P1NP), measures of bone resorption and formation, respectively, before and after treatment. We then analyzed the change in β-CTX and P1NP within each participant. Venlafaxine levels were measured at the end of the study. We assessed depression severity at baseline and remission status after treatment.
After 12 weeks of venlafaxine, β-CTX increased significantly, whereas P1NP did not significantly change. The increase in β-CTX was significant only in participants whose depression did not remit (increase of 10% in non-remitters versus 4% in remitters). Change in β-CTX was not correlated with serum levels of venlafaxine or norvenlafaxine.
Our findings suggest that the primary effect of serotonergic antidepressants is to increase bone resorption. However, such an increase in bone resorption seemed to depend on whether or not participants’ depression remitted. Our results are in agreement with prior observational studies reporting increased bone loss in older adults taking serotonergic antidepressants. These negative effects on bone homeostasis could potentially contribute to increased fracture risk in older adults.
PMCID: PMC4066460  PMID: 23358607
10.  Improving recognition of late life anxiety disorders in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition: observations and recommendations of the Advisory Committee to the Lifespan Disorders Work Group 
Recognition of the significance of anxiety disorders in older adults is growing. The revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM) provides a timely opportunity to consider potential improvements to diagnostic criteria for psychiatric disorders for use with older people. The authors of this paper comprise the Advisory Committee to the DSM5 Lifespan Disorders Work Group, the purpose of which was to generate informative responses from individuals with clinical and research expertise in the field of late-life anxiety disorders.
This paper reviews the unique features of anxiety in later life and synthesizes the work of the Advisory Committee.
Suggestions are offered for refining our understanding of the effects of aging on anxiety and other disorders (e.g., mood disorders) and changes to the DSM5 criteria and text that could facilitate more accurate recognition and diagnosis of anxiety disorders in older adults. Several of the recommendations are not limited to the study of anxiety but rather are applicable across the broader field of geriatric mental health.
DSM5 should provide guidelines for the thorough assessment of avoidance, excessiveness, and comorbid conditions (e.g., depression, medical illness, cognitive impairment) in anxious older adults.
PMCID: PMC4048716  PMID: 21773996
aging; anxiety; geriatric mental health; DSM-V; older adult; later life
11.  Association of Cortisol with Neuropsychological Assessment in Older Adults with Generalized Anxiety Disorder 
Aging & mental health  2013;17(4):432-440.
Older adults with Generalized Anxiety Disorder (GAD) have elevated diurnal cortisol patterns and show an increased cortisol stress response, which may increase risk for cognitive dysfunction. The current secondary data analysis examined how neuropsychological assessment as a possible laboratory stressor affects cortisol levels in late-life GAD and, in turn, how cortisol levels affect cognitive performance.
The current sample consisted of 69 individuals with late-life GAD and 39 psychiatrically-healthy group-matched comparison participants. Cognitive performance was measured with a neuropsychological battery and salivary cortisol was collected at several time points. Hierarchical regressions were performed to assess the moderating role of cortisol in the relationship between GAD status and cognitive performance.
The results revealed that older adults with GAD showed significantly lower cortisol levels during neuropsychological assessment, compared to their baseline levels. Further, there was a significant interaction between post-neuropsychological assessment cortisol levels and GAD status on several measures of cognitive performance. The interaction indicated that there is a significant negative relationship between cortisol level and cognitive performance in the GAD participants and no such relationship in the comparison participants.
Our results revealed that participating in a neuropsychological assessment was associated with reduced cortisol in GAD participants, suggesting that refocusing attention such as engaging in cognitive tasks had a cortisol-lowering effect. Further, a higher cortisol level appears to have a detrimental effect on cognitive performance for individuals with GAD but not psychiatrically-healthy comparison participants. The methodological and treatment implications of these findings are discussed.
PMCID: PMC3625449  PMID: 23336532
Generalized anxiety disorder (GAD); HPA axis; neuropsychological assessment; cortisol; stress
12.  Measuring Treatment Fidelity in a Rehabilitation Intervention Study 
Attaining and demonstrating treatment fidelity is critical in the development and testing of evidence-based interventions. Treatment fidelity refers to the extent to which an intervention was implemented in clinical testing as it was conceptualized and is clearly differentiable from control or standard-of-care interventions. In clinical research treatment fidelity is typically attained by intensive training and supervision techniques and demonstrated by measuring therapist adherence and competence to the protocol using external raters. Yet, in occupational therapy (OT) and physical therapy (PT) outcomes research, treatment fidelity methods have not been utilized, which in our view is a serious gap that impedes novel treatment development and testing in these rehabilitation fields. In this article we describe the development of methods to train and supervise therapists to attain adequate treatment fidelity in a treatment development project involving a novel OT and PT-based intervention. We also present a data-driven model for demonstrating therapist adherence and competence in the new treatment and its differentiation from standard-of-care. In doing so, we provide an approach that rehabilitation researchers can use to address treatment fidelity in OT and PT-based interventions. We recommend that all treatment researchers in rehabilitation disciplines use these or similar methods as a vital step in development and testing of evidence-based rehabilitation interventions.
PMCID: PMC3967862  PMID: 22377824
Treatment Fidelity; Research Design; Randomized Controlled Trial; Evidence-Based Treatment
13.  Escitalopram reduces attentional performance in anxious older adults with high-expression genetic variants at serotonin 2A and 1B receptors 
Older adults are among the most vulnerable to adverse cognitive effects of psychotropic medications and, therefore, the personalization of psychotropic treatment based on adverse drug reactions in this demographic is of great importance. We examined changes on neuropsychological tests of attention attributable to selective serotonin reuptake inhibitor (SSRI) treatment in anxious older adults. We also examined whether variation in serotonin receptor genes was associated with reduced attentional performance with SSRIs. We examined change from pre- to post-treatment in two attention measures – digit span and coding – in 133 adults aged ≥60 yr with generalized anxiety disorder in a 12-wk trial of escitalopram vs. placebo. We also examined attentional change in relation to genetic variability in four central serotonin receptors: the serotonin transporter and serotonin 1A, 2A and 1B receptors. Digit span scores were significantly lowered in patients receiving escitalopram relative to placebo, indicating reduced attentional performance attributable to the SSRI. Individuals with high-transcription variants in the receptors 5-HTR2A rs6311 and 5-HTR1B rs11568817 had greater reductions in attention with SSRI treatment compared to placebo. We conclude that SSRIs reduce attention in older adults, particularly in those with high-expression genetic variants at the serotonin 2A and 1B receptors. Analysing neuropsychological changes with SSRIs in relation to genetic variation in the serotonin system may be a useful strategy for detecting subgroups of older adults who are more susceptible to side-effects of SSRIs. These results, if confirmed, could lead to the personalization of SSRI use to reduce adverse neurocognitive effects.
PMCID: PMC3967864  PMID: 22717018
Anxiety; antidepressant; elderly; neuropsychological functioning; pharmacogenomics
15.  Escitalopram for Older Adults With Generalized Anxiety Disorder 
Generalized anxiety disorder (GAD) is one of the most common psychiatric disorders in older adults; however, few data exist to guide clinicians in efficacious and safe treatment. Selective serotonin reuptake inhibitors (SSRIs) are efficacious for younger adults with GAD, but benefits and risks may be different in older adults.
To examine the efficacy, safety, and tolerability of the SSRI escitalopram in older adults with GAD.
Design, Setting, and Participants
A randomized controlled trial in primary care practices and related specialty clinics in Pittsburgh, Pennsylvania, of 177 participants aged 60 years or older with a principal diagnosis of GAD randomized to receive either escitalopram or placebo and conducted between January 2005 and January 2008.
Twelve weeks of 10 to 20 mg/d of escitalopram (n=85) or matching placebo (n=92).
Main Outcome Measures
Cumulative response defined by Clinical Global Impressions-Improvement score of much or very much improved; time to response; and anxiety and role functioning changes measured by the Clinical Global Impressions-Improvement scale, Hamilton Anxiety Rating Scale, Penn State Worry Questionnaire, Late-Life Function and Disability Instrument activity limitations subscale, and the role-emotional impairment and social function subscales of the Medical Outcome Survey 36-item Short Form.
In the primary analytic strategy in which participants (n=33) were censored at the time of dropout, mean cumulative response rate for escitalopram was 69% (95% confidence interval [CI], 58%-80%) vs 51% (95% CI, 40%-62%) for placebo (P=.03). A conservative intention-to-treat analysis showed no difference in mean cumulative response rate between escitalopram and placebo (57%; 95% CI, 46%-67%; vs 45%; 95% CI, 35%-55%; P=.11). Participants treated with escitalopram showed greater improvement than with placebo in anxiety symptoms and role functioning (Clinical Global Impressions-Improvement scale: effect size, 0.93; 95% CI, 0.50-1.36; P<.001; Penn State Worry Questionnaire: 0.30; 95% CI, 0.23-0.48; P=.01; activity limitations: 0.32; 95% CI, 0.01-0.63; P=.04; and the role-emotional impairment and social function: 0.96; 95% CI, 0.03-1.90; P=.04). Adverse effects of escitalopram (P<.05 vs placebo) were fatigue or somnolence (35 patients [41.1%]), sleep disturbance (12 [14.1%]), and urinary symptoms (8 [9.4%]).
Older adults with GAD randomized to escitalopram had a higher cumulative response rate for improvement vs placebo over 12 weeks; however, response rates were not significantly different using an intention-to-treat analysis. Further study is required to assess efficacy and safety over longer treatment durations.
Trial Registration Identifier: NCT00105586
PMCID: PMC2840403  PMID: 19155456
16.  Memantine for late-life depression and apathy after a disabling medical event: a 12-week, double-blind placebo-controlled pilot study 
Preclinical data suggests that memantine, a noncompetitive glutamate N-methyl-D-aspartate (NMDA)-receptor blocker used for the treatment of moderate to severe Alzheimer’s disease, could reduce depressive and amotivated behavior occurring in the context of psychosocial stress. Therefore we examined whether memantine could reduce depressive symptoms and amotivation manifesting in older adults after a disabling medical event, thereby improving their functional recovery.
We recruited subjects aged 60 and older who had recently suffered a disabling medical event and were admitted to a skilled nursing facility for rehabilitation. Participants with significant depressive symptoms, defined as a Hamilton Rating Scale for Depression score of 10 or greater, and/or significant apathy symptoms, defined as an Apathy Evaluation Scale score of 40 or greater, were randomized to memantine (10mg/d for one week, then 10mg twice daily) or placebo, for 12 weeks. We also recruited participants without depressive or apathy symptoms for naturalistic follow-up as a non-depressed comparison group. Depressive and apathy symptoms were main outcomes; functional recovery, and self-report rating of helplessness, and onset of new depressive disorders were secondary outcomes.
Thirty-five older adults with significant depressive and/or apathy symptoms were randomized, of whom 27 (77.1%) completed the 12 week RCT. Both groups showed reduction in depressive symptoms (but no significant reduction in apathy symptoms) and improved function. However, there were no group differences between the memantine-randomized and placebo randomized participants on any outcome.
Memantine was not associated with superior affective or functional outcome compared to placebo in medically rehabilitating older adults with depressive and apathy symptoms.
PMCID: PMC3601891  PMID: 22173933
depression; elderly; rehabilitation; memantine; motivation; participation; disability; treatment
17.  An Open-Label Pilot Study of Acetylcholinesterase Inhibitors to Promote Functional Recovery in Elderly Cognitively Impaired Stroke Patients 
Impairments in cognition and motivationare common after stroke and predict poor functional recovery. Pharmacological agents that enhance cognition and/or diminish apathy may, when combined with traditional rehabilitative efforts, improve functional recovery. We investigated the feasibility of using acetylcholinesterase inhibitors in older patients with acute post-stroke cognitive impairment and examined their effects on functional recovery.
This 12-week open-label study prospectively treated ischemic stroke survivors aged ≥60 years who were undergoing inpatient rehabilitation and who had cognitive impairment in one or more domains (memory, attention or executive function). Participants received galantamine (maximum dose 24 mg/day) or donepezil (maximum dose 10 mg/day). Physical function was assessed using the Functional Independence Measure–motor subscale (FIM-motor); participants’ functional gains were compared to those of a matched historical comparator group. Changes in cognition and apathy were also assessed. Since donepezil and galantamine have different pharmacologic profiles, they were examined separately.
Forty participants started study medication; 14 participants terminated prematurely. Donepezil-treated participants experienced a 14-point greater improvement in the FIM-motor score compared to either galantamine-treated participants or the historical comparator group (repeated measures mixed model, group × time interaction p < 0.0001). Change in apathy, but not in cognition, was also associated with change in the FIM-motor score.
In this open-label study, participants receiving donepezil had better functional recovery than participants receiving galantamine or the historical comparators. This improvement may reflect efficacy at the starting dose for donepezil but not galantamine. A randomized trial is in progress.
PMCID: PMC2914451  PMID: 18667813
Cerebrovascular accident; Cholinesterase inhibitors; Rehabilitation, elderly; Cognition, stroke; Apathy, stroke
18.  Research to reduce the suicide rate among older adults: methodology roadblocks and promising paradigms 
The National Institute of Mental Health and the National Action Alliance for Suicide Prevention have requested input into the development of a national suicide research agenda. In response, a working group of the American Association for Geriatric Psychiatry has prepared recommendations to ensure that the suicide prevention dialogue includes older adults, a large and fast-growing population at high risk of suicide. In this Open Forum, the working group describes three methodology roadblocks to research into suicide prevention among elderly persons and three paradigms that might provide directions for future research into suicide prevention strategies for older adults.
PMCID: PMC3742079  PMID: 23728601
19.  Changes in neuropsychological functioning following treatment for late-life Generalized Anxiety Disorder 
Generalized Anxiety Disorder (GAD) in older adults is associated with neuropsychological impairment.
We examined neuropsychological functioning in older adults with GAD in comparison to psychiatrically healthy older adults and we examined changes during a 12-week, placebo controlled trial of escitalopram.
One hundred-sixty non-demented participants aged ≥60 with current GAD and 37 comparison subjects without psychiatric history underwent neuropsychological assessment. One hundred twenty-nine GAD participants were re-assessed post-treatment.
GAD participants performed worse than comparison subjects in information processing speed, working memory, inhibition, problem-solving (including concept formation and mental flexibility), and immediate and delayed memory. Neuropsychological functioning was correlated with everyday functioning. Low cognitive scorers experienced working memory, delayed memory and visuospatial ability improvement and those who reported clinical improvement in anxiety exhibited improvement in the ability to engage inhibition and episodic recall. These improvements were modest and of similar magnitude in both treatment conditions.
GAD in older adults is associated with neuropsychological impairments, which are associated with functional impairment. Those with GAD who either have low cognitive performance or report clinical improvement in anxiety post-treatment, show improvement in multiple cognitive domains. These findings underscore the importance of treatments that aid cognition as well as anxiety symptoms.
PMCID: PMC3633554  PMID: 21727232
generalized anxiety disorder; neuropsychological function
20.  Treating depression in older adults with dementia 
PMCID: PMC3632296  PMID: 21492102
21.  Anxiety – depression comorbidity – bête noire or quick fix? 
The common territory shared by anxiety and depression has always been a contentious subject. Research in favor of anxious depression as a potentially treatment-relevant subtype has been limited by diagnostic dilemmas and crude measurement. The most recent evidence from genetics, neuropeptide systems and functional neuroimaging suggests a valid diagnostic construct.
PMCID: PMC3619974  PMID: 22383763
22.  Predicting 6-week treatment response to escitalopram pharmacotherapy in late-life major depressive disorder 
Approximately half of older patients treated for major depressive disorder (MDD) do not achieve symptomatic remission and functional recovery with first-line pharmacotherapy. This study aims to characterize sociodemographic, clinical, and neuropsychologic correlates of full, partial, and non-response to escitalopram monotherapy of unipolar MDD in later life.
One hundred and seventy-five patients aged 60 and older were assessed at baseline on demographic variables, depression severity, hopelessness, anxiety, cognitive functioning, co-existing medical illness burden, social support, and quality of life (disability). Subjects received 10 mg/d of open-label escitalopram and were divided into full (n =55; 31%), partial (n =75; 42.9%), and non-responder (n =45; 25.7%) groups based on Hamilton depression scores at week 6. Univariate followed by multivariate analyses tested for differences between the three groups.
Non-responders to treatment were found to be more severely depressed and anxious at baseline than both full and partial responders, more disabled, and with lower self-esteem than full responders. In general partial responders resembled full responders more than they resembled non-responders. In multivariate models, more severe anxiety symptoms (both psychological and somatic) and lower self-esteem predicted worse response status at 6 weeks.
Among treatment-seeking elderly persons with MDD, higher anxiety symptoms and lower self-esteem predict poorer response after six weeks of escitalopram treatment.
PMCID: PMC3579589  PMID: 17486678
major depression; old age; escitalopram; treatment response
23.  Inflammatory Cytokine Levels and Depressive Symptoms in Older Women in the Year after Hip Fracture: Findings from the Baltimore Hip Studies 
Determine whether interleukin 6 (IL-6) or soluble tumor necrosis factor α receptor 1 (sTNF-αR1) are associated with depressive symptoms in the year after hip fracture
Prospective cohort
Three Baltimore-area hospitals
Community-dwelling women aged ≥65 years, admitted with a new, non-pathological fracture of the proximal femur (n=133).
At 2, 6 and 12 months postfracture, serum was analyzed for IL-6 and sTNF-αR1, and depressive symptoms were measured using the 15-item Geriatric Depression Scale (GDS). Generalized estimating equations were used to model the longitudinal relationship between IL-6 and sTNF-αR1 and GDS score. We also examined whether lower extremity function, as measured by Lower Extremity Gain Scale (LEGS), explained the relationship between IL-6, sTNF-αR1 and GDS score.
Patients in the highest categories of IL-6 (≥5.14 pg/ml) and sTNF-αR1 (≥2421 pg/ml) had the highest GDS scores in the year postfracture (p=0.09 for both). At 12 months postfracture, those in the highest IL-6 and sTNF-αR1 categories had GDS scores that were on average 1.9 (95% confidence interval [CI]: 0.4, 3.4; p=0.01) and 1.4 (95% CI: −0.1, 3.0; p=0.07) points higher than those in the lowest category, respectively. Adjusting for LEGS score, the mean difference in GDS scores for highest versus lowest IL-6 categories was 1.6 (95% CI: 0.2, 3.0; p=0.02) points at 12 months.
Results from these exploratory analyses support a role for inflammation in the pathophysiology of depressive symptoms after hip fracture. Depressive symptoms in the context of elevated cytokines may represent a sickness syndrome that is chronic in some individuals. Further research should establish the cause and effect of this relationship as well as long-term correlates.
PMCID: PMC3245645  PMID: 22188073
depressive symptoms; cytokines; hip fracture; Geriatric Depression Scale; elderly
24.  Elevated cortisol in older adults with Generalized Anxiety Disorder is reduced by treatment: a placebo-controlled evaluation of escitalopram 
Generalized Anxiety Disorder (GAD) is a common disorder in older adults which has been linked to hyperactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis in this age group. We examined whether treatment of GAD in older adults with a selective serotonin reuptake inhibitor (SSRI) corrects this HPA axis hyperactivity.
We examined adults aged 60 and above with GAD in a 12-week randomized controlled trial comparing the SSRI escitalopram to placebo. We collected salivary cortisol at six daily timepoints for two consecutive days to assess peak and total (area under the curve) cortisol, both at baseline and post-treatment.
Compared with placebo-treated subjects, SSRI-treated subjects had a significantly greater reduction in both peak and total cortisol. This reduction in cortisol was limited to subjects with elevated (above the median) baseline cortisol, in whom SSRI-treated subjects showed substantially greater reduction in cortisol than did placebo-treated subjects. Reductions in cortisol were associated with improvements in anxiety. Additionally, genetic variability at the serotonin transporter promoter predicted cortisol changes.
SSRI treatment of GAD in older adults reduces HPA axis hyperactivity. Further research should determine whether these treatment-attributable changes are sustained and beneficial.
PMCID: PMC3424606  PMID: 20808146
anxiety; cortisol; aging; health; stress; antidepressant
25.  The Burden of Late-Life Generalized Anxiety Disorder: Effects on Disability, Health-Related Quality of Life, and Healthcare Utilization 
To describe the burden of Generalized Anxiety Disorder (GAD), a common anxiety disorder in older adults.
Late-life depression and anxiety research clinic in Pittsburgh, PA.
One hundred sixty-four older adults with GAD and 42 healthy comparison participants with no lifetime history of psychiatric disorder were recruited from primary care and mental health settings as well as advertisements.
Participants were evaluated with the Late Life Function and Disability Index to assess disability, the MOS 36-Item Short Form Survey Instrument to assess health-related quality of life (HRQOL), and the Cornell Service Index to assess healthcare utilization.
Older adults with GAD were more disabled, had worse HRQOL, and had greater healthcare utilization, than nonanxious comparison participants, even in the absence of psychiatric comorbidity. After controlling for medical burden and depressive symptoms, higher severity of anxiety symptoms was associated with greater disability and poorer HRQOL in several domains. The greatest decrements in HRQOL and function were observed in measures assessing role functioning, including social function.
This study, the largest ever of GAD in older adults, provides evidence of the significant burden of this disorder in late life. Given the high prevalence and chronicity of GAD in the elderly, these data provide a public health imperative for finding and implementing effective management strategies for this typically undiagnosed and untreated disorder.
PMCID: PMC3408215  PMID: 19472438
Generalized anxiety disorder; older adults; health-related quality of life; disability; burden

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