SUMMARY

Objective

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.

Methods

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.

Results

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.

Conclusion

Among treatment-seeking elderly persons with MDD, higher anxiety symptoms and lower self-esteem predict poorer response after six weeks of escitalopram treatment.

OBJECTIVES

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

DESIGN

Prospective cohort

SETTING

Three Baltimore-area hospitals

PARTICIPANTS

Community-dwelling women aged ≥65 years, admitted with a new, non-pathological fracture of the proximal femur (n=133).

MEASUREMENTS

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.

RESULTS

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.

CONCLUSION

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.

Background

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.

Methods

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.

Results

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.

Conclusions

SSRI treatment of GAD in older adults reduces HPA axis hyperactivity. Further research should determine whether these treatment-attributable changes are sustained and beneficial.

Objective

To describe the burden of Generalized Anxiety Disorder (GAD), a common anxiety disorder in older adults.

Design

Cross-sectional.

Setting

Late-life depression and anxiety research clinic in Pittsburgh, PA.

Participants

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.

Measurements

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.

Results

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.

Conclusion

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.

Objective

Generalized Anxiety Disorder (GAD) is common in older adults and can be treated with SSRIs. Genetic variation in the serotonin transporter gene promoter region is posited to be associated with SSRI efficacy: two polymorphisms (5HTTLPR s/l and rs25531 g/a) form a haplotype with the La combination having higher transcription activity than other haplotypes. We hypothesized that GAD patients with no La haplotypes (La-) have lower SSRI treatment efficacy than those with 1-2 La haplotypes (La+).

Method

The study enrolled subjects aged 60 and older with a principal diagnosis of GAD, into a twelve-week, randomized trial of escitalopram vs. placebo. One hundred-fifty subjects were genotyped for the serotonin transporter promoter region haplotype and were divided into La- and La+ genotype groups; the primary analyses were done in European-Americans only (N=125; 59 escitalopram and 66 placebo).

Results

Escitalopram had no efficacy in the La- group versus moderate efficacy in the La+ group. This genetic moderation of SSRI efficacy was due to a higher placebo response in La- subjects, compared to La+ subjects. Drug concentration did not affect the genetic results. Exploratory analyses suggest that La- subjects had greater variability of anxiety symptoms unrelated to treatment.

Conclusions

The serotonin transporter promoter haplotype is associated with variability in SSRI efficacy for late-life GAD. The variability may result from a genetic effect on anxiety symptom variability unrelated to treatment, rather than a pharmacodynamic effect that has been previously assumed. Further research is needed to understand the pharmacogenetic mechanism of this haplotype.

Neurodevelopmental changes over the lifespan, from childhood through adulthood into old age, have important implications for the onset, presentation, course, and treatment of anxiety disorders. This article presents data on anxiety disorders as they appear in older adults, as compared with earlier in life. In this article, we focus on aging-related changes in the epidemiology, presentation, and treatment of anxiety disorders. Also, this article describes some of the gaps and limitations in our understanding and suggests research directions that may elucidate the mechanisms of anxiety disorder development later in life. Finally we describe optimal management of anxiety disorders across the lifespan, in “eight simple steps” for practitioners.

Context

Cognitive impairment in late-life depression is a core feature of the illness.

Objective

to test whether donepezil + antidepressant is superior to placebo + antidepressant in (1) improving cognitive performance and instrumental activities of daily living and (2) reducing recurrences of depression over two years of maintenance treatment.

Design

Randomized, double-blind, placebo controlled maintenance trial.

Setting

university clinic

Main Outcome Measures

global neuropsychological performance, cognitive instrumental ADL, and recurrent depression.

Results

Donepezil + antidepressant temporarily improved global cognition (treatment by time interaction F = 3.78, df = 2, 126, p = .03), but effect sizes were small (Cohen’s d = 0.27: group difference at 1 year). A marginal benefit to cognitive instrumental ADL was also observed (treatment by time interaction; F = 2.94; df = 2, 137, p = 0.06). The donepezil group was more likely to experience recurrent major depression: 35% [95% CI: 24%, 46%] versus 19% [95% CI: 9%, 29%] (log rank chi squared = 3.97, p = .05); hazard ratio = 2.09 [95% CI: 1.00, 4.41]. Post-hoc subgroup analyses showed that, of 57 participants with mild cognitive impairment, 3/30 on donepezil (10%; 95% CI: 0, 21%) and 9/27 on placebo (33%; 95% CI: 16%, 51%) converted to dementia over two years (Fisher exact p = 0.05). The MCI subgroup had a 44 percent recurrence rate of major depression on donepezil verses 12% on placebo (LR=4.91, p=.03). The subgroup with normal cognition (n = 73) showed no benefit on donepezil or increase in recurrence of major depression.

Conclusion

Whether ChEI should be used as augmentation in the maintenance treatment of late-life depression depends upon a careful weighing of risks and benefits in those with MCI. In cognitively intact patients, donepezil appears to have no clear benefit for preventing progression to MCI/dementia or recurrence of depression.

Objective

To examine associations between cognitive and affective impairments and rehabilitation participation during stroke rehabilitation.

Design

Secondary analyses of stroke patients who received acetylcholinesterase inhibitors during inpatient rehabilitation.

Setting

University-affiliated inpatient rehabilitation facilities.

Patients

Individuals admitted to inpatient stroke rehabilitation with impairment in attention, memory or executive functions (N=44).

Interventions

Secondary analysis of individuals receiving inpatient stroke rehabilitation care plus random assignment to one of two acetylcholinesterase inhibitors or no drug at rehabilitation admission.

Main Outcome Measure(s)

Correlations between measures of cognitive (Digit Span, Hopkins Verbal Learning Test, and Executive Interview) and affective impairments (Hamilton Rating Scale for Depression and Apathy Evaluation Scale) and participation (Pittsburgh Rehabilitation and Participation Scale) were examined. Significant correlates of participation were examined in a linear multiple regression model.

Results

Executive functions and depressive symptoms were significant correlates of participation. After controlling for baseline disability, executive functions predicted participation, but depressive symptoms did not, F4,32=9.35; R2=.54, P<.001.

Conclusions

These findings are an important first step toward understanding potentially modifiable clinical factors that contribute to rehabilitation participation, and overall functional status after rehabilitation. A better understanding of cognitive impairment and rehabilitation participation may be used to develop strategies for improving functional outcomes after stroke.

Objective and Methods

The neurobiology of late-life anxious depression (LLAD) is poorly characterized despite evidence that this is a common and severe subtype of late-life depression. To identify the neuroanatomical substrate of late-life anxious depression, we examined event-related fMRI data collected in 8 subjects with late-life depression, half of whom had high levels of comorbid anxiety. Subjects were trained on the Preparing to Overcome Prepotency (POP) task, which is an executive control task that reliably activates the lateral prefrontal cortex - anterior cingulate cortex cognitive control circuit.

Results

Time series analysis showed that, when compared with elderly depressed subjects, elderly subjects with anxious depression performing the POP task produced a significantly greater and more sustained signal in three regions: BA 24 (dorsal anterior cingulate), BA31 (posterior cingulate) and BA6 (prefrontal cortex). While elderly subjects with pure depression presented a bimodal activation curve in the dorsal anterior cingulate and the posterior cingulate, elderly subjects with anxious depression presented a sustained unimodal activation pattern.

Conclusions

Our preliminary results suggest specific activation patterns unique to anxious depression that may suggest greater and more sustained efforts of the ACC to carry out cognitive control tasks. Further research is needed to clarify the neuroanatomical basis of late-life anxious depression.

The authors examined apathy symptoms, their improvement, and their association with functional recovery, after a hip fracture. Of 126 subjects, 37% had clinically significant apathy symptoms, which predicted functional outcome (i.e., poorer recovery from the fracture among those with higher baseline apathy). Of subjects with baseline high apathy, approximately one-third improved; these subjects had a better functional outcome than those with persistently high apathy scores. It is concluded that apathy symptoms are common post-hip fracture but improve in one-third of individuals, with a concomitant improved recovery. Interventions to prevent or improve apathy in elderly persons deserve further attention.

Objective

To determine the feasibility and safety of aripiprazole augmentation for incomplete response to sequential SSRI and SNRI pharmacotherapy in late-life depression.

Method

This study was a 12-week open-label pilot study of 24 patients aged 65 and above (mean age 73.9) diagnosed with MDD who responded partially (Hamilton Rating Scale for Depression [HRSD, 17-item] score of 11–15) or not at all (HRSD >15) to a 16-week trial of escitalopram, followed by either duloxetine (up to 120 mg/d for 12 weeks) or venlafaxine (up to 225 mg/d for 12 weeks). Subjects received 2.5–15 mg/day of adjunctive aripiprazole (average dose 9.0 mg) for 12 weeks. The criterion for remission during treatment with aripiprazole was HRSD ≤ 10 for 2 consecutive weeks.

Results

Of 24 subjects in the intent to treat study group, 19 completed 12 weeks of augmentation with aripiprazole, 12/24 (50%) met criteria for remission, and 2/24 discontinued due to side effects (sedation, akathisia). The mean HRSD score decreased significantly by 6.4 (5.8) points (paired t-test for means, p<0.01, df=16). There were no relapses among the 12 subjects who participated in continuation treatment over a median period of 27.6 weeks.

Conclusions

In older adults with MDD with incomplete response to SSRI and SNRI pharmacotherapy, aripiprazole was well tolerated, and symptoms of depression improved significantly during treatment with aripiprazole. A randomized double-blind, placebo-controlled trial of adjunctive aripiprazole for incomplete response in late-life depression is warranted, to further evaluate benefit and risk.

Background

Up to 50% of depressed older adults either do not adequately respond to or are unable to tolerate treatment with a serotonin-specific reuptake inhibitor. On the basis of previous experience with serotonin-norepinephrine reuptake inhibitors, we predicted at least a 50% response rate to open-label treatment with duloxetine in subjects who were resistant to treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram.

Method

Community-dwelling subjects aged 65 years or older with current nonpsychotic major depressive disorder as established by the Structured Clinical Interview for DSM-IV received escitalopram under protocolized conditions between April 2004 and September 2006. Subjects who failed to meet response criteria or relapsed after achieving an initial response were subsequently switched to open treatment with duloxetine up to 120 mg/day. Side effects were assessed at every visit.

Results

Subjects (N = 40) switched to duloxetine had a mean (SD) age of 74.4 (7.0) years and a baseline (before escitalopram) 17-item Hamilton Rating Scale for Depression (HAM-D-17) score of 20.0 (3.5) and were predominantly female (65.0%) and white (82.5%). The mean (SD) maximum dose of duloxetine was 93.0 (27.8) mg/day. Subjects received this maximum dose for a median duration of 6.9 weeks. Fifty percent of subjects (N = 20) met criteria for full response, 17.5% (N = 7) were partial responders, and 32.5% (N = 13) did not respond. The median time to response was 12.0 weeks (95% CI = 8.4 to 14.6). Five of the subjects (12.5%) discontinued duloxetine because of intolerable side effects.

Discussion

These open-label data suggest that duloxetine at doses up to 120 mg/day is a well-tolerated and potentially effective treatment for older adults who fail to respond to an adequate trial of an SSRI. These results are preliminary, and future controlled studies are required to test the efficacy of rescue pharmacotherapy with duloxetine.

Trial Registration

clinicaltrials.gov Identifier: NCT00177671

Context

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.

Objective

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.

Interventions

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.

Results

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%]).

Conclusions

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

clinicaltrials.gov Identifier: NCT00105586

Objectives

The Generalized Anxiety Disorder Severity Scale (GADSS) is a validated measure of Generalized Anxiety Disorder symptom severity. Given the high prevalence of Generalized Anxiety Disorder (GAD) in the elderly and the need for a validated scale to assess GAD severity in this age group, we examined the psychometric properties of the GADSS in the elderly.

Design, Setting, Participants

We examined a sample of 134 elderly subjects (age 60 and above) who met diagnostic criteria for current GAD, 33 healthy elderly comparison subjects (age 60 and above) and 186 younger subjects (age 18 to 60) diagnosed with GAD.

Results

The GADSS had a high internal consistency in the elderly subjects (raw Cronbach’s alpha =0.76). Pearson correlations showed a significant positive correlation between GADSS, Hamilton Rating Scale for Anxiety and Penn State Worry Questionnaire. Pearson correlations showed an inverse significant correlation between GADSS and the Medical Outcome Study SF-36. There was no correlation between GADSS and Mini Mental State Examination or Cumulative Illness Rating Scale for Geriatrics.

Conclusions

The results showed a good convergent, concurrent and discriminant validity of the GADSS when used for elderly with GAD. We conclude that GADSS is a valid measure of GAD symptom severity in older adults.

Background

Comorbid anxiety symptoms are common in late-life depression (LLD) and predict poorer treatment outcomes. No research has delineated the impact of different dimensions of anxiety (such as worry/anxious apprehension and panic/anxious arousal) on treatment response in LLD. We explored the impact of the dimensions of worry and panic on acute and maintenance treatment outcomes in LLD.

Methods

We measured anxiety symptoms in 170 LLD subjects receiving protocolized treatment. Exploratory principal components analysis was used to delineate dimensions of anxiety symptoms. We defined sub-groups based on factor scores. We used survival analysis to test the association of pre-treatment anxiety dimensions with time to response and time to recurrence of LLD.

Results

The principal component analysis found two factors: “worry” and “panic”. Three sub-groups were defined: low panic-low worry, low panic-high worry, and high panic-high worry. The low panic-high worry and high panic-high worry sub-groups had longer time to response than the low panic-low worry sub-group. Time to recurrence was longer in low panic-low worry subjects randomized to drug. Among subjects with high worry, there was no difference between those with low versus high panic regarding both time to response and time to recurrence of LLD.

Conclusion

High levels of worry were associated with longer time to response and earlier recurrence with pharmacotherapy for LLD. There was no additional effect of panic symptoms on treatment outcomes when accounting for the effects of excessive worry. These results suggest that worry symptoms should be a focus of strategies to improve acute and maintenance treatment response in LLD.

Background

Depression is common after hip fracture and is associated with poorer functional recovery. Polymorphisms of the serotonin 1a (5HTR1A) and 2a receptors (5HTR2A) are associated with depression; therefore, we examined their association with depressive symptoms and functional recovery after hip fracture.

Methods

145 elderly women were followed for 12 months after hip fracture. Depressive symptoms were measured with the 15-item Geriatric Depression Scale (GDS). Functional status was measured by Lower Extremity Physical and Instrumental Activity of Daily Living scales (LPADLs and IADLs). Time-adjusted general linear regression models compared mean GDS between those with and without risk alleles for 5HTR1A and 5HTR2A.

Results

Women with 1–2 copies of the 5HTR1A (−1019) G allele had higher GDS scores (Adjusted Mean Difference=0.59; 95% CI, 0.12–1.06), and poorer IADL scores (Adjusted Mean Difference=0.24; 95%CI −0.002–0.49), compared to those without this allele, controlling for potential confounders and 5HTR2A. Depressive symptoms partly accounted for poorer IADL recovery. Women with 1–2 copies of the 5HTR2A (−1438) C allele did not have significantly higher GDS scores (Adjusted Mean Difference=0.34; 95%CI, −0.20–0.87) and had better IADL scores (Adjusted Mean Difference=−0.40; 95%CI −0.74--0.06) than those with A/A genotype.

Limitations

The findings are limited by small sample size and the use of a screening scale to measure depression.

Conclusions

The 5HTR1A (−1019) G allele is associated with increased depressive symptoms after hip fracture, which in turn accounts for poorer functional recovery. These results suggest a role for serotonergic genetic variation in elderly persons’ resilience and recovery from medical events.

Summary

Age-associated alterations in hypothalamic–pituitary–adrenal (HPA) axis functioning may make individuals more susceptible to HPA dysregulation in the context of mood and anxiety disorders. Little to no research has been done to examine HPA axis function in generalized anxiety disorder (GAD), particularly in late-life GAD, the most prevalent anxiety disorder in the elderly. The study sample consisted of 71 GAD subjects and 40 nonanxious comparison subjects over 60 years of age. We examined the hypotheses that elderly individuals with GAD will have elevated salivary cortisol levels compared to nonanxious subjects, and that elevated cortisol levels in GAD will be associated with measures of symptom severity. We report that late-life GAD is characterized by elevated basal salivary cortisol levels, with higher peak cortisol levels and larger areas under the curve, compared to nonanxious subjects. Additionally, severity of GAD as measured by the GAD Severity Scale and the Penn State Worry Questionnaire are positively correlated with cortisol levels. These data demonstrate HPA axis dysfunction in late-life GAD and suggest the need for additional research on the influence of aging on HPA axis function in mood and anxiety disorders.

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Background

The Generalized Anxiety Disorder Severity Scale (GADSS) is an interview rating scale designed specifically for assessing symptom severity of generalized anxiety disorder (GAD), which has demonstrated positive psychometric data in a sample of adult primary care patients with GAD and panic disorder. However, the psychometric properties of the GADSS have not been evaluated for older adults.

Methods

This study evaluated the psychometric properties of the GADSS, administered via telephone, with a sample of older primary care patients (n = 223) referred for treatment of worry and/or anxiety.

Results

The GADSS demonstrated adequate internal consistency, strong inter-rater reliability, adequate convergent validity, poor diagnostic accuracy, and mixed discriminant validity.

Conclusions

Results provide mixed preliminary support for use of the GADSS with older adults. Depression and Anxiety 26:E10–E15, 2009.

Background

Many older patients who recover from an episode of major depression continue to suffer from depressed mood, anxiety, and sleep problems. Our study assesses the impact of these residual symptoms on the risk of recurrence during maintenance treatment of late-life depression.

Method

We analyzed data from a randomized clinical trial of maintenance treatment in patients with unipolar depression aged ≥70, 116 of whom remitted and remained stable during open pharmacotherapy and interpersonal psychotherapy (IPT) and were randomized to clinical management/pharmacotherapy; clinical management/placebo; monthly maintenance IPT/pharmacotherapy; or monthly maintenance IPT/placebo. We assessed the impact of overall residual symptoms (based on the Hamilton Depression Rating Scale (HAM-D) total score) and of specific residual symptom clusters – mood symptoms (depressed mood, guilt, suicidality, energy/interests), sleep disturbance (early, middle, late insomnia), and anxiety (agitation, psychic and somatic anxiety, hypochondriasis) measured at randomization. Sleep disturbance was also assessed with the Pittsburgh Sleep Quality Index (PSQI). We used Cox proportional hazards regression models controlling for antidepressant medication versus placebo to identify predictors of recurrence.

Results

Residual anxiety and residual sleep disturbance (as measured by the PSQI but not the HAM-D) independently predicted early recurrence.

Limitations

Use of HAM-D clusters to define residual symptoms; analysis limited to completers of acute and continuation treatment.

Conclusions

In patients with late-life depression who have remitted with pharmacotherapy and psychotherapy, the deleterious effect of residual symptoms is due to persisting anxiety and, possibly, residual sleep disturbance.

Incomplete response in the treatmen tof late-life depression is a large public health challenge: at least 50% of older people fail to respond adequately to first-line antidepressant pharmacotherapy, even under optimal treatment conditions. Treatment-resistant late-life depression (TRLLD) increases risk for early relapse, undermines adherence to treatment for coexisting medical disorders, amplifies disability and cognitive impairment, imposes greater burden on family caregivers, and increases the risk for early mortality, including suicide, Gettinq to and sustaininq remission is the primary goal of treatment yet there is a paucity of empirical data on how best to manage TRLLD. A pilot study by our group on aripiprazole augmentation in 24 incomplete responders to sequential SSRI and SRNI pharmacotherapy found that 50% remitted over 12 weeks with the addition of aripiprazole, and that remission was sustained in all participants during 6 months of continuation treatment In addition to controlled assessment, evidence is needed to support personalized treatment by testing the moderating role of clinical (eg, comorbid anxiety, medical burden, and executive impairment) and genetic (eg, selected polymorphisms in serotonin, norepinephrine, and dopamine genes) variables, while also controlling for variability in drug exposure. Such studies may advance us toward the goal of personalized treatment in late-life depression.

Objective

Depression, apathy (amotivation), and cognitive impairment are common comorbidities in hip fracture patients, which may adversely affect functional outcome of rehabilitation. We examined whether post-fracture measures of mood, motivation, or cognition are associated with rehabilitation outcome (defined as functional improvement) in inpatient rehabilitation facilities (IRFs), as compared to skilled nursing facilities (SNFs).

Methods

This prospective study examined elderly patients who received surgical fixation for hip fracture and then received post-acute rehabilitation at an IRF or a SNF. Subjects were characterized at baseline for depression using the Hamilton Rating Scale for Depression, apathy/amotivation using the Apathy Evaluation Scale, and mild-moderate cognitive impairment using the Mini-Mental Status Examination. Functional recovery was measured over 12-week follow-up using the Functional Independence Measure.

Results

58 subjects were discharged from acute care to an IRF and 39 to a SNF. Patients with depression, apathy, or cognitive impairment who received rehabilitation at an IRF had significantly better functional outcomes than similarly-impaired patients at SNFs, and similar outcomes as nondepressed, motivated, and cognitively intact elderly at IRFs.

Conclusion

These findings suggest that depression, amotivation, or mild-moderate cognitive impairment after hip fracture do not reduce the benefit of post-acute rehabilitation in an IRF.

OBJECTIVE

To determine the number of physician office visits by adults in which an anxiety disorder diagnosis was recorded and rates of treatment during these visits.

DESIGN

We used data from the 1985, 1993, 1994, 1997, and 1998 National Ambulatory Medical Care Surveys, which is a nationally representative series of surveys of office-based practice employing clustered sampling.

SETTING

Office-based physician practices in the United States.

PARTICIPANTS

A systematically sampled group of office-based physicians.

RESULTS

The number of office visits with a recorded anxiety disorder diagnosis increased from 9.5 million in 1985 to 11.2 million per year in 1993–1994 and 12.3 million per year in 1997–1998, representing 1.9%, 1.6%, and 1.5% of all office visits in 1985, 1993–1994, and 1997–1998, respectively. The majority of recorded anxiety disorder diagnoses were not for specific disorders, with 70% of anxiety disorder visits to primary care physicians coded as “anxiety state, unspecified.” Visits to primary care physicians accounted for 48% of all anxiety disorder visits in 1985 and 1997–1998. Treatment for anxiety was offered in over 95% of visits to psychiatrists but in only 60% of visits to primary care physicians. Primary care physicians were less likely to offer treatment for anxiety when specific anxiety disorders were diagnosed than when “anxiety state, unspecified” was diagnosed (54% vs 62% in 1997–1998). Prescriptions for medications to treat anxiety disorders increased between 1985 and 1997–1998 while use of psychotherapy decreased over the same time period in visits to both primary care physicians and psychiatrists.

CONCLUSIONS

Although there is a large number of office visits with a recorded anxiety disorder diagnosis, under-recognition and under-treatment appear to be a continuing problem, especially in the primary care sector. Medication is being substituted for psychotherapy in visits to both psychiatrists and primary care physicians over time.