Eric J. Lenze

The Association of Late-Life Depression and Anxiety With Physical Disability: A Review of the Literature and Prospectus for Future Research

Depression and anxiety disorders are associated with excess disability. The authors searched the recent geriatric literature for studies associating late-life depression or anxiety with physical disability. Studies showed depression in old age to be an independent risk factor for disability; similarly, disability was found to be a risk factor for depression. Anxiety in late life was also found to be a risk factor for disability, although not necessarily independently of depression. Increased disability due to depression is only partly explained by differences in socioeconomic measures, medical conditions, and cognition. Physical disability improves with treatment for depression; comparable studies have not been done for anxiety. The authors discuss how these findings inform current concepts of physical disability and discuss the implications for future intervention studies of late-life depression and anxiety disorders.

The course of functional decline in older people with persistently elevated depressive symptoms: longitudinal findings from the Cardiovascular Health Study.

Objectives: To examine the relationship between persistently high depressive symptoms and long‐term changes in functional disability in elderly persons.

Maintenance Treatment of Depression in Old Age: A Randomized, Double-blind, Placebo-Controlled Evaluation of the Efficacy and Safety of Donepezil Combined With Antidepressant Pharmacotherapy

CONTEXTnCognitive impairment in late-life depression is a core feature of the illness.nnnOBJECTIVEnTo test whether donepezil hydrochloride and antidepressant therapy is superior to placebo and antidepressant therapy in improving cognitive performance and instrumental activities of daily living and in reducing recurrences of depression over 2 years of maintenance treatment.nnnDESIGNnRandomized, double-blind, placebo-controlled maintenance trial.nnnSETTINGnUniversity clinic.nnnPARTICIPANTSnOne hundred thirty older adults aged 65 years and older with recently remitted major depression.nnnINTERVENTIONSnRandom assignment to maintenance antidepressant pharmacotherapy and donepezil or to maintenance antidepressant pharmacotherapy and placebo.nnnMAIN OUTCOME MEASURESnGlobal neuropsychological performance, cognitive instrumental activities of daily living, and recurrent depression.nnnRESULTSnDonepezil and antidepressant therapy temporarily improved global cognition (treatment × time interaction, F₂,₂₁₆ = 3.78; P = .03), but effect sizes were small (Cohen d = 0.27, group difference at 1 year). A marginal benefit to cognitive instrumental activities of daily living was also observed (treatment × time interaction, F₂,₁₃₇ = 2.94; P = .06). The donepezil group was more likely than the placebo group to experience recurrent major depression (35% [95% confidence interval {CI}, 24%-46%] vs 19% [95% CI, 9%-29%], respectively; log-rank χ² = 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 of 30 participants (10% [95% CI, 0%-21%]) receiving donepezil and 9 of 27 participants (33% [95% CI, 16%-51%]) receiving placebo had a conversion to dementia over 2 years (Fisher exact test, P = .05). The mild cognitive impairment subgroup had recurrence rates of major depression of 44% with donepezil vs 12% with placebo (likelihood ratio = 4.91; P = .03). The subgroup with normal cognition (n = 73) showed no benefit with donepezil and no increase in recurrence of major depression.nnnCONCLUSIONSnWhether a cholinesterase inhibitor should be used as augmentation in the maintenance treatment of late-life depression depends on a careful weighing of risks and benefits in those with mild cognitive impairment. In cognitively intact patients, donepezil appears to have no clear benefit for preventing progression to mild cognitive impairment or dementia or for preventing recurrence of depression.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT00177671.

Generalized Anxiety Disorder in Late Life: Lifetime Course and Comorbidity With Major Depressive Disorder

OBJECTIVEnGeneralized anxiety disorder (GAD) in elderly persons is highly prevalent, but little is known about its course, age at onset, and relationship to comorbid major depressive disorder (MDD). The authors assessed the course and comorbidity of late-life GAD and MDD.nnnMETHODSnAuthors assessed elderly subjects in anxiety or depression intervention studies who had a lifetime history of GAD, with current MDD (N=57) or without (N=46). Subjects lifetime course of illness was charted retrospectively.nnnRESULTSnThe 103 subjects had a mean age of 74.1 years, and a mean age at onset of GAD of 48.8 years; 46% were late-onset. GAD episodes were chronic, and 36% were longer than 10 years. Of the comorbid GAD-MDD patients, most had different times of onset and/or offset of the disorders; typically, GAD preceded MDD.nnnCONCLUSIONSnElderly subjects with GAD tended to have chronic symptoms lasting years-to-decades, without interruption, and many have late onset. Elderly persons with lifetime GAD and MDD tend to have different onset and offset of the two disorders. Findings characterize late-life GAD as a chronic disorder distinct from MDD.

Onset of Depression in Elderly Persons After Hip Fracture: Implications for Prevention and Early Intervention of Late‐Life Depression

OBJECTIVES: To identify predictors of onset of major depressive disorder (MDD) and of depressive symptoms in subjects who suffered a hip fracture.

Physician office visits of adults for anxiety disorders in the United States, 1985–1998

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.

Time course of response to antidepressants in late-life major depression: Therapeutic implications

In the treatment of depression, there is considerable interest in the time course of response and, in particular, the speed with which individuals recover from depressive episodes. Examination of the time course and speed of response is critical for assessing the usefulness of specific treatments. However, while this issue has received attention in mid-life adult populations, it has received little consideration in the context of late-life major depression. The synthesis of empirical reports indicates that, while older adults with depression seem to respond with the same speed as mid-life adults, several factors have consistently been associated with reduced speed of response to antidepressant treatment, including greater severity of depressive symptoms and co-occurring anxiety symptoms. Limited evidence suggests that sleep impairment and genetic factors (e.g. presence of the s allele of the serotonin transporter gene promoter region) may also be associated with reduced speed of response. Some factors have consistently been found to be unrelated to speed of response (demographic characteristics, nonpsychiatric physical illnesses) whereas other factors have only mixed evidence supporting any effect (psychosocial and other clinical factors). While there is little work available to date, some evidence suggests that time course and speed of response affect longer-term outcomes of depression pharmacotherapy; thus, older adults with more rapid versus slower patterns of response may differ in the types of maintenance treatment needed to avert additional depressive episodes.None of potential strategies for accelerating speed of response have been clearly shown to be effective in late-life depression. Future treatment studies for late-life depression should routinely consider not only overall efficacy of a given pharmacotherapy (i.e. total rate of response), but time course and speed of response. To this end, new investigations must be designed to overcome the methodological limitations of prior studies that have examined time course and they should include a range of potential covariates and outcomes of between-patient differences in speed of response. Better understanding of factors related to such differences may suggest new intervention strategies to accelerate response.

Association of the Serotonin Transporter Gene-Linked Polymorphic Region (5-HTTLPR) Genotype With Depression in Elderly Persons After Hip Fracture

OBJECTIVEnThe authors examined the serotonin transporter gene-linked polymorphic region (5-HTTLPR) as a predictor of major depressive disorder and depressive symptoms after hip fracture, a common stressful medical event.nnnMETHODSnThis was a prospective, observational study of 23 elderly rehabilitation-hospital patients during their inpatient stay. Depressive symptoms were assessed by Hamilton Rating Scale for Depression (Ham-D) and PRIME-MD. Subjects were also genotyped for 5-HTTLPR.nnnRESULTSnSurvival analysis showed that genotype significantly predicted time-to-major depressive episode. Subjects with an s allele (genotype s/l or s/s) had significantly higher Ham-D scores over 14 weeks of follow-up than those with the l/l genotype.nnnCONCLUSIONnDepressive symptoms and major depressive disorder in elderly persons after a stressful medical event may be associated with 5-HTTLPR genotype. This finding requires confirmation in a larger sample.

Good treatment outcomes in late-life depression with comorbid anxiety

BACKGROUNDnLate-life depression studies have found that comorbid anxiety, as a symptom or comorbid disorder, is associated with poorer treatment response and increased likelihood of dropout. This study evaluated the impact of comorbid anxiety on response, dropouts, and side effects, in elderly subjects treated for depression.nnnMETHODSnWe analyzed data from a 12-week trial comparing nortriptyline and paroxetine in 116 patients aged 60 and older with depression. Subjects classified as having anxious depression were compared to those with nonanxious depression in terms of treatment response rate, time to response, dropout rate, and early side effects. The analysis was replicated with another study, in which 125 subjects aged 69 and older were treated openly with paroxetine and interpersonal psychotherapy.nnnRESULTSnAnxious and nonanxious groups did not differ in terms of response rates, time to response, dropout rates, or time to dropout. Side effects declined more quickly and more significantly in the anxious group than in the nonanxious group.nnnLIMITATIONSnSubjects were treated in a specialty mental health setting, and the findings may not apply in other settings.nnnCONCLUSIONSnWe found no association between comorbid anxiety and a poorer prognosis during acute treatment of late-life depression. For elderly patients with anxious depression, standardized treatment in the mental health sector is associated with a good response.

Effect of cerebrovascular risk factors on depression treatment outcome in later life.

OBJECTIVEnThe vascular depression hypothesis posits that depression can arise in late life from cerebrovascular damage and that depression arising this way has a different clinical presentation and is more chronic and treatment-resistant than early-onset depression. This study tested the relationship of cerebrovascular risk factors (CVRF) to clinical presentation and treatment outcome in 156 subjects enrolled in a long-term maintenance treatment study of late-life recurrent major depression.nnnMETHODSnCVRF scores were generated with the Probability of Stroke Risk Profile. Subjects with the highest one-third of scores were designated High CVRF, and their baseline clinical presentation and treatment outcomes were compared with the remaining subjects.nnnRESULTSnIn the High-CVRF group, a greater proportion of subjects had first-onset depression after age 60. However, high CVRF score, late onset of depression, and their interaction had no effect on time-to-remission, need for adjunctive medication, or increased risk for recurrence during 3-year follow-up. Furthermore, high CVRF score and late onset of depression did not predict the associated clinical features of vascular depression, such as psychomotor retardation and lack of insight, previously described in the literature.nnnCONCLUSIONnOptimism about the outcome of late-life depression treatment should not be diminished by the presence of high cerebrovascular risk.