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Depression in the Elderly
 
 
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Aging Database Needed
 
from Jules: there is no research nor data on what aging HIV+ experience clinically except the studies reporting comorbidities like bone & heart disease etc increasing in patients & increased comorbidities, but what is lacking are studies in patients specifically in their 60s & 70s and what they are experiencing in terms of precise comorbidities, polypharmacy, depression, mental health, frailty, gait, capacity for independent activities, suicide, suicide ideation, loneliness etc. There should be a database collecting all this information in patients in their 60s & 70s. BUT there is a CNICS database, which is a cohort of HIV+ being followed that includes 7000 between 50-59, 2000 60-69 and 344 >70 in age patients. http://www.uab.edu/cnics/data-core/cnics-data-elements
 
As well we do not have a project to deliver a set of support services to these patients & an evaluation; except their 2 US aging clinic at Cornell in NY and at UCSF in SF: HIV & Aging in SF: age-57; 35-60% Impairment - (04/12/16)
 
Aging with HIV program At the Center for Special Studies (CSS), the adult HIV practice at Weill Cornell Medicine/New York Presbyterian Hospital
http://www.aahivm.org/HIV_Specialist/upload/FINAL MARCH 2016.pdf
 
"In light of near-normal lifespans for PLHA, a recent Dutch study projected that by 2030, 73% of those infected with HIV will be at least 50 years of age and 39% will be 60 years or older.2
 
Those who are over 50 years of age must contend with HIV infection and aging simultaneously, and the current workforce is unprepared to care for this aging population"
 
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"Late-life depression is the occurrence of major depressive disorder in adults 60 years of age or older. Major depressive disorder occurs in up to 5% of community-dwelling older adults, and 8 to 16% of older adults have clinically significant depressive symptoms.1 Rates of major depressive disorder rise with increasing medical morbidity, with reported rates of 5 to 10% in primary care2 and as high as 37% after critical care hospitalizations.3
 
Patients with late-life depression are heterogeneous in terms of clinical history and coexisting medical conditions. As compared with older adults reporting an initial depressive episode early in life, those with late-onset depression are more likely to have neurologic abnormalities, including deficits on neuropsychological tests and age-related changes on neuroimaging that are greater than normal; they are also at higher risk for subsequent dementia. 4 Such observations informed the hypothesis that vascular disease may contribute to depression in some older adults"
 
"Conclusions and Recommendations
 
The patient described in the vignette is having a first episode of depression and also has some memory problems. It is crucial to ask about suicidal thoughts, alcohol use, and coexisting medical illnesses. First-line treatment could involve either pharmacotherapy or psychotherapy (in particular, problem-solving therapy, because it has been shown to benefit depressed patients who also have cognitive impairment); the choice would depend on the patient's preference and the availability of psychotherapy. If medication were used, the recommended initial therapy would be administration of an SSRI, starting at a low dose (e.g., sertraline at a daily dose of 25 mg) in order to assess the patient for side effects and then increasing to a minimum therapeutic dose (50 mg daily in the case of sertraline). Higher doses may be needed for maximal efficacy (e.g., 100 mg or more of sertraline daily), with close attention to side effects. If the depressive symptoms are not sufficiently reduced, I would consider a change to an SNRI, such as venlafaxine. Screening for cognitive deficits should be performed and formal neuropsychological testing should be considered if cognitive symptoms persist or worsen despite antidepressant therapy.
 
It is unclear how best to address cognitive deficits in patients with late-life depression. Cognitive impairment is predictive of a poor response to antidepressants38,39; even with remission of depression, deficits may persist and signal a high risk of dementia.
 
Brain Stimulation: Electroconvulsive therapy (ECT) is the most effective treatment for severely depressed patients, including elderly patients. Although antidepressant medication is first-line therapy, ECT should be considered in patients if they are suicidal, have not had a response to antidepressant pharmacotherapy, have a deteriorating physical condition, or have depression-related disability that threatens their ability to live independently. Available data from open-label trials, typically involving persons who had not had a response to antidepressants, suggest remission rates of 70 to 90% with ECT, although remission rates in community samples may be lower (30 to 50%).”
 
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Depression in the Elderly
Warren D. Taylor, M.D., M.H.Sc.
N Engl J Med 2014
 
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations.
 
A 74-year-old woman with hypertension that is well controlled with hydrochlorothiazide is brought by her daughter for an evaluation. The daughter states that her mother is withdrawn, often tearful, and at times appears to have memory problems but has no history of psychiatric illness. The patient is a retired teacher who is widowed and has lived independently for several years. During the last few months, she has stopped going to church and visiting friends. The patient's symptoms include irritability, anhedonia, fatigue, a 4.5-kg (10-lb) weight loss over a period of 3 months, and difficulty sleeping. She feels like a burden to her family. How should she be treated?
 
The Clinical Problem
 
Late-life depression is the occurrence of major depressive disorder in adults 60 years of age or older. Major depressive disorder occurs in up to 5% of community-dwelling older adults, and 8 to 16% of older adults have clinically significant depressive symptoms.1 Rates of major depressive disorder rise with increasing medical morbidity, with reported rates of 5 to 10% in primary care2 and as high as 37% after critical care hospitalizations.3
 
Patients with late-life depression are heterogeneous in terms of clinical history and coexisting medical conditions. As compared with older adults reporting an initial depressive episode early in life, those with late-onset depression are more likely to have neurologic abnormalities, including deficits on neuropsychological tests and age-related changes on neuroimaging that are greater than normal; they are also at higher risk for subsequent dementia. 4 Such observations informed the hypothesis that vascular disease may contribute to depression in some older adults.5,6
 
Key Clinical Points
 
Depression in the Elderly

 
⋅ Late-life depression (occurring in persons 60 years of age or older) is common and is often associated with coexisting medical illness, cognitive dysfunction, or both.
⋅ Depressed older adults are at increased risk for suicide.
⋅ Screening for depression is important, but positive screening results should be followed by a thorough evaluation to assess patient safety and ensure that treatment is warranted.
 
⋅ Either pharmacotherapy or psychotherapy may be used as first-line therapy.
⋅ Currently available antidepressants show efficacy in depressed older populations, but older adults may be at increased risk for medication side effects. Selective serotonin-reuptake inhibitors (SSRIs) are considered first-line pharmacotherapy.
⋅ Standardized psychotherapy techniques are also effective for depression in older adults.
 
The diagnostic criteria for major depression in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), require the presence of either sadness or anhedonia with a total of five or more symptoms over a 2-week period (Table 1). Low mood may be less common in older adults with depression than in younger adults with the disorder, whereas irritability, anxiety, and somatic symptoms may be more common. Psychosocial stressors such as the death of a loved one may trigger a depressive episode, although transient reactions to major losses can resemble depression. In DSM-5, unlike previous editions, grief after the death of a loved one is not considered to be exclusionary.
 
Coexisting medical illness complicates the management of depression. Persons with late-life depression have higher rates of coexisting conditions and concomitant medication use than their nondepressed counterparts. The relationship between depression and a coexisting medical illness may be bidirectional: medical problems such as chronic pain may confer a predisposition to depression, and depression is associated with worse outcomes for conditions such as cardiac disease. 7 Coexisting illness raises concerns about polypharmacy, including the effects of psychotropic drugs on medical conditions and the metabolism of other medications. Age-related declines in drug metabolism may also contribute to increased rates of medication side effects.
 
Coexisting cognitive impairment is common in persons with late-life depression and can involve multiple cognitive domains, including executive function, attention, and memory. Depression may be both a risk factor for and a manifestation of cognitive decline: depression is associated with an increased long-term risk of dementia.8 Cognitive deficits may thus be signs of accelerated brain aging that confers a predisposition to and perpetuates depression.6
 
Strategies and Evidence
 
Evaluation

 
The U.S. Preventive Services Task Force recommends depression screening if support is in place to ensure accurate diagnosis and appropriate treatment and follow-up, and annual depression screening is now covered by Medicare Part B. However, screening without a subsequent confirmatory evaluation leads to false positive diagnoses and unnecessary treatment.9 To fully evaluate depression, clinicians should use validated measures, such as the Patient Health Questionnaire 9, that reflect diagnostic criteria (Table 1). Because older adults, particularly elderly white men, have high suicide rates,10 the presence of suicidal thoughts should be carefully explored.
 
Important features of the history are summarized in Table 2 Warning signs supporting urgent intervention include severe or worsening symptoms, suicidality, and impairment in daily functioning. Recommended laboratory tests include blood counts to test for anemia and measurement of the glucose level, as well as measurement of thyrotropin, since hypothyroidism can mimic depressive symptoms. Measurement of serum levels of vitamin B12 and folate is also commonly recommended, because the prevalence of vitamin B12 deficiency increases with age, and low levels of vitamin B12 and folate may contribute to depression. Cognitive screening (e.g., with the Mini-Mental State Examination) is warranted in persons reporting memory problems and may reveal deficits in visuospatial processing or memory even if the total score is in the normal range. Neuropsychological testing may help identify early dementia, but because acute depression negatively affects performance, testing should be postponed until depressive symptoms diminish.
 
Treatment
 
Lifestyle Changes

 
Depressed older adults should be encouraged to increase their physical activity to the extent that they can. In a meta-analysis of seven randomized, controlled trials, moderate-intensity exercise reduced depressive symptoms.11 Other reasonable recommendations include improving nutrition and increasing engagement in pleasurable activities and social interactions. However, because depression increases the challenge of initiating lifestyle changes, these recommendations are generally insufficient in the absence of other interventions, such as pharmacotherapy, psychotherapy, or both.
 
Pharmacotherapy
 
Owing to their favorable adverse-event profiles and low cost, selective serotonin-reuptake inhibitors (SSRIs) are first-line treatments for late-life depression (Table 3Table 3Antidepressants Commonly Used to Treat Late-Life Depression.). In some randomized, controlled trials,12,13,15,16 but not others,17-19 SSRIs such as sertraline, fluoxetine, and paroxetine have been more effective than placebo in reducing depressive symptoms and increasing rates of remission of depression. Generally, trials that showed a significant benefit in patients with late-life depression were larger than those that did not; for example, trials showing a benefit of sertraline included more than 350 participants in each study group.12,13 In the largest studies,12,13,15,16 rates of SSRI response (defined as ≥50% reduction in the severity of depression) ranged from 35 to 60%, as compared with placebo response rates of 26 to 40%. Although not reported for all studies,12,13 remission rates (defined as a minimal level of depressive symptoms) were 32 to 44% with SSRIs versus 19 to 26% with placebo.15,16 SSRIs may also effectively treat severe depression: although a randomized trial did not show a significant difference in remission rates between citalopram and placebo, a post hoc analysis suggested that severely depressed patients were more likely to have a remission with citalopram (35% vs. 19%).19
 
Common adverse effects of SSRIs, which are typically mild, include nausea and headache (Table 3). Of concern are reports noting a higher risk of stroke among persons taking SSRIs than among nonusers of antidepressants (annualized stroke rate of approximately 4 vs. 3 per 1000 person-years in one report20). However, a similar increase in the risk of stroke has been noted with other antidepressant classes, and it is unclear to what extent the increased risk may be explained by the underlying depression or other associated factors.
 
Serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly used as second-line agents when remission is not obtained with SSRIs. In small studies, venlafaxine did not show greater efficacy than placebo,21,22 but a larger, placebo-controlled trial of duloxetine showed significant improvements in late-life depression (response rate, 37% vs. 19%; remission rate, 27% vs. 15%). 14 As observed in trials involving younger adults, randomized trials involving older adults have not shown significant differences between the benefits of SSRIs and those of SNRIs, although adverse effects may be more frequent with SNRIs.21,22
 
Tricyclic antidepressants have efficacy similar to that of SSRIs in the treatment of late-life depression23 but are less commonly used owing to their greater side effects (Table 3). If SSRIs or SNRIs are ineffective, tricyclic antidepressants may be considered (either as monotherapy or as augmentation). However, tricyclic antidepressants are included in the Beers Criteria list of potentially inappropriate medications associated with high rates of adverse drug events among older adults.24
 
Open-label and small, controlled trials support the use of bupropion (response rate, 71%)25 and mirtazapine (response rate, 47%)26 in patients with late-life depression; however, data from rigorous placebo-controlled trials are lacking. Despite occasional clinical use, there have been no large, robust, controlled trials of stimulants in depressed older adults. 27
 
Since their approval for adjunctive use in treatment-resistant depression, the second-generation antipsychotic agents olanzapine and aripiprazole have been increasingly used in the treatment of nonpsychotic depression.28 In open-label studies, 50% of depressed older adults who did not have a full response to an antidepressant were reported to have a remission with aripiprazole augmentation.29,30 However, these trials are limited by the lack of blinding and the lack of a control group. A pooled subgroup analysis incorporating data from three placebo-controlled trials involving mostly younger adults showed that among adults 50 to 67 years of age, remission rates with 6 weeks of aripiprazole augmentation were higher than with placebo augmentation (32.5% vs. 17.1%).31These remission rates did not differ significantly from rates among younger adults. Akathisia was the most common side effect in this population, occurring in 17% of older patients. Longer-term safety and efficacy data in older patients are needed.
 
Psychotherapy
 
Psychotherapies are effective treatments for late-life depression and may be considered as first-line therapy, depending on availability and patient preference. Standardized psychotherapeutic approaches include a short-term treatment phase, consisting of weekly visits over a period of 8 to 12 weeks. Some persons may require a longer period of treatment or may require less frequent sessions after short-term treatment. Although other therapies may also be effective, the evidence base for short-term treatment is strongest for cognitive behavioral therapy and problem-solving therapy. However, generalizability is a concern because most studies of psychotherapy for late-life depression have involved cognitively intact, well-educated, white, and relatively young geriatric populations.32 Cognitive behavioral therapy focuses on identifying and reframing negative, dysfunctional thoughts while increasing participation in pleasurable and social activities. A meta-analysis of 23 randomized, controlled trials showed that cognitive behavioral therapy was significantly more effective in reducing depressive symptoms than treatment as usual or placement on a wait list for treatment but was not more effective than other psychotherapies.33 However, it may have a weaker effect in physically ill or cognitively impaired persons.34 More recent trials assessing Internet-based approaches to cognitive behavioral therapy also show efficacy for depression; however, older adults are poorly represented in these studies and may require help navigating the website or using the computer.35
 
Problem-solving therapy focuses on the development of skills to improve the ability to cope with life problems. Randomized trials involving older adults have shown that problem-solving therapy results in greater improvements in depression than usual care or reminiscence therapy,36 a psychotherapy focusing on the evaluation and reframing of past life events. Problem-solving therapy effectively treats depressive symptoms in older adults with cognitive deficits (specifically, coexisting executive dysfunction),37 a group that often has a poor response to antidepressant medications. 38,39 In a trial involving a cognitively impaired population, problem-solving therapy resulted in higher remission rates than supportive therapy (46% vs. 28% at 12 weeks).37 Problem-solving therapy also results in greater improvement in disability than does supportive therapy, with benefits maintained for at least 24 weeks.40
 
Interpersonal therapy for older adults with depression focuses on role transitions, grief, and interpersonal issues. In randomized trials, interpersonal therapy resulted in significantly greater reductions in depressive symptoms than usual treatment.41 As with cognitive behavioral therapy, persons with coexisting medical conditions or cognitive deficits may not have a good response to interpersonal therapy.42
 
Maintenance Therapy
 
Longitudinal studies have shown a significant benefit of continued treatment after remission. One study involved older adults with recurrent depression who had a short-term remission with nortriptyline and interpersonal therapy over a period of 16 weeks. Study participants were randomly assigned to maintenance therapy with nortriptyline or placebo and to monthly maintenance psychotherapy (interpersonal therapy) or no psychotherapy. After 3 years, relapse rates were significantly lower among persons assigned to continued treatment with nortriptyline alone (43%), nortriptyline and interpersonal therapy (20%), or interpersonal therapy alone (64%) than among persons receiving placebo and no interpersonal therapy (90%)43; the combination of nortriptyline and interpersonal therapy was significantly more effective than interpersonal therapy alone. However, in a similarly designed study involving mostly patients with a first episode of depression, maintenance treatment with paroxetine (alone or with interpersonal therapy), but not with interpersonal therapy alone, reduced the risk of relapse at 2 years, as compared with no active maintenance therapy.42 Data from long-term randomized, controlled trials are lacking to assess the efficacy of maintenance treatment with either cognitive behavioral therapy or problem-solving therapy for late-life depression.
 
Brain Stimulation
 
Electroconvulsive therapy (ECT) is the most effective treatment for severely depressed patients, including elderly patients. Although antidepressant medication is first-line therapy, ECT should be considered in patients if they are suicidal, have not had a response to antidepressant pharmacotherapy, have a deteriorating physical condition, or have depression-related disability that threatens their ability to live independently. Available data from open-label trials, typically involving persons who had not had a response to antidepressants, suggest remission rates of 70 to 90% with ECT, although remission rates in community samples may be lower (30 to 50%).44 Data from high-quality blinded, sham-controlled studies using modern ECT techniques are lacking. In addition, randomized trials show high subsequent relapse rates (40 to 50% in the 6 months after treatment).45 Current ECT protocols are safe, with few contraindications. Common side effects include postictal confusion with both anterograde and retrograde amnesia; current administration techniques, such as unilateral electrode placement with a brief pulse, substantially reduce this risk, and cognitive symptoms typically resolve after the completion of ECT. Persons with cardiovascular or neurologic disease are at increased risk for ECT-related memory problems.
 
Transcranial magnetic stimulation is a newer treatment for depression that uses a focal electromagnetic field generated by a coil held over the scalp, most commonly positioned over the left prefrontal cortex. Sessions are scheduled five times a week over a period of 4 to 6 weeks. In a trial involving mostly younger depressed adults, transcranial magnetic stimulation was superior to sham treatment (remission rate, 14% vs. 5%).46 This treatment does not require anesthesia and does not have cognitive side effects. However, a meta-analysis of six trials comparing transcranial magnetic stimulation with ECT showed that ECT has higher remission rates.47 Although a large multisite trial did not show that age was a significant predictor of response,48 other studies have suggested that depressed older adults may not have as robust a response as younger adults.49
 
Areas of Uncertainty
 
Randomized trials are needed to evaluate the efficacy and risks of many treatments currently used for late-life depression. For many antidepressants, data on efficacy and safety in older populations are scarce or absent, so treatment decisions are often guided by data from younger adults. However, there may be increased risks specific to older populations.20 Data on long-term pharmacotherapy and psychotherapy maintenance strategies in older populations are also limited.
 
It is unclear how best to address cognitive deficits in patients with late-life depression. Cognitive impairment is predictive of a poor response to antidepressants38,39; even with remission of depression, deficits may persist and signal a high risk of dementia. In a blinded, placebo-controlled trial of donepezil as an adjunct to antidepressant therapy for the maintenance treatment of depression, the donepezil group had, at best, modest and transient improvement in cognitive measures over a 2-year period and a significantly higher risk of depression recurrence50; post hoc analyses suggested that these effects were limited to patients with concomitant mild cognitive impairment. Neither memantine, a drug approved for the treatment of Alzheimer's disease, nor stimulants such as methylphenidate have been shown to have cognitive benefits in patients with late-life depression.
 
Guidelines
 
The recommendations provided here are consistent with American Psychiatric Association practice guidelines for the treatment of major depressive disorder, which include recommendations for the treatment of older adults.51 These guidelines highlight the need for careful evaluation of suicide risk and coexisting medical conditions in this population.
 
Conclusions and Recommendations
 
The patient described in the vignette is having a first episode of depression and also has some memory problems. It is crucial to ask about suicidal thoughts, alcohol use, and coexisting medical illnesses. First-line treatment could involve either pharmacotherapy or psychotherapy (in particular, problem-solving therapy, because it has been shown to benefit depressed patients who also have cognitive impairment); the choice would depend on the patient's preference and the availability of psychotherapy. If medication were used, the recommended initial therapy would be administration of an SSRI, starting at a low dose (e.g., sertraline at a daily dose of 25 mg) in order to assess the patient for side effects and then increasing to a minimum therapeutic dose (50 mg daily in the case of sertraline). Higher doses may be needed for maximal efficacy (e.g., 100 mg or more of sertraline daily), with close attention to side effects. If the depressive symptoms are not sufficiently reduced, I would consider a change to an SNRI, such as venlafaxine. Screening for cognitive deficits should be performed and formal neuropsychological testing should be considered if cognitive symptoms persist or worsen despite antidepressant therapy.

 
 
 
 
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