Carolina Aponte Urdaneta, MD; and Mugdha Thakur, MD, are with the Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.
Dr. Aponte Urdaneta and Dr. Thakur have disclosed no relevant financial relationships.
Address correspondence to: Mugdha Thakur, MD, Department of Psychiatry and Behavioral Sciences, Box 3386, Duke University Medical Center, Durham, NC 27710.
According to the U.S. Census Bureau, the world’s 65-and-older population is projected to triple by midcentury, from 516 million in 2009 to 1.53 billion in 2050. In the United States, the population that is 65 and older will more than double by 2050, rising from 39 million in 2009 to 89 million.1
According to a U.S. Census Bureau release in September 2007, slightly more than 5% of the population 65 years or older occupies nursing homes, congregate care, assisted living, and board-and-care homes, and about 4.2% are in nursing homes at any given time. The rate of nursing home use increases with age from 1.4% of the young-old to 24.5% of the oldest-old. Nearly three-in-four residents of nursing facilities were 75 years or older. The median age of nursing facility residents was 83.2 years. Almost 50% of those 95 years and older lived in nursing homes. Women comprised approximately half of the total population but were nearly 70% of the nursing facility population.2
Depression is a common and disabling psychiatric disorder in later life. Nursing-home residents seem to be at increased risk. Prevalence of late-life depression in nursing homes varies among studies because of methodological differences. In a large epidemiological study carried out in the United States of 951 nursing facilities, with a total of 3,710 residents, the prevalence of identified depression was 20.3 cases per 100 residents.3 In one study in the Netherlands of 14 nursing homes, the prevalence of major depression was assessed to be 8.1%, the prevalence of minor depression was 14.1%, and 24% of the patients suffered from subclinical depression.4 In yet another study of a long-term care facility, 12.4% residents experienced major depression, and 35% experienced significant depressive symptoms.5 Thus, depression can be considered a highly prevalent disease in the nursing home population and requires proper diagnosis and management.
Late-life depression is a generic term that captures different diagnoses. It encompasses major depressive disorder, psychotic depression, dysthymia, minor depression, bereavement, adjustment disorder with depressed mood, and depression secondary to general medical condition.6 For the purpose of this review, we will consider major depressive disorder, minor depression, dysthymic disorder, and depression concurrent with Alzheimer’s disease. We will also comment briefly on depression comorbid with general medical conditions.
The etiology of late-life depression is multifactorial; thus, genetic, endocrine, neurotransmission, vascular, medical, psychological, and social factors contribute to it. Thus far, studies evidence a weaker genetic contribution in late-life depression than earlier in life. Although hypotheses have been proposed for the genes for serotonin synthesis, norepinephrine transport, and neurotrophic factor, further testing is required.7 Likewise, attention to neurotransmitter dysfunction has been a focus of study. 5HT2A receptor binding decreases in different brain regions through midlife (70% from the levels at 20 years through the fifth decade). Of note, these were normal subjects, and the activity of the receptors may vary with age.8 Endocrine changes in late life include diminished corticotrophin, including releasing factor and low testosterone levels (especially in men suffering with dysthymic disorder), both of which have been related to the development of depression.9,10 Also, chronic high cortisol levels, due to life-long stress, can result in neuronal death in the hippocampus; hippocampal atrophy has, in turn, been thought to be a result of depression.11–13
Vascular-based depression has been noted in elderly individuals, is associated with vascular changes in the brain and white matter hyperintensities, and is characterized by executive dysfunction.14–16 Structural abnormalities in the brains of depressed older patients seen on imaging include areas related to the limbic-cortical-striatal-pallidal-thalamus-cortical pathway,17 smaller size of the orbital frontal cortex in late-life depression,18 and smaller left hippocampal volumes in depressed patients who go on to develop dementia.13
Psychosocial factors leading to depression include the losses inherent in old age, such as those of health or significant others, as well as loneliness.19 Other themes proposed as causes of depression specific to the nursing home setting are loss of independence, freedom, and continuity with past life, feelings of social isolation, lack of privacy, loss of autonomy due to the institutional regimen and regulations, ambivalence toward cognitively impaired residents, staff turnover and shortage, stale programming, and lack of meaningful in-house activities.20
Religion may be a protective factor in development of depressive symptoms because these individuals who display “religious coping” show improved emotional and physical health.21,22 Wisdom is also thought to be a protective factor.6
Major Depressive Disorder
Older adults tend to differ somewhat from middle-aged adults in the presentation of depression symptoms.23 However, as with younger adults, the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) diagnostic criteria must be met for a diagnosis of Major Depressive Disorder. This is characterized by 2 weeks of either depressed mood or anhedonia, accompanied by an additional four of the following symptoms: changes in weight or appetite, decreased concentration, changes in sleep, psychomotor agitation or retardation, fatigue, feelings of worthlessness or excessive guilt, and recurrent thoughts of death or suicide.24 Of note, many older persons who have significant clinical depressive symptoms may not meet the above-mentioned criteria because their presentation of depression is atypical.25 Older adults are more likely to complain of loss of interest rather than overt depressed mood, and they are more likely to exhibit findings on neuropsychological testing showing cognitive impairment. Also, agitation is a frequent symptom of depression in the nursing home, as is weight loss. Older adults may ruminate about death during a depressive episode, although they are not as likely to express suicidal thoughts, especially in the inpatient and long-term care settings. Guilt is less frequent than in younger adults.19,26 Psychotic depression is frequently seen in the elderly, especially in the inpatient and long-term care settings. The most common delusions seen in the elderly are somatic and persecutory delusions.27 In the nursing home, an older depressed patient may be overtly delusional yet cooperative and easily managed due to decreased functional capacity.19
Minor depression is diagnosed according to Appendix B of DSM-IV-TR when one of the core symptoms of major depression is present, along with one to three additional symptoms.24 It is a relevant diagnosis in the elderly because it has associations that are similar to those of major depression, including impaired physical functioning, poorer self-rated health, and use of psychotropic medications.25,28 It has also been defined as a score of 16 or less on the Center for Epidemiologic Studies Depression Scale (CES-D) but not meeting criteria for clinically significant depression.29
By DSM-IV-TR definition, individuals experience depressed mood for most of the day and for the majority of days of a 2-year period without meeting criteria for major depression.24 This entity can persist from midlife into late life, but it rarely has onset in late life.30
Depression Concurrent with Alzheimer’s Disease (AD)
Late-life depression and cognitive impairment can often co-occur.31 Individuals with depression and cognitive impairment are at greater risk of developing AD or vascular dementia.32,33 Studies show that 30% to 50% of individuals with AD experience symptoms of depression, including low mood, apathy, social withdrawal, and suicidal ideation.34 Major depression is common among patients with mild (11.5%) and moderate (10%) AD, but occurs at a lower rate in severe AD (4.5%).35 Some investigators have recently proposed criteria for the diagnosis of depression in AD. The presence of three of the following symptoms in a 2-week period would qualify for the diagnosis of comorbid depression: depressed mood, anhedonia, social isolation, poor appetite, poor sleep, psychomotor changes, irritability, fatigue and loss of energy, feelings of worthlessness, and suicidal thoughts.19,36
Screening and Diagnostic Work-Up
The mainstay for diagnosis is based on a thorough history, including personal or family history of past depressive episodes, history of suicidality, and history of substance abuse. Also important are past treatment trials and response, and assessment of current suicidal ideation and imminent risk of self harm; a complete physical examination to rule out comorbidities should also be performed.6,19
Screening for depression with a standardized scale that has been validated, such as the Geriatric Depression Scale (GDS)37,38 and the CES-D29 can aid with the diagnosis. Cognitive status should be assessed with the Mini-Mental State Examination (MMSE), given the high likelihood of comorbid depression and cognitive dysfunction.39
In patients with cognitive impairment and depressive symptoms, the clinician needs to contact the family, as well as the nursing staff, who have regular interaction with the patient, to obtain the history. The Cornell Scale for Depression in Dementia is a scale that is sensitive to change in cognitively impaired individuals.40 This scale was developed recognizing that patients and their caregivers individually may not provide all relevant clinical information and that individual depression symptoms fluctuate over time.41 The scale has been shown to have high inter-rater reliability and sensitivity.42 Laboratory work-up includes basic metabolic panel, complete blood count, thyroid function tests, and serum vitamin B12 and folate levels to rule out medical conditions that can mimic depression such as hypothyroidism, anemia, electrolyte abnormalities, and vitamin B12 or folate deficiencies.6,19 It is important to evaluate the nutritional status in the depressed elder, especially in the oldest old, given the risk for frailty and failure to thrive.
A complete review of the medications the patient is on and reduction of polypharmacy as well as, when possible, discontinuation of medications that may be contributing with depressive symptoms is warranted.
Selective serotonin reuptake inhibitors (SSRIs) are the preferred agents and have become the drugs of first choice in the treatment of mild to moderate depression in the elderly because of their safety and tolerability profile.43 Several randomized, controlled trials for the treatment of acute geriatric depression have been conducted; however, most of them have not been conducted in the nursing home setting, and in general, they do not have a placebo-controlled group. Typically, studies have not selected the oldest geriatric patients who are overrepresented in nursing home populations. Current evidence-based treatment of depression in long-term care comprises of extrapolating evidence from broader studies of older adults and applying it judiciously to frail patients seen in long-term care.
Eight trials have been published on citalopram, which is the most selective SSRI available. Citalopram was more efficacious than placebo for poststroke depression in a 6-week trial.44 It was as efficacious as venlafaxine in a group of depressed elderly patients with no cognitive impairment.45 Compared with amitriptyline, in two trials, citalopram proved to be equally efficacious and significantly better tolerated.46,47 Compared with nortriptyline, citalopram had better tolerability but lower remission rate.48 In a trial of 147 patients with medical comorbidities or cognitive impairment, citalopram improved significantly more than the placebo group.49 In yet another trial with patients with Alzheimer’s dementia (AD) and vascular dementia, citalopram showed a significant improvement in emotional bluntness, confusion, irritability, anxiety, fear/panic, depressed mood and restlessness, compared with placebo. However, there were no significant improvements in patients with vascular dementia.50 There was a negative trial studying 174 “old-old” (75 years and older), in which citalopram was no more effective than placebo; this could be attributed to high rates of placebo response.51
Escitalopram has not proven to be effective for the acute treatment of geriatric depression, in the one randomized control trial (RCT) that we found.52 It has, however, been efficacious in the prevention of relapse in another study.53
There have been 12 RCTs on the treatment of elderly depression with fluoxetine. Fluoxetine proved to be more efficacious than placebo in three of six trials.54–56 Fluoxetine has been shown to be as efficacious as amitriptyline,57,58 doxepin,59 sertraline,60 escitalopram,52 venlafaxine,61 paroxetine,62 trimipramine.63 In dysthymia, it was found to have limited efficacy and to be just slightly better than placebo.56 The results were negative for a trial in patients with AD.64
Sertraline, in turn, has had 11 RCTs, and its efficacy was superior than placebo in patients with and without medical comorbidites.65,66 Likewise, it was superior to placebo in a trial with patients with depression and AD.67 Sertraline was similarly effective to nortriptyline,68,69 amitriptyline,70 fluoxetine,60,71 imipramine,72 venlafaxine,73 and fluvoxamine.74 Greater cognitive improvement was obtained with sertraline in comparison with fluoxetine and nortriptyline in elderly depressed patients.75 Fluvoxamine was comparable to mianserinm,76 dothiepin,77 sertraline,74 and imipramine.78 In the latter study, which was also placebo controlled, fluvoxamine was more efficacious than placebo.
Paroxetine has proven to be more efficacious than placebo.79 In the 10 RCTs to date, it has also shown similar efficacy to amitriptyline,80 bupropion,81,82 clomipramine,83 doxepin,84 fluoxetine,62 nortriptyline,85 and imipramine.86 Of note, in a small trial, in very old population in long-term care, paroxetine was more cognitively impairing than placebo and was not significantly more efficacious.87
Venlafaxine has had one negative trial.61 It has been found to be less well tolerated than sertraline and fluoxetine, but better tolerated than clomipramine, trazodone, and dothiepin. It has proven to be as efficacious as citalopram,45 clomipramine,88 dothiepin,89,90 fluoxetin,61 nortriptyline,91 and sertraline.73 It has demonstrated better efficacy that trazodone.88
There are two trials that find duloxetine to be efficacious and significantly superior than placebo in the treatment of late-life depression.92,93 Of note, this medication also showed efficacy on pain measures.
Bupropion was as efficacious as imipramine and significantly superior than placebo in a small controlled trial.94 It also showed comparable efficacy to paroxetine in two different trials.81,82
Mirtazapine was similar in efficacy as low-dose amitriptyline.95 It was marginally superior compared with proxetine, with better tolerability.96 One 6-week, placebo-controlled trial was found comparing mirtazapine, trazodone, and placebo. Mirtazapine was found to be superior to placebo.97
Methylphenidate has been found to be superior than placebo in at least one small RCT with elderly, medically ill patients.98 (See Table for summary of evidence, page 24.)
Table. Summary of the Pharmacologic Evidence
Tolerability and Side Effects
The decision about antidepressant choice in older adults is guided as much by efficacy as by the side-effect profile of the drug. As a rule, the starting dose should be half the recommended starting dose, and titration should be gradual. Important advantages of the use of newer antidepressants over tricyclic antidepressants (TCAs) include lack of cardiac, anticholinergic and orthostatic side effects, as well as in general lack of sedation. Even so, the newer antidepressants are not without side effects. With almost all antidepressants, there can be initial gastrointestinal side effects, headaches, and increased anxiety, most of which subside with time.19 Certain side effects of SSRIs and serotonin-norephinephrine reuptake inhibitors (SNRIs) can be more serious in the elderly. There is a definite risk for developing hyponatremia because of a syndrome of inappropriate secretion of antidiuretic hormone, and patients should have sodium levels checked before and after commencement of antidepressant medications.99 Other serious side effects reported with SSRIs include excessive activation and weight loss,6 risk of falls,100 and hip fractures,101 serotonin syndrome,102 gastrointestinal bleeding,103 and insomnia or sleep disturbances.104
Electroconvulsive Therapy (ECT)
ECT continues to be the most effective form of treatment for severe and/or psychotic major depression.105 It is a treatment reserved for those who have failed pharmacotherapy, cannot tolerate medications, or who present with self-destructive behaviors, such as refusal to eat or suicide attempt. The overall success rate of ECT is about 80%, and the literature suggests that this is the case in older adults, as well.106,107 Of note, ECT treatment can lead to memory difficulties, and patients with dementia can experience worsening of their cognition.108 However, studies have shown that, over time, ECT may lead to significant improvement in memory of cognitively impaired older patients with depression.109 Thus, ECT is a safe and effective treatment for older adults and not contraindicated in nursing home patients.
Light Therapy and Exercise
Noticing that institutionalized patients may spend too much time in their rooms and have decreased exposure to sun light and chronic light deprivation, a study was conducted to investigate the efficacy of morning bright-light treatment on depression among older adults residing in a long-term care facility. It showed that 30 minutes of bright light daily improved depression.110 Likewise, patients that are in long-term care settings may be less mobile and have decreased physical activity, especially if suffering from medical comorbidities. In this context aerobic exercise has been found to be as effective as medication in geriatric depression treatment at 16 weeks.111 In one study of treatment of depressed patients with dementia in a nursing home setting, therapeutic biking with a “wheelchair bicycle” was found to be effective in treating depression, with gains maintained at 10 weeks’ follow-up.112 A study conducted in United Kingdom showed that group exercise was less effective, especially if the patients where cognitively impaired.113
Several studies of different forms of psychotherapy, including cognitive, behavioral, brief dynamic, cognitive behavioral, bibliotherapy, reminiscence and general psychotherapies, have proven to promote significant improvement and to be more effective compared with placebo and were of comparable efficacy compared with each other114–116 in the management of geriatric depression. Combination treatment with medication and interpersonal psychotherapy is better than either medication or psychotherapy alone in preventing recurrence of depression in the elderly.117
The long-term care setting may be ideal to implement cognitive behavioral approaches, as well as wellness charts or pleasant events schedule. A review of the available literature on psychotherapy in the long-term care suggests positive efficacy of different approaches, with significant short-and, in some cases, longer-term benefits on instruments measuring depression, hopelessness, self-esteem, perceived control, and a host of other psychological variables. Nevertheless, these findings must be interpreted with caution in view of methodological limitations of many studies, including small sample sizes, variable study entry criteria, short-duration trials, heterogeneous outcome assessment methods, and lack of detail on intervention methods.117 More studies regarding efficacy outcomes specific to this setting are needed.
One study of older patients with depression in the clinical setting showed that patients recovered and sustained remission in 35% of cases, 48% had a fluctuating course or remained ill, and 14% died.118 In another study, at follow-up 6 years after initial evaluation, older adults who had been depressed experienced impairment in activities of daily living in 67% of the cases and restrictions of mobility in 73% of cases.119
Depressive disorders are highly prevalent in elderly individuals in nursing homes. Recognition and treatment are important in preventing further comorbidity and death, as well as unnecessary suffering. Screening tools available have been validated and are easily used. It is important to rule out medical conditions that can mimic depression in the process of evaluation. The evidence is ever growing for pharmacotherapy and psychotherapy, and the physician has available several different tools to use, taking into close account the presenting symptoms, as well as the medications side effect profile. Nonpharmacologic interventions are promising as well, and, when available, should be considered.
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Summary of the Pharmacologic Evidence
|Medication||Number Published of Trials (ref #)||Placebo-controlled Trials||Negative Trials||Nursing Home-conducted Trials||Summary of Findings|
|Citalopram||8 (44–51)||4 (44,49–51)||1 (51)||0||Citalopram was more efficacious than placebo in three of four trials. Negative trial was in “old-old” population, with high placebo response. Equally efficacious to amytryptiline and venlafaxine. Better tolerated but less efficacious than nortryptyline.|
|Escitalopram||2 (52,53)||2 (52,53)||1 (52)||0||Escitalopram was not superior to placebo in one trial. It was more efficacious than placebo in preventing relapse of MDD in another trial.|
|Fluoxetine||12 (52,54–64)||6 (52,54–56,61,64)||3 (52,61,64)||0||Fluoxetine was superior to placebo in three of the six placebo-controlled trials. It was equally efficacious to doxepin, amitripytline, escitalopram, paroxetine, sertraline, trimipramine, and venlafaxine.|
|Sertraline||11 (65–75)||3 (65–67)||0||2 (69,73)||Sertraline was more efficacious than placebo and equally efficacious to amitriptyline, fluoxetine, fluvoxamine, imipramine, nortriptyline, and venlfaxine.|
|Fluvoxamine||4 (74,76–78)||1 (78)||0||0||Fluvoxamine was superior to placebo in one study and equally efficacious to dothiepin, imipramine, mianserin, and sertraline.|
|Paroxetine||10 (62,79–87)||2 (79,87)||1 (87)||1(87)||Paroxetine was more efficacious than placebo in one trial and had negative results in another trial. It is as efficacious as amitriptyline, bupropion, clomipramine, doxepin, fluoxetine, and impramine.|
|Venlafaxine||7 (45,61,73,88–91)||1 (61)||1 (61)||1 (73)||Venlafaxine did not prove to be superior to placebo. It has shown to be as efficacious as citalopram, clomipramine, dothiepin, fluoxetine nortriptyline, and sertraline and more efficacious than trazodone.|
|Duloxetine||2 (92,93)||2 (92,93)||0||0||Duloxetine proved superior to placebo in the two trials conducted thus far.|
|Bupropion||3 (81,82,94)||1 (94)||0||0||Bupropion was superior to placebo and as efficacious as imipramine and paroxetine.|
|Mirtazapine||2 (95,96)||1 (97)||0||0||Mirtazapine was as efficacious as amitriptyline and slightly more efficacious than paroxetine. One placebo controlled trial with mirtazapine being superior to placebo.|
|Methylphenidate||1 (98)||1 (98)||0||0||Methylphenidate was superior to placebo in a small RCT.|