Late-Life Depression

Nov 01, 2008

Late-life depression is both underrecognized and undertreated. The impact of medical comorbidity may mask depressive symptoms.

In 2001, depressive disorders were the third leading cause of disability in Western industrialized countries.1 The cost of depression in the United States alone, in 2000, was estimated to be more than $83 billion.1 Of this, $26.1 billion were medically related costs, $51.5 billion were work-related costs, and $5.4 billion were related to suicidal mortality.2 The prevalence of depression is higher among persons with comorbid medical conditions than in those with no comorbidity. Some conditions that are common in older people, such as stroke, cardiac disease, chronic obstructive pulmonary disease (COPD), and diabetes mellitus, are associated with particularly high rates of depression comorbidity.3-5

Late-life depression is both underrecognized and undertreated. The impact of medical comorbidity may mask depressive symptoms. Social isolation, recent bereavement, and cognitive impairment as well as the stigma of depression and the belief that it is a normal part of aging, can also contribute to depression in the elderly.4-6 Untreated depression in older people impairs their quality of life and leads to a decreased ability for self-care, a decrease in social interaction, and an increase in health care use.7-9

Depression further complicates the prognosis of medical illness by increasing physical disability and decreasing motivation and adherence to prescribed medications and/or exercise or rehabilitation programs. These adverse associations apply to all types of depression in later life. In addition, older people make up about 12% of the US population but account for 16% of suicides. Chronic disabling disorders can be a contributing factor, but timely, appropriate treatment of depression can reduce this risk.10

This review provides an update of current evidence in relation to late-life depression and its diagnosis and treatment.

General etiological factors

The interaction between medical illness and depression in older patients is 2-way and self-perpetuating: physical illness increases susceptibility to depression and depression worsens medical outcomes. Lyness11 recently noted that depression and medical illnesses might have similar pathways that range from shared genetic vulnerabilities to the effects of personality or other enduring psychological or psychosocial constructs. The older patient’s own perception of his or her health plays a role in actual health: a poor perception is associated with increased depressive symptoms regardless of actual health impairment.3,5 A history of depression strongly predicts the development of depression after any major adverse health event.3

Many factors contribute to an increased risk of late-life depression. Sensory impairment and macular degeneration frequently affect older people and are also associated with high levels of depression.12 Physical disability is another strong predictor of late-life depression, although it may be modifiable: the patient who has poor transportation links and becomes isolated is at greater risk for depression.

Use of prescribed drugs and polypharmacy increases with age and can have an impact on depression. Drug-induced depression (along with depression caused by an occult illness, such as cancer, an endocrine disturbance, or early dementia) is an important differential diagnosis. A European study estimated the Population Attributable Risk percentage (PAR%)-depression associated with the use of certain medication-for a large number of medications.13 For nonselective b-blockers, the PAR% was 2.5%, for calcium antagonists it was 5%, and for benzodiazepines it was 15.42%.


Late-life depression is an umbrella term that covers a range of depressive symptoms from mild to severe in an older adult (usually defined as aged 65 years or older).4,7 The core symptoms are listed in Table 1. About half of late-life major depressive disorder (MDD) occurs in those with recurrent depressive disorder.4,7 It is harder to classify older individuals with disabling symptoms of depression who do not meet MDD criteria. The prevalence of this type of depression (variously labeled minor depression, subthreshold depression, or clinically relevant depressive symptomatology) exceeds that of MDD by a factor of 2 to –3. Therefore, the overall health burden is potentially as great or greater than for MDD.14

Somatic symptoms such as fatigue, sleep disturbance, decrease in social interaction, and loss of interest in pleasurable activities may be the result of physical illness, a depressive disorder, or both-especially in patients with physical comorbidity. Three symptoms may help with the diagnosis4:

• Depressed mood
• Mood worsening in the morning
• Hopelessness

In addition, when depressed, older people often minimize a complaint of sadness and instead become markedly hypochondriacal. Hypochondriasis is defined by DSM-IV and International Classification of Disease, Tenth Revision (ICD10) criteria in terms of disease conviction and disease phobia. DSM-IV states a “preoccupation with a fear of belief of having a serious disease based on the individual’s interpretation of physical signs of sensations as evidence of physical illness.”15 It can be difficult to disentangle symptoms due to hypochondriasis from those due to a physical illness.16 Sometimes this leads to overinvestigation, as with the depressed patient with the heart disease who develops noncardiac chest pain secondary to anxiety and repeatedly requests more tests. On other occasions, underlying illness may be obscured, as when an acutely depressed patient with a tension headache becomes convinced of a brain tumor whereas underlying occult gastrointestinal malignancy turns out to be the real problem.

Screening for depression in high-risk groups might improve detection. A number of validated and age-appropriate depression screening tools are available. One specifically for older people is the Geriatric Depression Scale (GDS) (Table 2).17 Because the GDS minimizes the number of somatic depressive items, there is no need to upwardly adjust the cut-off score.

The Patient Health Questionnaire 9 (PHQ-9) is a screening tool for depression in the primary care setting.18 A score of 10 or higher has a sensitivity of 88% and a specificity of 88% for major depression. It is a validated tool for telephone screening of depression in primary care, takes less than 5 minutes, and can be used to assess severity of depression.19


General principles

Effective treatment modalities are available for late-life depression, and successful treatment is associated with improved psychological and physical well-being, quality of life, social functioning, and possibly, reduced health care use and lower mortality. The principles of treatment are the same for all ages. The goals of treatment are outlined in Table 3.

Although the longer-term prognosis may be relatively uncertain, patients with medical comorbidity can respond just as well to antidepressants as physically healthy patients.20,21 Suicide risk can be reduced by timely treatment of depression and by reducing any likely means in high-risk patients. An example concerns the availability of firearms which are increasingly used by older men to commit suicide.22,23 Outcomes are improved by building a therapeutic relationship in which the patient receives adequate information about depression and in which misapprehensions about antidepressant therapy are addressed.

Depression is treated in 3 phases.

• The aim of the acute phase (usually the first 12 weeks) is to achieve remission (that is, no symptoms remain). Residual symptoms predict chronicity and relapse.
• In the continuation phase, prevention of return of symptoms (relapse) is the goal. Older patients with MDD commonly require up to 12 months of continuation treatment.
• The aim of the maintenance (prophylaxis) phase (generally beyond 12 months) is to prevent a new episode. SSRIs and some psychological therapies have been shown to work for up to 3 years in elderly patients with MDD.7

Nonpharmacological therapy

Psychotherapies, such as cognitive-behavioral therapy, behavioral therapies, reminiscence and life review, interpersonal psychotherapy, and problem solving, are as effective as antidepressants for patients with mild to moderate depression.24,25 Individual choice is important because there is evidence that physically unwell older patients with depression are likely to refuse antidepressant drug therapy because of fear of drugs.26 Treatments are usually provided over 6 to 12 weekly sessions and require only commonsense modifications for medically unwell patients (such as pacing sessions to avoid fatigue).

Increasingly, collaborative care models (CCM) are being used in the United States to treat late-life depression. CCM involves close collaboration between a case manager (usually a specialist mental health nurse or a clinical psychologist, either of whom deliver a brief psychological intervention), the local primary care physician, and a psychiatrist. CCM only works if there is regular and timely access to the psychiatrist who can offer advice about the most appropriate pharmacological treatment and next step treatments in patients who do not respond to initial management. CCM is effective in treating depressed patients with comorbid physical illness.27 Unutzer and colleagues28 investigated the longer-term cost effects of CCM for late-life depression in a 4-year follow-up study. Their findings confirm a previous 2-year follow-up indicating that CCM reduces health care use by older patients (including those with comorbidity) compared with usual care.

A recent systematic review suggests that physical exercise (walking or other aerobic exercise) may help reduce depressive symptoms in older people.29 Physical exercise may be considered as first-line treatment for older patients with mild depression.

Despite adverse publicity, electroconvulsive therapy (ECT) remains the most effective treatment for depression in older adults. Efficacy rates are as good as or better than those of younger adults.30 ECT is currently reserved for treatment-resistant depression or for those whose life or health is threatened by severe depression. However, ECT therapy should not be overlooked where available.31 A study of mixed-aged patients reported that virtually all patients experienced a relapse after ECT if not given ongoing medication.32 A combination of nortriptyline plus lithium offered the best protection.

Other treatments include deep brain stimulation and vagus nerve stimulation, but clearly these are highly specialized and reserved for patients with refractory depression.33 Still limited but more widely available is repetitive transcranial mag-netic stimulation, which is effective for moderate depression and possibly attractive for patients with medical comorbidity.34 However, there is a paucity of evidence for its use in later-life depression and the frequent treatment sessions may be problematic.

Pharmacological therapy

Antidepressants are as effective in older patients as in younger patients. There is no evidence that one class is more effective than another. However, tolerance and susceptibility to adverse effects may increase both with age and comorbidity. Vigilance over potential interactions with other drugs used to treat comorbidity is vital. Also, there is much more variability among older adults in pharmacodynamic responses to antidepressants. The same dose may have quite different effects on older persons of roughly the same age. Therefore, the adage “start low and go slow” is sensible when considering treatment options for older adults. It is also important to remember that antidepressants help in pain management.35

More than 20 antidepressants have been FDA-approved for the treatment of depression in older people (Table 4).7 SSRIs are the usual first-line choice of pharmacotherapy in older patients who are depressed because of lower serious adverse effect and toxicity profiles compared with older antidepressants.7 However, a risk of GI bleeding has to be considered in geriatric patients particularly if aspirin or NSAIDs are prescribed and/or there is a history of peptic ulcer; in such patients GI protection is advised. SSRIs are sometimes associated with a low sodium syndrome secondary to inappropriate secretion of antidiuretic hormone which, in extreme cases, leads to lethargy and confusion. In medically unwell patients, tricyclics increase the risk of delirium. Mirtazapine is useful when insomnia is problematic, and bupropion can be used for lethargic patients.

The chances of recovery are small if a patient has made no or minimal improvement after 4 weeks of treatment at optimal dose, in which case a change to another antidepressant is recommended.36 If the patient is improving, then augmentation strategies or antidepressant combinations are appropriate. Lithium and triiodo-thyronine may be used, and psychotherapy may also be effective.


The causes of depression are multifactorial. Several factors may contribute to depression, including sensory impairment, overall handicap, social deprivation, and individual coping strategies. There is every reason to be optimistic about treating depression in older adults. There are effective psychological and antidepressant drug treatments, for both the immediate management and to keep the patient well after recovery from depression. First, however, depression must be detected.

[Editor's note: The above article was published as a Category 1-CME in the November 2008 issue of Psychiatric Times (2008;25(13):50-54). The activity is now expired].


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