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Maju Mathews, MD, DPM, MRCPsych, Manu Mathews, MD,
and Joanne Mathews, MD

Primary Psychiatry. 2004;11(2):33-37

Focus Points

Depression is a common but underdiagnosed and undertreated condition among older persons.

Late-life depression is associated with cognitive impairment, physical illness, disability, and increased mortality.

Issues like bereavement, loneliness, and physical health assume a more important role in the treatment of depression in older people, compared to younger adults.

Various interventions, including pharmacotherapy, psychotherapy, electroconvulsive therapy, and social support are useful in the treatment of depression.


Depression in older persons is not the same disorder that afflicts younger persons. In fact, late-life depression is a major public health concern that is underdiagnosed and undertreated. It results in unnecessary suffering for the affected individual and is associated with excess mortality rates among depressed older adults. This article reviews the current literature on this common and multifaceted condition and examines various concepts of late-life depression, its diagnosis, and treatment options.


Depressive symptoms are common among older persons, affecting approximately 10% to 15% of the older population.1,2 Among people who seek health care for other medical problems, the prevalence of depression may be as high as 50%,3 and it is ≤47% among people living in sheltered accommodation and nursing homes.4,5 Thus, late-onset depression is a major public health concern, not only because of inflicted personal suffering, but also because of its related morbidity and excess mortality.6-8 Unfortunately, depression in late life is underdiagnosed and undertreated3,4,9 and its significance is underestimated, despite evidence that it is associated with disproportionately high rates of suicide and mortality.

Diagnosis of Depression

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition10 criteria for depression are shown in Table 1. These criteria can be used for the treatment of older persons as well as younger adults. When examining criteria, the number of symptoms and their chronicity are the two most important clues as to whether depression is major or minor, or as to whether the patient has dysthymia, an adjustment reaction, or a brief depressive reaction.

Screening instruments may have a role in detecting depression in the geriatric population; the most commonly used is the 15-item Geriatric Depression Scale (GDS) (Table 2).11 A cutoff score of 5 on the GDS gives a sensitivity of 92% and a specificity of 81%.12 It performs satisfactorily in patients with mild to moderate dementia but not severe dementia. A shorter 4-item scale also exists, and this form has been shown to be comparable to the longer GDS (Table 3).13,14 Actually, the diagnostic values of the 30-item, 15-item, 10-item, and 4-item versions do not differ significantly. The GDS is unique in that it focuses almost entirely on the cognitive aspects of depression rather than on the physical depressive symptoms and has a simple yes/no answer format. This is particularly useful, considering the fact that many of the patients in this age group have multiple physical illnesses.



Other rating scales that may be used in geriatric depression include the Cornell Scale for Depression in Dementia,15 Center for Epidemiological Studies-Depression Scale,16 Beck Depression Inventory-II,17 Hamilton Rating Scale for Depression, and the Even Briefer Assessment Scale for Depression.18

When diagnosing for late-life depression, it is appropriate to investigate past psychiatric history, medical history, and collateral information from caregivers. In those with significant depressive symptoms, the following should also be considered: a mental status examination, which should include testing for psychotic symptoms and cognition; risk assessment for harm and self-neglect; laboratory investigations including complete blood cell count, biochemical profile, B12, folate, and thyroid function tests; and a review of medications for agents that may exacerbate depression.

The differential diagnosis for late-life depression includes physical illness (eg, neoplasms, anemia, infections, and thyroid disorders), dementia, delirium, and delirium superimposed on dementia. It may also include focal cerebral syndromes, anxiety disorders, late-onset schizophrenia, parkinsonism, personality disorders, and bereavement.

Concepts of Late-Life Depression

The main difference between early- and late-onset depression is postulated to be causative. Whereas heredity appears to play an important role in early-onset depression, age-related vascular changes are presumed to be common causes of late-life depression. Actually, late-onset depression is probably due to several varying underlying causes, rather than a separate disease entity.19 For example, psychosocial vulnerabilities like poverty, lack of support from family, chronic illnesses, and isolation can increase the risk of depression. These can magnify the impact of even mild stress and coping mechanisms.20,21

Brain abnormalities in the form of deep white-matter hyperintensities are also associated with a greater number of depressive symptoms in normal older volunteers. This association is especially strong in individuals with the apolipoprotein e4 allele.22 The most prominent depressive symptoms in patients with subcortical white-matter hyperintensities are impaired motivation, concentration, and decision making. This may indicate that striatofrontal dysfunction caused by white-matter hyperintensities is an important contribution to the symptomatology of late-life depression.23 Cerebral vascular changes, and basal ganglia lesions in particular, are also associated with geriatric depression.

Depression and Cognitive Impairment

Depression is commonly associated with cognitive impairment. In patients with vascular dementia, the prevalence of depressive symptoms is high (31.4%), as it is among those with Alzheimer’s dementia (19.8%), compared to cognitively normal elderly persons (13.2%). This is presumably because depression may be a psychological reaction to eroding cognitive abilities; because depression and cognitive decline may be the result of a common underlying central nervous system disorder; or because high cortisol levels associated with depression may lead to neuronal death and dysregulation of the hypothalamic-pituitary-adrenal axis, thereby causing hippocampal atrophy and cognitive decline.

When the clinician evaluates patients with such cognitive impairments, information from a collateral source is necessary, as failing memory, poor insight, and word-finding difficulties may prevent patients with dementia from reporting depressive symptoms. Screening instruments available at present are not designed to detect depression in less verbal, more cognitively-impaired populations—such tests are more useful in the early stages of dementia, where depressive symptoms are more common.24

Furthermore, older individuals with major depression perform poorly on cognitive tasks that make demands on executive functions. These include operations such as selective attention, inhibition of irrelevant information, strategic planning, and abstraction. This poor performance is viewed as evidence of executive dysfunction arising from frontostriatal pathophysiology. However, the cognitive decline associated with depression (ie, pseudodementia) usually responds to the treatment of depression, though it may be associated with residual deficits.There is also an association between depressive symptoms and subsequent decline in speed of information processing. This may be further support that depression and cognitive slowing have a common underlying organic pathology of cerebral subcortical white-matter lesions.25,26

Depression and Disability

Depression is associated with disability, though most disabled people are not depressed. Rather, poor health, loss of mobility, and depression are linked with loneliness and social isolation. Subjective measures of ill health are strongly related to depression. Loss of function has a worsening effect on depressive symptoms, which in turn has a negative effect on functional ability.27 Disability may also be associated with impairment in initiation and perseveration and with late-onset depression.28


Suicide among older depressed individuals is multifaceted; it is a result of the complex interaction between medical, psychological, and sociocultural factors. Suicide rates increase with age and are highest among Americans ≥65 years of age. The largest relative increase in suicide rates in the United States occurred among those 80–84 years of age. Suicide rates are also higher for men: among those ≥65 years of age, men accounted for 84% of suicides in 2000. Rates can be extremely high for those divorced or widowed as well.29

The reasons for increased risk among older adults are that older people have a higher prevalence of depression, are more socially isolated, and often use more lethal methods. They make fewer attempts per completed suicide, have a higher male-to-female ratio, have visited a healthcare provider before their suicide, and have a greater prevalence of physical illness.29

Important indicators of risk for suicide include spontaneously reported wishes to die and suicidal ideation. Elderly patients reporting suicidal thoughts and feelings present with markedly high levels of physical and psychological suffering, and may be likely to complete an attempt.30

Late-life depression is also associated with increased mortality from medical illness. Cardiovascular diseases6,31-33 and stroke34 are common causes of mortality in depressed older adults. Several possible mechanisms have been proposed for this increased mortality, including comorbid physical illness, occult illnesses (eg, carcinoma), illness effects, treatment effects, biological effects such as abnormality of the hypothalamic-pituitary-axis, or endocrine abnormalities that affect the immune system.35


Treatment of depression in the elderly is an interdisciplinary process that must recognize psychological, social, and pharmacologic determinants. Pharmacologic therapy is useful for treatment, though there are a number of considerations that need to be borne in mind before starting it: with advancing age, there are important changes in the distribution, metabolism, and elimination of drugs. The age-related increase in the volume of distribution results in a longer half-life for most psychotropic medications and hepatic drug metabolism decreases with age, which results in a prolonged half-life as well. Decrease in renal function may also affect levels of drugs like lithium.36

As a result, it is necessary to use a medication with a low adverse-effect profile. Elderly patients with depression may be successfully treated with tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), atypical antidepressants, and mood stabilizers. TCAs have the major limitations of anticholinergic effects, postural hypotension, excess daytime sedation, and cardiotoxicity in overdose. However, they are efficacious and cheap. The secondary amines like desipramine and nortryptiline have the most favorable side-effect profiles. Other TCAs like amitryptiline may be associated with more side effects.37,38

Among MAOIs, phenelzine has been shown to be effective in treating older patients who cannot tolerate TCAs, and in treating those with resistant depression. However, MAOIs can cause hypertensive crisis with tyramine-rich foods.39

The advantages of SSRIs over TCAs include the absence of anticholinergic side effects, orthostatic hypotension, and arrhythmia, and the fact that they are not as detrimental when overdosed. The consensus statement update from the US National Institute of Mental Health (NIMH) on the diagnosis and treatment of depression in late life concluded that SSRIs are roughly equal to TCAs in efficacy among older persons, with 60% to 80% responding to treatment.40

The expert consensus guidelines for the pharmacotherapy of older patients found the SSRIs citalopram and sertraline to be acceptable as effective and well-tolerated first-line agents. Paroxetine was also suggested as a first-line medication, with fluoxetine as a high second-line agent.40 Fluoxetine has a half-life of >1 day, which can be advantageous when weaning a patient off therapy, because it reduces the incidence of discontinuation symptoms. However, this half-life can be a disadvantage if the patient cannot tolerate the drug and it has to be discontinued.

In a comparison of fluoxetine and nortryptiline in patients with severe depression and heart disease, nortryptiline was shown to be more effective. A meta-analysis of the comparative efficacy and safety of SSRIs and TCAs in older patients showed no differences in safety and dropout rates.41

Side effects of SSRIs include nausea, diarrhea, insomnia, headaches, agitation, anxiety, sexual dysfunction, and worsening of parkinsonism. They may also cause hyponatremia, hypomania, and seizures.

Other medications that may be useful in treating geriatric depression include trazodone, venlafaxine, mood stabilizers, and electroconvulsive therapy (ECT). Trazodone may be a drug of first choice for patients in whom anxiety and insomnia are problematic and in those patients who cannot tolerate, or are unresponsive to, therapy with other agents. Venlafaxine inhibits the reuptake of serotonin and norepinephrine. It has been shown to be more effective than placebo in relieving depression. However, it can cause hypertension and hyponatremia.42,43 Mood stabilizers are widely used for preventing and treating recurrences of depression. The most commonly used are lithium, carbamazepine, and valproate.

ECT can be very effective among older patients with depression with psychotic features, though usually these patients respond better to a combination of antidepressants and antipsychotics (the remission rate among combination treatment completers has been shown to be as high as 95%).44 However, the elderly represent a growing segment of patients treated with ECT. Many of these older patients suffer from concurrent medical illness, which precludes adequate trials of pharmacotherapy. The efficacy of ECT in geriatric depression is well established and perceived to be superior to that in younger age groups.

Anxiety and agitation in older persons may be predictors of good response to ECT, in contrast to young adults.45 Patients >65 years of age have been shown to have response rates as high as 90%, in contrast to rates of 75% seen in patients <45 years of age. Geriatric patients who responded to ECT exhibited a higher incidence of psychotic features, older age of onset of depression, and lower number of previous episodes than younger adults with depression.46 The severity of subcortical gray-matter hyperintensities may predict a poorer response to ECT.47

Continuation and Prophylactic Treatment

Continuation treatment with antidepressants has been shown to prevent relapse. In particular, nortryptiline with or without interpersonal therapy (IPT) has been shown to be effective in maintaining remission. Generally, though, good outcomes can be obtained by the use of a full dose of antidepressant medication, frequent follow-ups, and rigorous treatment of relapse.48

The NIMH consensus update recommends the continuation of treatment for  ≥6 months for those with first onset in late life, and ≥12 months for those with recurrent illness. Prophylactic treatment should be of the same type and at the same dose as the treatment that was effective in the initial acute phase. The treatment response and long-term outcomes are similar to those observed in younger patients but the temporal course is slower and the risk of relapse greater.

Lithium may be used in recurrent depression with melancholia and delusional depression. The advantage to using lithium is decreased mortality from suicide.49,50

Treatment Resistance

Treatment resistance can occur in up to a third of patients. It is related to cognitive impairment, physical and psychiatric morbidity, late onset, and presence of melancholic and psychotic features. For patients with treatment resistance, the following questions should be considered: Is the diagnosis correct? Are there comorbid conditions? Is the patient on the correct medication? Is the dose adequate? Has it been tried for a reasonable duration (4–6 weeks)?

Combination and augmentation strategies for treatment-resistant patients include lithium with TCAs, lithium with SSRIs, TCAs with triiodothyronine, SSRIs with TCAs, SSRIs with anticonvulsants, and SSRIs with estrogens. Patients receiving adjunctive medication may need continuation to remain healthy and to avoid early relapse.51,52 ECT may also be used in treatment-resistant depression.

Psychological Therapies

The efficacy of cognitive-behavioral therapy is well established for younger adults; however, though it is effective in the elderly, it is utilized less, as longer periods of treatment are required.53 For successful therapy, there should be an explanation of rationale, setting of realistic goals, reinforcement, group work, involvement of significant other, gradual termination of therapy, and use of follow-up sessions.54 The use of supportive therapy, problem-solving therapy, and IPT may also be useful. Finally, social interventions in the form of caregiver support, family counseling, visiting nurse services, and social support55 have been shown to be useful.


Depression among older persons is associated with good response to treatment. Most patients recover with appropriate treatment. The outcome for older depressed patients can be as good or better than for younger patients with depression.56,57

Future Directions

It has been proposed that the dopamine D3 receptor of striatofrontal dopaminergic enervation should be a target for further study because executive dysfunction may be mediated by the dopaminergic system. Acetylcholine and opiates also modify neurotransmission in these pathways and are worthy of study.58 Nimodipine, a calcium channel blocker, has been used in the treatment of vascular depression with some effect.59 Behavioral activities to reduce depression, such as structured activities and prompts to initiate behavior, might also be helpful. There is a need for better trials of antidepressants and psychotherapies and also an understanding of vascular elements in the etiology of depression.


Given its high prevalence and its inadequate recognition, the greatest challenge facing clinicians caring for the elderly is the recognition and treatment of late-life depression. This requires a greater understanding of depression among primary care physicians and internists, as these are the professionals dealing most frequently with this population. Education of staff working in assisted living facilities and nursing homes is also important. The use of a short questionnaire like the 4-item GDS can identify substantial numbers of patients, who can then be referred for further evaluation and management. PP


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Dr. Maju Mathews is resident at Drexel University College of Medicine in Philadelphia, Pennsylvania.

Dr. Manu Mathews is staff psychiatrist at East Surrey Hospital in Redhill, Surrey, United Kingdom.

Dr. Joanne Mathews is resident at Drexel University College of Medicine.

Disclosure: The authors report no financial, academic, or other support of this work.

Please direct all correspondence to: Maju Mathews, MD, DPM, MRCPsych, Eastern Pennsylvania Psychiatric Institute, 3200 Henry Ave, Philadelphia, PA 19129; Tel: 215-842-6000; Fax: 215-842-7635; E-mail: