Definition

The term depression can have different meanings. It can be regarded as a “symptom” (low mood), a “syndrome” (a set of symptoms with various definitions), or as a medically defined diagnosis according to a classification system. Depressive symptoms can be viewed dimensionally, from more or less normal reactions to pathologically severe depressive symptoms. The symptoms occur on a continuum of severity from mild reactions to complete disablement. The classification systems have traditionally viewed depressive symptoms and depression categorically (Baldwin 2014).

There is no defined biomarker for depression; the diagnosis is based on a clinical interview, observation, and supplemental information from relatives and caregivers. A diagnosis of depression is made according to two main classification systems: the American Psychiatric Association’s Diagnostic and Statistical Manual, Fifth Edition (DSM-5), or the International Classification of Diseases, Tenth Revision (ICD-10). To fulfill the criteria for a diagnosis of a depressive episode in ICD-10, four depressive symptoms must be present. To fulfill the criteria for a major depressive disorder (MDD) in DSM-5, at least five depressive symptoms must be present. In both systems, the symptoms have to be present for at least 2 weeks, causing clinically important impairment in daily life function, and one (DSM-5) or two (ICD-10) of the symptoms should be among the core symptoms, which are depressed mood, loss of interest or pleasure (DSM-5 and ICD-10), or decreased energy (ICD-10). DSM-5 and ICD-10 comprise similar criteria but may differ in the identification of people fulfilling the criteria for depression (Table 1).

Depression in Later Life, Table 1 Diagnostic criteria of depression according to DSM-5 and ICD-10 (abbreviated)
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A substantial proportion of older persons can have clinically important depressive symptoms but not fulfill the DSM-5 or ICD-10 diagnostic criteria for depression. Only DSM-5 includes specific criteria for depressive episodes with insufficient symptoms, also termed minor depressive disorder or subsyndromal or subthreshold depression. Subthreshold depressive symptoms persisting for more than 2 years may be diagnosed as dysthymia in both classification systems. In DSM-5, persistent depressive disorder also includes persistent MDD. Finally, the DSM-5 and ICD-10 have specific criteria for bipolar depressive disorder, including different kinds of mania as part of the depressive disorder. It is important to keep in mind that DSM-5 and ICD-10 have been developed mainly in younger populations without cognitive impairment or substantial physical disease, and it has been argued that this makes the classification systems less valid in older people, particularly in the presence of cognitive impairment.

Depression in later life (DLL), also termed late-life depression or geriatric depression, is traditionally defined as depression occurring in persons older than 65 years, but other age cutoffs have been suggested, such as 60 years and even 55 years. Conversely, it has been suggested that the DLL should use a higher age cutoff than 65, because older people now experience better health and everyday function than they did in earlier times. Older persons can have DLL as part of a previously established mood disorder, or the depression can arise for the first time in late life. DLL is sometimes subdivided according to the age of the first lifetime depressive episode. Studies have used different age cutoffs (e.g., 50, 60, or 65 years) to distinguish between depression beginning in early life (early-onset depression [EOD]) and depression with the first manifestation in later life (late-onset depression [LOD]).

There is a complicated interplay between DLL and dementia. Some important issues are summarized in Table 2.

Depression in Later Life, Table 2 Depression and dementia
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Epidemiology

Depressive disorders are debilitating health problems and important causes of death for adults. Depression among adults across the life span is projected to be the leading cause of disability in middle and higher income countries by 2030. As the population of those aged 65 and over grows, DLL will become a major health problem worldwide. The prevalence estimates of DLL vary according to which diagnostic criteria have been applied, but overall the prevalence rates do not seem to be higher in older persons than they are in younger age groups. However, in subgroups of older persons, the prevalence rates are considerably higher. As in younger age groups, women are more likely to experience depression than men. Compared to the younger group of old adults, depression seems to be more common among the oldest old, often defined as 85+, as most studies find an increasing prevalence of depression with a higher age. However, the association between depression and increasing age seems to disappear when adjusting for physical disease and increased disability in older age. In community-based samples, the point prevalence of MDD in older people has been reported to be between 1 and 6%, but rates for subthreshold depression seem to be two to three times higher (Meeks et al. 2011). Higher prevalence rates of depression are found among old individuals in institutions, such as residential care or nursing home care facilities. Depression is also more prevalent in individuals with somatic disease, particularly brain disorders. Depression may occur in up to half of those who suffer from Parkinson’s disease or in those who have had a stroke. The prevalence estimates of depression in dementia are high but vary widely, reflecting the difficulty in defining and diagnosing depression in the context of dementia. To improve the diagnosis of depression in dementia, provisional diagnostic criteria for depression have been suggested, but their validity remains uncertain. Overall, depressive episodes in later life are more likely to be a recurrence rather than a first-time episode.

Etiology

Several biological, psychological, and social factors can interact and thus contribute to the development of depression. A biopsychosocial model of etiology seems to be particularly appropriate to DLL, highlighting that the causes of DLL are multiple and range across all three domains (Blazer 2003). It is useful to consider both predisposing and precipitating factors when putative causes of depression in an individual are assessed. There is still limited knowledge about why some older adults develop depression and others do not, even though they seem to be affected by the same set of risk factors.

Biological Factors

DLL regularly arises in the context of medical illness. There are several well-established physical risk factors like ischemic heart disease, chronic obstructive pulmonary disease, diabetes, malignancy, chronic pain, and organic brain diseases.

In addition, the use of drugs may play a central role in the development of depression in older adults. The role of alcohol is especially important to consider in the etiology of DLL given that the rates of alcohol consumption have risen among older adults, and it is well established that alcohol use is linked to lower mood and depression. Older individuals also use more medication more often than younger individuals, and it has been suggested that polypharmacy may be associated with the risk of depression. However, empirical evidence is not consistent, and the results are difficult to interpret because the condition for which the medication is taken often confers an increased risk of depression. Finally, substance dependence can also be a factor in the etiology of DLL and can be easily missed if not assessed in an older patient.

Brain Anatomy

Research indicates that certain areas or circuits of the brain are relevant to the etiology of DLL (Naismith et al. 2012). These areas include the dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, subcortical white matter, basal ganglia (especially striatum), and the hippocampus. Dysfunction in frontal-subcortical neural networks involving these areas seems to be associated with the onset and prognosis of DLL.

Neurotransmitter Dysfunction

The monoamines, namely, serotonin, noradrenaline, and dopamine, are important modulating neurotransmitters for mood and behavior. Dysfunction in serotonergic and noradrenergic neurotransmission and, to a lesser extent, dopaminergic transmission has been demonstrated in DLL (Thomas 2013). An association between abnormalities in these neurotransmitters and depression is also supported by the fact that antidepressant medication targeting serotonin and noradrenaline function improves depressive symptoms. Dysfunction in other neurotransmitters associated with the occurrence of depression includes gamma-aminobutyric acid (GABA) and glutamate. All of these neurotransmitters have widespread projections to the prefrontal cortex. Even though dysfunction of monoaminergic transmission is shown in DLL, it is not completely clear how aging affects the neurotransmitters. Some evidence suggests, however, that the age-related changes of the neurotransmitters can make older persons more vulnerable to mood disorders.

Genetics

Hereditary factors could predispose some older persons to depression. There has been great interest in genetic susceptibility across the life cycle, but specific genetic markers for DLL have not been identified. Heritability appears to be related to multiple loci of the genetic material (DNA) with small effects rather than few loci with large effects. Genetic factors have been found to have a greater impact in DLL with EOD. Recent genetic research has focused on the serotonin transporter (5HTTLPR) gene, apolipoprotein E (ApoE) gene, brain-derived neurotrophic factor (BDNF) gene, and 5-methylenetetrahydrofolate reductase (MTHFR) gene and has found that these genes may be involved in the development and treatment response of DLL (Naismith et al. 2012).

Immune System

Scientific knowledge regarding the interplay among the nervous, endocrine, and immune system has expanded immensely in recent years. It is suggested that these systems should be regarded as a single network that gives rise to the new discipline of psychoneuroimmunology (Thomas 2013). Research has shown that aging can lead to an increased peripheral immune response, impaired communication between the immune system in the central nervous system (CNS) and peripheral nervous system (PNS), and a shift toward a pro-inflammatory state of the immune system in the CNS. Raised levels of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, have been reported in studies of DLL. It is probable that aging and comorbid diseases may alter neuroinflammation and predispose individuals to DLL (Alexopoulos and Morimoto 2011).

Dysregulation of the HPA (hypothalamic-pituitary-adrenal) axis has been suggested as a cause of depression in older and younger adults. The associated high glucocorticoid levels may have a toxic effect on the brain, particularly the hippocampus. This has been forwarded as an explanation for the increased risk of dementia in people with depression, although findings linking high glucocorticoid levels with hippocampus atrophy are conflicting.

Vascular Disease

There is a well-established bidirectional association between vascular disease and depression. This includes coronary heart disease as well as cerebrovascular disease (i.e., stroke). The white matter of the brain is composed mainly by myelinated nerve fibers. Lesions to the white matter identified on MRI, or white matter hyperintensities (WMH), have been studied extensively in relation to depression. It is presumed that WMH are caused by chronic hypoperfusion of the white matter and the disruption of the blood–brain barrier. WMH are related to vascular risk factors, the risk of depressive episodes, poorer remission, and cognitive impairment. The strong relationship between cerebrovascular disease and depression has led to the “vascular depression” hypothesis, which postulates that cerebrovascular disease can predispose, precipitate, and perpetuate depressive syndromes in later life by damaging frontal-subcortical circuits (Alexopoulos 2005). However, the concept of a vascular depression has received some criticism and it has proved difficult to reliably identify such a subgroup. Nevertheless, vascular disease is likely to be an important factor in about 50% of people with DLL (Thomas 2013).

Psychosocial Factors and Personality

It is a common view that psychosocial factors are most important in mild to moderate depression, whereas biological factors play a greater role in severe depression. The scientific evidence for this view is rather limited, and the evaluation of possible psychosocial etiological factors should be part of the assessment regardless of the severity of depression.

Several psychological factors are associated with depression. Relatively little research on the association between personality and depression has been done, and the interpretation of the results is difficult. Most studies are cross-sectional or retrospective, and the recall of earlier personality traits may be influenced by the present situation. It is also difficult to establish what came first, the depressive disease or the presumed personality trait. Furthermore, it is complicated to disentangle the contribution of the personality traits from the social situation of the person as risk factors for depression.

There is some evidence that a high level of neuroticism is linked to DLL. Neuroticism is a personality trait characterized by worry, fear, anxiety, guilt, and moodiness. People with a high level of neuroticism can be sensitive to life stressors and may interpret minor situations as threatening or hopelessly difficult. It has been suggested that older persons with depressive syndromes can display cognitive distortions, where they generally overrate their own mistakes and exaggerate negative outcomes of life events and where loss and defeat are core themes.

High levels of mastery of one’s environment and self-efficacy have been shown to provide protection against DLL. A higher sense of control, an internal locus of control, and more active strategies have been found to be associated with fewer depressive symptoms (Bjorklof et al. 2013).

Learned helplessness is the idea that individuals behave according to the expectation that acting in continually stressful situations has no meaning. Older adults frequently encounter circumstances such as chronic physical illness and disability that may lead to learned helplessness, and this notion has been linked to the occurrence of DLL (Aziz and Steffens 2013).

Life Events

Stressful life events can be seen as an integral part of becoming old, but some types of stressful life events, such as divorce or criminality, are less common in old age. It could also be argued that stressful life events are more often expected in late life, making it easier to deal with them.

As a person grows older, he or she will inevitably deal with different types of loss. For example, these losses include loss of position in society, loss of a job, loss of financial and functional independence, and loss of a social network and loved ones. These losses may produce grief that develops into depression.

Social support may act as a buffer to stressful life events, and it is documented that impaired social support is related to DLL. However, it is important to bear in mind that the majority of people who experience significant losses in old age do not develop depression. Hence, the meaning of loss has to be interpreted in the context of the person’s mastery style, social situation, and other predisposing factors (Aziz and Steffens 2013).

Clinical Picture

Several studies have shown that clinicians at various levels fail to recognize depression in older persons. There may be a tendency to attribute depressive symptoms to the normal aging process. This may also explain the reluctance of some old people to view their symptoms as signs of depression. It is important to stress the fact that depressive symptoms are not a consequence of normal aging. The most plausible reason for the low detection levels of depression is probably the rather complicated interplay between normal age-related changes, symptoms of somatic disorders and depressive symptoms. This may cause clinicians to miss the diagnosis or also hinder insight by the person with depressive symptoms.

The ICD-10 criteria for depressive episode and DSM-5 criteria for MDD are identical for both younger and older patients (Table 1). The core symptoms of depression are depressed mood, loss of interest or pleasure, and decreased energy (the latter only in ICD-10). Additional symptoms defined in the diagnostic criteria are loss of confidence, an excessive feeling of guilt or worthlessness, difficulty concentrating, change in psychomotor activity, disturbance of sleep, change in appetite with corresponding weight change, and suicidality.

The clinical presentation of depression in old people differs from what is seen in younger age groups. The aging process, cognitive impairment, reduced physical health, polypharmacy, and disability can contribute to a more heterogeneous presentation of a depression syndrome in older individuals. Older adults may be less likely to describe their suffering in ways that match up to common depressive symptoms. For instance, older persons with frank depression rarely describe experiencing feelings of sadness. This has led to the term “depression without sadness.” More recent research, however, has challenged the view that there is a specific phenotype in depression among old people, suggesting that the key symptoms of depression are the same, irrespective of age (Thomas 2013).

However, it seems that some symptoms are more prominent in DLL, with cognitive impairment being the most important. Various expressions have been used to describe cognitive impairment in depression, with pseudodementia being the most common. Pseudodementia refers to depression that is misdiagnosed as dementia due to marked symptoms of cognitive impairment. This term has fallen out of use, however, given the persistent nature of cognitive deficits in depression, even after the depression has been successfully treated and recent evidence suggesting that depression is a risk factor for dementia (Butters et al. 2008). The characteristic pattern of cognitive impairment in depression includes impaired attention and executive and amnestic impairment, whereas apraxia, visuospatial impairment, and aphasia may indicate that the cognitive impairment stems from a comorbid dementia disorder. People with a substantial cognitive impairment as part of their depressive episode should be followed-up closely, even if the cognitive impairment is reversed after the treatment of depression, because the risk of developing dementia in the following year is higher in this group.

Other patterns of the symptom profile in DLL are somatization or hypochondriasis, psychomotor retardation, anxiety, and agitation. It should be noted that some of these symptoms are also common in other diseases that frequently occur in old age, such as chronic obstructive pulmonary disease and coronary heart disease.

Psychotic symptoms seem to be more common in DLL compared to depression in younger adults.

There is evidence that for many patients with dementia, the depression syndrome may differ from the diagnostic criteria in the ICD-10 and the DSM-5. Thus, provisional criteria for depression in patients with Alzheimer’s disease have been suggested. These criteria require fewer symptoms for a diagnosis of depression and the symptoms do not have to be present nearly every day. In addition to the depressive symptoms described in ICD-10 and DSM-5, the criteria for depression in Alzheimer’s disease also include social withdrawal or isolation and irritability (Olin et al. 2002).

Assessment of Depression

In addition to a thorough disease history that considers biological and psychosocial risk factors, the use of a structured assessment scale for depression is recommended. A few scales have been developed for use in old people, such as the Geriatric Depression Scale (GDS) and the Cornell Scale for Depression in Dementia (CSDD); the latter is also used in people without dementia. Other well-known scales, such as the Montgomery-Åsberg Depression Rating Scale (MADRS), the Hamilton Depression Rating Scale (HAM-D), the Beck Depression Inventory (BDI), the Patient Health Questionnaire (PHQ), and the Hospital Anxiety and Depression Rating Scale (HADS), are frequently used, and the psychometric properties of most of these scales are found to be acceptable in the assessment of DLL. Reporting depressive symptoms may be hampered by cognitive impairment and the assessment may have to include a proxy-based assessment, such as the CSDD. Given the large proportion of people with DLL who experience impaired cognition, a structured assessment of cognition should be included in the diagnostic process, whether or not a dementia disorder is suspected.

Suicidality

The suicide rates in older adults, particularly in men, have risen. Older men have few suicide attempts per completed suicide, i.e., they choose more lethal methods. An assessment of suicidality should be part of all assessments of DLL. As with any patient population, the older patient must be approached sensitively. Nevertheless, an explicit and specific exploration of suicidal thoughts should be carried out during the assessment. Older men who commit suicide often seek medical help prior to the attempt, but symptoms of depression or suicidal thoughts are rarely mentioned. Practitioners need to be aware of this and have suicidality in mind when older men seek advice about other conditions, particularly issues concerning pain management. Established risk factors for suicide among old people are bereavement, social isolation, earlier attempts, chronic painful illness, disability or the threat of increasing disability, drug or alcohol use, and sleep problems (Manthorpe and Iliffe 2010). Despite the concern about the high rate of suicide among old people, this issue has received little attention, particularly when compared to the attention toward suicidality in younger people. Practice guidance on how to reduce the risk is lacking, and intervention studies are scarce.

LOD and EOD

Some researchers suggest etiological and clinical differences between EOD and LOD. EOD is associated more with a family history of depression, personality dysfunction, and severe disorders. EOD is regarded as a risk factor for the later development of dementia. LOD is associated more with WMH on MRI, prominent cognitive impairment, and it relates more to systemic vascular risk and neurodegenerative disorders. There is a debate as to whether the symptom profile of depressive symptoms defined in the classification systems is different in EOD and LOD patients.

Bipolar Disorders in the Late Life

The number of people seeking care for bipolar disorders is increasing. Bipolar disorders can develop early, i.e., onset before 50 years of age, or can arise with a late onset, i.e., after 50 (different cutoffs between 50 and 65 have been used). Bipolar disorders in late life include both early and late onset. Due to the complexity and heterogeneity in the classification of the disease, prevalence rates vary. Among older patients with bipolar disorder, most have their first episode of mania or depression early in life; in the minority, a bipolar disorder may present itself for the first time in old age. In that case, the diagnostic process may be challenging due to the extensive medical comorbidity. Medical comorbidity in bipolar illness is associated with a more disabling course of the illness and a higher risk of suicide (Sajatovic and Chen 2011). Psychiatric comorbidity, such as anxiety disorders or substance use disorders, is often less common among older people than younger people with bipolar disorder. Patients with a late onset of bipolar disease tend to have less history of mood disorders in their family. About half of all older patients with bipolar disorder have depression as their first mood episode.

Treatment

Before starting treatment, a careful assessment focusing on the biopsychosocial aspects of DLL is needed. The assessment should not be restricted to counting symptoms in order to establish a diagnosis; the meaning or the impact of the depressive symptoms to the individual person needs to be taken into account. Functional limitations and disability, disease history, and the duration of symptoms are key issues to keep in mind when weighing the benefits of treatment against risks. Earlier treatment experiences and preferences of the patient should be taken into account. A careful explanation of the treatment plan involving the patient – and if appropriate a family caregiver – is mandatory for treatment success, as low treatment adherence has been reported among old people.

A stepped care approach, identifying the least restrictive and least costly intervention that will be effective for a person’s presenting problems, is recommended (NICE 2010). People with subthreshold depression without a significant impact on everyday life should be offered supportive and psychosocial interventions, but they should normally not be offered medical treatment. In milder forms of depression or persistent subthreshold depression, more intensive psychotherapeutic approaches are advocated. Drug treatment should still not be a first-line treatment option, but should be considered if other alternatives fail to produce substantial improvement. In moderate or severe depression, drug treatment should be offered, often in combination with intensive psychotherapeutic treatment.

In the treatment of depression, it is important to aim for remission (i.e., patients do not meet the diagnostic criteria for depression or they have no more than minimal depressive symptoms according to a depression assessment scale) and not merely for response (i.e., significant symptom reduction), because residual symptoms after treatment are strongly associated with a risk for relapse. Once in remission, a plan for the continuation of treatment should be established. There is reason to believe that maintenance therapy should be offered more liberally in DLL than in younger age groups, due to a greater risk of relapse.

Psychosocial Interventions

Older patients with minor or mild depression can benefit from participating in various types of social activities to prevent isolation and loneliness, e.g., befriending services and attending day centers and local community events. Physical exercise includes bodily activity that enhances overall health and wellness. There is evidence that structured exercise programs can help older patients with milder depressive syndromes. Different kinds of exercises can be beneficial, but results are most consistent from aerobic exercise. However, there are also studies that have failed to find a positive effect of physical exercise in DLL.

Psychotherapy

Research indicates that psychotherapy can be an effective treatment for DLL even though the quality of studies is relatively low (Wilson et al. 2008). There is a variety of therapies that may be applied, such as supportive therapy, life-review therapy, cognitive-behavioral therapy (CBT), interpersonal therapy (IPT), and problem-solving therapy (PST). Psychotherapy can be offered to individuals (in- or outpatients), couples, families, and as group therapy. Supportive treatment and adding structure to the day can be effective in patients with minor depression syndromes. CBT focuses on here-and-now situations as well as the link between negative thought patterns and mood and behavior and is often structured in sessions and length. CBT is widely studied and applied in DLL with mild to moderate severity. IPT is also based on here-and-now situations, but emphasizes interpersonal relationships. PST is based on CBT principles, but is a more focused treatment approach. PST aims to teach patients to better define their problems and goal, and the strategies to cope with the problems, carry out the strategies, and then evaluate them. PST has shown strong results for depressed patients with executive dysfunctions. As a result, it has been suggested as a key treatment approach in “vascular depression,” where it has been implicated that the dysfunction of frontostriatal circuits gives rise to executive impairment (Espinoza et al. 2014).

Psychotherapy, in combination with medical treatment, may be more efficacious than any of the two modalities alone in the treatment of DLL, both in the acute phase and as maintenance therapy.

Medication

A number of issues need consideration when prescribing antidepressive medication to older adults. As noted earlier, polypharmacy is common in older individuals. Medication with negligible side effects in healthy young people may cause serious side effects in older adults who take many prescribed drugs, especially when several of those drugs could have direct effects on the brain. An example is the rather weak anticholinergic effect of a drug like paroxetine; in combination with other drugs with weak anticholinergic effects, it may cause confusion or delirium in susceptible individuals. Pharmacokinetic changes, such as increased distribution volume, reduced hepatic metabolism, and reduced glomerular filtration rates, may lead to higher plasma and brain levels of the drug. However, there is great variation among older adults in these changes. The slogan “start low, go slow” that was often voiced in old-age psychiatry may be appropriate, but should not prevent older patients from being treated with adequate doses. When evaluating dosing regimens, the polymorphisms of key enzymes of the cytochrome P450 system involved in the metabolism of several psychopharmacological substances should be taken into account. A considerable proportion of individuals can have polymorphisms that may cause great variation in the plasma level of a medication. In cases of unusual side effects at low doses or treatment resistance, an analysis of P450 enzymes may be indicated.

Most studies regarding drug treatments for depression have been done in samples with MDD. Hence, the results cannot readily be extrapolated to people with mild depression or subthreshold depression. The effect of antidepressants in treating DLL is well documented (Nelson et al. 2008). However, there is great variability among studies. The older tricyclic antidepressants (TCAs) have a comparable effect to the new ones but a higher prevalence of side effects – particularly anticholinergic and antiadrenergic effects – that have made them less useful in treating DLL.

Contrary to the positive treatment effect in older adults without substantial cognitive impairment, most of the studies concerning the use of antidepressive treatment in patients with dementia have failed to show an effect (Nelson and Devanand 2011). This may be because of an inability to define homogenous patient groups with depression and dementia. Symptoms of depression and dementia partially overlap and cognitive impairment may prevent any verbalization of the depressive symptoms. Furthermore, people with dementia may be more susceptible to adverse events. Taken together, there is not enough evidence to suggest antidepressive therapy as a first-line treatment in people with dementia except in specific cases, such as very severe depressive symptoms or a history of earlier episodes that have responded to treatment.

There are a large number of antidepressive drugs to choose from, but selective serotonin reuptake inhibitors (SSRIs) are the first choice in most instances, in line with most clinical guidelines. These drugs are generally well tolerated and they have a predictable interaction profile. Nonetheless, recent studies indicate that SSRIs may also be associated with serious adverse outcomes, such as increased QT interval, falls, and hyponatremia. SSRIs may be combined with other antidepressants; combining SSRIs with mirtazapine or mianserin can be particularly useful for patients with sleeping problems and low appetite. Serotonin and noradrenaline reuptake inhibitors (SNRIs) have adverse event profiles similar to SSRIs and are a useful second-line treatment option because of their somewhat broader receptor profile. Because older adults with depression constitute a heterogeneous group, the prescription of antidepressive medication should be individualized based on the side effect profile of the drug, previous medication history, somatic diseases, and the use of other drugs.

Monotherapy is preferred, but in cases of treatment resistance, augmentation therapy with other drugs may be tried. The best evidence is for augmentation with lithium, used for bipolar disorder (Cooper et al. 2011). However, lithium serum levels have a very narrow therapeutic window and require careful observation in order to avoid potentially serious adverse events.

Electroconvulsive and Neuromodulation Therapies

Electroconvulsive therapy (ECT) is well tolerated and efficacious in treating DLL (Riva-Posse et al. 2013). It should be an option in people with severe depression when other treatment alternatives have failed. In many countries, ECT is reserved for severe depression with psychosis, suicide risk, or life-threatening refusal of food or fluids. Concerns about using ECT in DLL have been raised, especially the fear of precipitating delirium or memory impairment. Recent studies demonstrate a faster remission in patients treated with ECT than patients treated with antidepressants, without extra side effects. This suggests that the indication for ECT could be broader. The high relapse rate after ECT is a therapeutic challenge; maintenance therapy may be indicated. Other stimulation therapies, such as transcranial magnetic stimulation, vagal stimulation, or deep brain stimulation, have been tried out in selected patient groups, but these alternatives are not easily accessible and there is limited evidence to date to justify their use in clinical practice.

Prognosis

DLL is associated with a number of negative outcomes, such as disability, cognitive impairment, poorer outcomes of physical disorders, and an increased risk of mortality. Remission rates of DLL after treatment are not different from those in younger age groups; however, relapse rates are higher (Mitchell and Subramaniam 2005). The risk of relapse is highest for the first 6 months. Hence, it is important to continue treatment for at least 6–9 months. Even after the first depressive episode in old age, the relapse rate is high after the treatment has been discontinued. This has led many to recommend lifelong maintenance treatment even if the first depressive episode has a later onset, particularly if it was an episode of great severity. This recommendation has to be weighed against risks associated with polypharmacy, side effects, and other risk factors for relapse, such as cerebrovascular pathology, other physical diseases, and cognitive impairment.

Conclusion

DLL is a disease with vast consequences for affected individuals and society as a whole. The symptoms are well characterized and there is a huge knowledge base around epidemiology, etiology, and treatment. However, a substantial part of the knowledge relates to younger age groups, which has been extrapolated to DLL. There is reason to believe that there are important etiological and clinical issues that apply to DLL, which differ from what we see in younger age groups. Yet, there is probably greater diversity among older versus younger age groups. This calls for a careful assessment and consideration of biological and psychosocial issues common with advancing age. Particular attention should be paid to comorbid physical diseases, cognitive impairment, and distressing life events. The increased vulnerability of some older adults to depression in itself and treatment side effects, the uncertain efficacy of treatment in subgroups, and the high relapse rate in DLL call for close follow-up. Lastly, the high risk of suicide, particularly in older men, warrants special attention among all health workers providing care for older individuals.

Cross-References