Screening, diagnosis and treatment

In the elderly, depression is even more frequently overlooked than in younger people, since depressive symptoms such as hopelessness and joylessness, sleep disturbances or feelings of exhaustion are often not seen as an expression of an independent serious illness, but are misinterpreted as an understandable consequence of the bitterness of old age or an expression of physical comorbidities. In this context, frequent comorbidities and concomitant medications make treatment more difficult, but no less important because of the increased risk of suicide in old age.

Even though the incidence of neurodegenerative diseases increases massively with age, depression remains the most common mental illness in people over 65. Because many older persons present with depressive symptoms that do not correspond to the severity of a depressive episode, a distinction is usually made between depressive episode and subsyndromal depression [1]. One study showed a point prevalence of approximately 7% for a depressive episode and a prevalence of 17% for clinically relevant depressive symptoms in people over 75 years of age [2]. According to the studies, the prevalence is likely to be even higher, especially among people living in institutions. For example, the prevalence of mild depression has been shown to increase to 31% in those over 75 years of age, compared to approximately 14% in younger individuals. Accordingly, subsyndromal depressive states are more common in old age than in younger cohorts due to age-specific psychosocial circumstances, such as loss of strong attachments [3].

Increased risk of suicide in old age

A distinctive feature of depression in the elderly is the high risk of suicide, especially in socially isolated men with chronic somatic comorbidities. Overall, the risk of suicide is about 20 times higher in older men than in young women. Depression is thus the greatest risk factor for suicide in old age. Approximately 55-80% of individuals who committed suicide suffered from a depressive episode during the period of the suicide. Furthermore, in contrast to younger persons, the outcome of a suicide attempt in older persons is more often fatal, since so-called hard suicide methods, such as hanging, strangulation, or use of firearms, are used more frequently in old age than drug intoxications.

Suicide exploration includes eliciting factors that are more likely to protect against suicide such as values, beliefs, presence of children, and future prospects. In addition to suicide exploration in open conversation, various scales exist that can be used in a supportive manner such as Geriatric Depression Scale, Geriatric Ideation Screen, Suicide Status Form II, Nurses Global Assessment of Suicide Risk, or Suicide Risk Assessment Inventory. In addition, attention should be paid to indications that suggest an increased risk of suicide, such as suicide attempts in the history or environment of the affected person; psychiatric illness, especially depression and addiction; the presence of certain psychopathological symptoms such as suicidal thoughts, actions and impulses, feelings of hopelessness and helplessness, and psychotic symptoms; Chronic somatic comorbidities and their consequences, such as limitations in daily life, restricted autonomy, and chronic pain; and psychosocial factors, such as loss of partner, loneliness, lack of social support [1].

Diagnostics according to ICD-10

Diagnosis is based on cross-sectional findings with determination of the syndrome as well as determination of severity and assessment of progression. Overall, the syndrome diagnosis must persist for at least 14 days for the criteria for a depressive episode to be met. According to the operationalized approach, main symptoms such as depressed mood, loss of interest and joylessness, as well as decreased drive and increased fatigability, are distinguished from additional symptoms such as impaired concentration and attention, decreased self-esteem and self-confidence, feelings of guilt, feelings of worthlessness, negative future perspectives, suicidal thoughts or actions, sleep disturbances, and decreased appetite. Depending on the number of symptoms present, it is classified as mild, moderate or severe episode. In severe episodes, there may also be psychotic symptoms in the form of delusions of sin, impoverishment, or illness; more rarely, there may be nihilistic delusions. Hallucinations are not excluded, usually existing in psychotic depression as auditory or olfactory hallucinations [1].

However, the ICD-10 does not provide a standardized specification to quantify psychomotor activation in depression. Clinically, however, depression in the context of Alzheimer’s dementia is often associated with a significantly higher need for care or social support. In unipolar course, a distinction is made between depressive episode, if the depression occurs only once, and recurrent course, if it occurs several times. If, in addition, mania occurs during the course of the disease, a bipolar disorder is present. In addition, an adjustment disorder with depressive or anxious symptoms must also be considered in the differential diagnosis of depression in the elderly, especially in reactions to severe physical illness or grief reactions after partner loss. Patients with a prolonged grief response may develop the full-blown depression in approximately 15% of cases [4].

Even if the symptoms of depression in older patients do not differ from those in younger patients, the clinical picture is different. For example, major symptoms such as sadness are often less expressed. Instead, depression often manifests itself via physical complaints such as sleep disturbance, globus sensation, or functional cardiac dysfunction. In addition, cognitive impairment may occur with depressive episodes that only partially improve even during remission. Several studies suggest that recurrent depressive disorder earlier in life increases the risk for degenerative dementia in old age.

Acquisition tools specifically for older people

Since the recording of depressive symptoms in the elderly may be confounded with symptoms, somatic or cerebro-organic disease, and adverse effects of medication [5,6], recording instruments have been developed and tested specifically for the elderly. In addition, sensory impairments may interfere with acquisition, and in the case of cognitive impairments, verbal problems may create a false picture.

As a self-report questionnaire, the geriatric depression scale (GDS) is the most widely used [7]. In addition, the “Depression in Aging” scale (DIA-S) is also known in the German-speaking world [8]. It is based on the ICD-10 diagnostic criteria and has good validity. For screening in adults, the Beck Depression Inventory II (BDI II) is a suitable tool, which is also widely used internationally and can also be applied in older individuals [9]. The Montgomery-Asberg Depression Rating Scale (MADRS) is also used independently of age and has been validated in the older age group [10]. In the Hamilton Depression Scale (HAMD), on the other hand, somatic and motor syndrome components predominate, whereas motivational, affective, and cognitive symptoms are less considered. Its use in elderly patients must therefore be done judiciously [11]. Depression screenings for people with dementia also present a special challenge. The Cornell Scale for Depression in Dementia (CSDD) was developed for this case [12].

In the case of depression occurring for the first time in old age, brain-organic or somatic causes must be clarified as a differential diagnosis in addition to the psychiatric diagnosis. In addition, laboratory tests are indicated in the monitoring of psychopharmacological treatment of depression in terms of therapeutic drug monitoring. The most important differential diagnosis of depression in old age is the onset of dementia, the likelihood of which increases with age. For this reason, an appropriate dementia evaluation is recommended to exclude an organic cause of depression according to international treatment recommendations [13].

Depending on the severity, the treatment of depression consists of individual psychosocial interventions, psychotherapeutic treatment, and psychopharmacotherapy for those affected, with the involvement of their relatives. In addition, in old age, comorbid somatic diseases must also be taken into account and treated. The pharmacotherapy of choice is also the use of antidepressants in patients of older age with moderate to severe depression. However, some meta-analyses suggest that their effect size may decrease with age [14,15]. In addition to the general efficacy, other factors play a role in the selection of a suitable antidepressant, such as the exact diagnosis, the clinical-phenomenological picture, and the drug characteristics such as the side effect profile and the risk of interactions. In elderly, often multimorbid patients, the indication must be weighed particularly carefully with regard to the risk assessment of polypharmacy. This also includes an interaction check for risk assessment.

In principle, the Swiss treatment recommendations for unipolar depression also apply to depression in old age [16]. In principle, substances with central anticholinergic properties should not be used because they can reduce cognitive performance, lead to urinary and bowel dysfunction, as well as cardiac problems and, in the worst case, delirium. Blood pressure-active substances with orthostasis should also be avoided. In addition, with serotonergic antidepressants, the syndrome of inadequate ADH secretion (SIADH) with hyponatremia and its consequences should be considered. The potential prolongation of QTC time should also be considered with selective serotonin reuptake inhibitors (SSRIs).

Combined covariate effects

In this context, a Bayesian network meta-analysis examined the optimal dosage of antidepressants in major depressive disorder (MDD) as a function of age. The results suggest that the combined covariate effect of dose and age provides a better basis for assessing the clinical benefit of antidepressants than considering dose or age separately, and therefore may inform decision makers to accurately determine dosing recommendations for antidepressants in MDD [17].

Agomelatine and escitalopram were suggested to be beneficial balanced antidepressants according to the analysis, which can be explained by their pharmacological profiles. Agomelatine, a combination of norepinephrine and dopamine disinhibition (NDDI) and melatonergic agonism, has a favorable side effect profile primarily due to the fact that it does not impair sexual function, weight gain, or metabolic syndrome and positively regulates sleep quality. However, the equilibrium advantage for agomelatine observed in the analysis was due to relatively good tolerability rather than superior efficacy. The comparably low efficacy may be one reason why agomelatine is still one of the least commonly used antidepressants.

Escitalopram, one of the most commonly used antidepressants after citalopram, has a unique mechanism, according to the analysis, which is why it appears to be more effective than citalopram. Accordingly, there is a synaptic interaction for the racemate citalopram (which consists of the S- and R-citalopram enantiomers) in that the presence of R-citalopram inhibits the more active S-citalopram from binding to the serotonin (5-hydroxytryptamine [5-HT])site of the serotonin transporter (SERT). For this reason, escitalopram, which consists only of the S-citalopram enantiomer, has a pharmacologically broader therapeutic range and a more rapid mode of action. Thus, in contrast to agomelatine, the favorable balance observed here for escitalopram is equally attributable to efficacy and tolerability.

Antidepressants and physical activity

Several studies have shown that aerobic exercise (AE) can also be a non-pharmacological strategy to improve the treatment of depression while reducing the burden of somatic comorbidity of this pathology [18,19]. Physical activity stimulates neurogenesis and synaptic plasticity through the synthesis and release of brain-derived neurotrophic factor (BDNF), induces physiological changes in endorphin and monoamine levels, increases plasma concentrations of transforming growth factor-β1 (TGF-β1), and decreases cortisol levels; it may also act as an anti-inflammatory factor by increasing IL-10 levels and suppressing TNF-α production, thus exerting antidepressant-like effects.

Physical activity thus modulates many mechanisms and systems involved in the pathophysiology of depression. It can also act on the core symptoms of depression by reducing sadness, anhedonia and sleep disturbances, improving metabolic control and cognitive functions such as attention and concentration, and reducing the risk of developing depression and dementia. Finally, several clinical trials have highlighted the effect of physical activity as an adjunctive treatment for patients with moderate to severe depression and underlined the existing synergistic effect between physical activity and conventional pharmacological treatment. This synergistic effect may be particularly important in elderly patients who are at increased risk of dementia [20].

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