Conventional and new antidepressant drugs in the elderly

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Abstract

Depression in the elderly is nowadays a predominant health care problem, mainly due to the progressive aging of the population. It results from psychosocial stress, polypathology, as well as some biochemical changes which occur in the aged brain and can lead to cognitive impairments, increased symptoms from medical illness, higher utilization of health care services and increased rates of suicide and nonsuicide mortality. Therefore, it is very important to make an early diagnosis and a suitable pharmacological treatment, not only for resolving the acute episode, but also for preventing relapse and enhancing the quality of life. Age-related changes in pharmacokinetics and in pharmacodynamics have to be kept into account before prescribing an antidepressant therapy in an old patient. In this paper some of the most important and tolerated drugs in the elderly are reviewed. Tricyclic antidepressants have to be used carefully for their important side effects. Nortriptyline, amytriptiline, clomipramine and desipramine as well, seem to be the best tolerated tricyclics in old people. Second generation antidepressants are preferred for the elderly and those patients with heart disease as they have milder side effects and are less toxic in overdose and include the so called atypicals, such as selective serotonin reuptake inhibitors, serotonin noradrenalene reuptake inhibitors and noradrenaline reuptake inhibitors. Monoamine oxidase (MAO) inhibitors are useful drugs in resistant forms of depression in which the above mentioned drugs have no efficacy; the last generation drugs (reversible MAO inhibitors), such as meclobemide, seem to be very successful. Mood stabilizing drugs are widely used for preventing recurrences of depression and for preventing and treating bipolar illness. They include lithium, which is sometimes used especially to prevent recurrence of depression, even if its use is limited in old patients for its side effects, the anticonvulsants carbamazepine and valproic acid. Putative last generation mood stabilizing drugs include the dihydropyridine L-type calcium channel blockers and the anticonvulsants phenytoin, lamotrigine, gabapentin and topiramate, which have unique mechanisms of action and also merit further systematic study. Psychotherapy is often used as an adjunct to pharmacotherapy, while electroconvulsant therapy is used only in the elderly patients with severe depression, high risk of suicide or drug resistant forms.

Introduction

Depression in the elderly is nowadays a predominant health care problem, mainly due to the progressive aging of the population. In fact, the statistics of the United Nations and the World Bank pointed out that by the year 2010 approximately 7.3% of the world’s population will be over the age of 65 and by the year 2030 a further increase up to 20% is foreseen (Mendlewicz, 1998). Depression is the most common psychiatric disease in the elderly; major depression may affect from 10 to 20% of hospitalized elderly, while from 10 to 34.5% of older persons in the community may have depressive symptoms if mild forms are considered too (Blazer, 1989, Murphy et al., 1988, Small, 1991, Weissman et al., 1988, Linden et al., 1998). In the Consensus Statement on the Diagnosis and Treatment of Depression in Late Life (National Institute of Health), it was emphasized that depression in the elderly is a persistent or recurrent disorder resulting from psychosocial stress or physiologic effects of disease and can lead to disability, cognitive impairments, increased symptoms from medical illness, increased utilization of health care services and increased rates of suicide and nonsuicide mortality (Katz et al., 1994).

Data from Diagnostic and Statistical Manual for Mental Disorders, 4th edition (DSM-IV) have shown that major depressive disorder is more frequent in young people, whilst dysthymia and depressive disorder not otherwise specified prevail among the elderly (Gottfries, 1998). These results don’t mean that depression is less severe in elderly people than in younger, since high suicide rates have been especially found in the former.

Moreover, depression is difficult to diagnose in elderly people; depressive symptoms are often masked by somatic complaints or by cognitive symptoms, conditions once called ‘masqued depression’ or ‘pseudodemence’. Therefore, depression in the elderly is often under-recognized and under-treated (Lecrubier, 1998); this may be due to the mistake, both from the physician and from the patient, of considering depression as a physiologic response to aging. Other factors may be the lack of consciousness of disease from the patient, the presence of concomitant diseases, especially dementia (Bayer and Pathy, 1989) and the usully atypical onset of depression in elderly people (Blazer, 1980). The increased incidence and prevalence of depression with aging can be also explained considering some stressors which elderly people frequently have to face, such as physical disability, bereavement, loss of prestiges, cognitive abilities and social isolation (Koenig and Blazer, 1992). In fact, it was shown that the nature and quality of social support, defined by the number of relationships with friends and relatives is one of the major risk factors for depression in the elderly (Krause et al., 1989, Russel and Cutrona, 1991, Owmank et al., 1992). Female sex, widowhood and single life are risk factors for depression too (Dufouil et al., 1995, Blazer et al., 1991, Okwumabua et al., 1997). Interestingly, some studies have shown that aging itself is not a risk factor for depression (Blazer et al., 1991, Roberts et al., 1997).

Moreover, major depression may arise from disfunction of the limbic-hypothalamic-pituitary-adrenal axis (Friedlander et al., 1993). Depression may also be caused by a various number of drugs currently administered (see below); this is remarkable especially in elderly people, where polypathology is often associated to polypharmacotherapy. Depression has also global consequences on quality of life and social functioning, leading to distress, loss of role and gratification, narrowing of the social repertoire and shortening of life span (Warner, 1998). In fact, mortality may also be higher in the elderly depressed compared with controls (Murphy, 1983); the excess mortality was accounted for by a variety of diseases, such as vascular and respiratory diseases and cancer.

Section snippets

Incidence and prevalence of depression in the elderly

Epidemiologic studies of depression in the elderly raise a number of methodological problems, because of various reasons, such as the lack of a clear definition of elderly, the different populations studied (i.e. general population, patients in primary care units, instituzionalized patients, etc.), the methods of assessment used (self-rating scales, short or structured interviews, diagnostic criteria check lists) (Lepine and Bouchez, 1998). Among the methods of assessment the Zung Self Rating

Symptomatology and aetiology of depression in the elderly

Depressive disorder in younger people is often described as a tetrahedron of symptoms, where depressed mood, anxiety, reduced activity and somatic symptoms are the four corners. In elderly people, we need to distinguish depressive illness from psychological disturbances secondary to other diseases (Table 2). Depression and such secondary disturbances often occur in the same patient in the elderly.

In contrast to younger depressed patients, elderly patients often avoid reporting or showing that

Age-related changes in pharmacokinetics

Age-related changes in pharmacokinetics and pharmacodynamics may cause an increase in adverse drug reactions (ADRs) in the elderly persons. In fact, aging causes a number of changes in drug absorption, distribution, biotransformation and elimination (Galeotta et al., 1990; Voltz and Moeller, 1994). Drug pharmacokinetics may change with age as a consequence of living habits in elderly subjects, such as diet, alcohol consumption, smoking, concomitant use of other drugs and genetic polymorphism of

Mechanism of action of antidepressants

The underlying biochemical events in endogenous depression are still unknown. A disregulation of the Central Nervous System (CNS) involving the neurotransmitters NA, 5-HT and DA has been suggested and the mainstream of research in depression has principally focused on NA and 5-HT systems as having many drug development programmes. Currently, the most efficacious treatment of major and related depression, obsessive compulsive disorders and panic attacks is considered to be an increase in 5-HT

Antidepressant drugs in the elderly

The conventional drugs used in depression are:

  • 1.

    tricyclic antidepressants (TCAs);

  • 2.

    selective serotonin reuptake inhibitors (SSRI) and other new atypical antidepressants;

  • 3.

    MAO inhibitors (IMAOs);

  • 4.

    Mood stabilizing drugs, such as lithium, carbamazepine, phenytoin, valproate, verapamil, lamotrigine and gabapentin.

In case of failure of these drugs and where a high risk of suicide exists, electroconvulsive therapy can be considered.

In this review we are going to see those drugs having clinical

Electroconvulsive therapy

Electroconvulsive therapy may be used in those patients in whom pharmacological therapy was not effective and/or have an high risk of suicide. The most common side effect is a transient loss of memory, which might be avoided through the stimulation of nondominant hemisphere. Moreover the increased intracranial pressure might induce the herniation of brain tissue through tentorium. All the subjects with osteoporosis may undergo fractures for convulsive movements. Further research involving

Conclusions

Depression is a common but treatable condition in the elderly, which is often hard to diagnose, as it may be masked by hypochondriasis or somatization. Special problems in diagnosis also derives from bipolar disorder, pseudodementia, pathological grief and organic mood disorder as those related to medications or physical illness (Casey, 1994). The difficulties in diagnosing depression may lead to unnecessary investigations, delay in treatment and an increased risk of suicide, especially in men.

Acknowledgements

This research was supported by Ministero dell’Universita e della Ricerca Scientifica e Tecnologica (MURST).

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