Correspondence : Min-Soo Lee, MD, PhD, Department of Psychiatry, Korea University College of Medicine, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-705, Korea
Tel : +82-2-920-5354, Fax : +82-2-923-3507, E-mail : leeminso@korea.ac.kr

Introduction

Depression is frequent in older adults and is the second most disabling psychiatry syndrome (following memory loss) in this population group. Geriatric depression is distinct from depression in other age ranges in that it causes frequent somatic symptoms, psychomotor retardation, high suicidal rates or cognitive decline. Elderly depression aggravates the global health state, deteriorates quality of life and causes substantial social waste, by obliging others to be responsible for nursing those afflicted with this disorder.
Psychopharmacologic development has provided elderly patients with a number of safe antidepressants. This often enables the successful treatment of the depression accompanied with physical diseases, which frequently occurs among elderly patients. Despite this improvement, geriatric depression is still not properly recognized or diagnosed and lacks appropriate treatment. In this paper, we offer a review of the epidemiology, pathophysiology, diagnosis, and treatment of geriatric depression.

Epidemiology

The prevalence of geriatric depression varies with the study, examining tool, or diagnosis criteria. An epidemiology survey conducted in the United States found that 1-4% of the general elderly population have major depression.¹ Specifically, the analysis of the results by gender in this study showed that it occurs twice as often in females as in males. The prevalence of minor depression was 4-13%.¹ Dysthymic disorder, which is characterized by milder symptoms that last more than 2 years, occurs in about 2% of the elderly.¹ An elderly person has an almost equal or slightly less chance than a middle-aged person to have clinically significant symptoms of depression (prevalence 8-16%).¹
Several surveys have been conducted in Korea as well, regarding the prevalence of geriatric depression. The results of these studies vary with the regions, due to their different characteristics. The epidemiology surveys conducted within the Gyeonggi-do region indicated that the prevalence of major depression in persons 65 years of age or older ranges from 7.8% to 10%.^2,3
The prevalence of geriatric depression is higher in medical settings than in the general community. 10-12% of hospitalized patients and 12-14% of individuals who live in nursing homes have major depression.¹ Taken together, these results indicate that the epidemiology of depression varies across regions and nations and that it is more prevalent among elderly people with either physical diseases or living in nursing homes.

Pathophysiology

A number of studies have been conducted on the cause of geriatric depression recently, but it has not yet been ascertained. However, some biological and psychosocial factors attributable to geriatric depression have been identified.
Hereditary factors could predispose to late-life depressive syndromes. In community-residing elderly twins, heredity accounted for 18% of the variation in depressive symptoms.⁴ The genetic markers for late-life depression have not been identified. However, the results of association study in Swedish twin sample suggest that there is an association between the 5-HTR2A gene variant and depressed mood in the elderly men.⁵
The disruption of the regulation of the hypothalamicpituitary-adrenal axis, sleep cycle, and other circadian rhythms is more likely to be present among older persons than among younger persons.⁶ These problems have also been associated with major depression. Depressed elderly patients had longer P300 latency than normal elderly subjects.⁷ Elderly depressed patients (over 60 years of age) exhibited significant reductions in the number of platelet-tritiated imipramine binding sites.⁸
In recent years, considerable attention has been paid to the association of depression with lesions in the subcortical structures and their frontal projections in the brain.⁹ Frontostriatal dysfunction could predispose to late-life depression. Executive dysfunction, a clinical expression of frontostriatal abnormalities, is common in late-life depression,¹⁰ and persists after the improvement of mood-related symptoms.¹¹ Low volumes of frontostriatal structures have been documented in late-life depression.¹²
Various life events could cause geriatric depression. Older persons must adapt to many adverse life experiences, especially the losses of relatives and friends. A Korean study indicated that depressive symptoms are associated with the loss of spouse, a current physical illness, or low socioeconomic status.¹³ Bereavement is particularly connected with depression. During the first year of bereavement, 10-20% of surviving spouses developed depression.¹⁴ The prevalence of major depression continues to increase during the second year of bereavement.¹⁵ At the end of the second year of bereavement, 14% of bereaved spouses have major depression, compared with 1-4% of the general elderly population.¹

Diagnosis and Differential Diagnosis

A psychiatric interview is essential to the diagnosis of geriatric depression and needs to include interviews of all family members as well as the patient. These interviews are conducted for the purpose of acquiring information such as the duration of the current depressive episode, past history of depression, abuse of substances or alcohol, response to previous treatment, family history of depression, suicidal ideation or attempt and loss of physical function. Although older persons may show some tendency to mask their depressive symptoms, a careful interview almost always discloses clinically significant depression if it is present.
A thorough mental status examination is important. The clinician should pay attention to disturbances of motor behavior and perception, hallucination, disturbances of thinking and cognitive function. Neuropsychological tests might be used to differentiate depression from dementia. A number of clinical assessment scales such as the Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale, Global Assessment Scale, and Korean Depression Scale¹⁶ can help in diagnosing depression. The scores on these scales can be useful in the process of treatment, since they provide some idea of the severity or improvement of depression.
Geriatric depression is often caused by medical and neurological disorders.¹⁷ If medical disease or medication leads to the development of depression, a diagnosis of depression due to a general medical condition or medication-induced depression can be made. Depression is often present in individuals with dementia and cerebrovascular disease. The cross-sectional prevalence of major depressive disorder was found to be 17% in patients with Alzheimer's dementia.¹⁸ Sobin and Sacheim reported a higher prevalence of depression in subjects with subcortical dementia than in those with Alzheimer's disease.¹⁹ This suggests that, when conducting physical examinations of elderly patients, a neurologic examination needs to be included to identify the presence of soft neurologic signs. Moreover, some tests, such as the blood count, thyroid panel and measurement of B12 and folate levels, are useful in screening for medical illness that is present with concurrent depressive symptoms. An adjustment disorder with depressed mood secondary to physical disability or chronic illness is among the frequent causes of elderly depression.²⁰
Bereavement could be a significant factor in geriatric depression. Although not a diagnostic criterion for major depression, bereavement often leads elderly people to suffer from depressive symptoms that deteriorate their quality of life and these symptoms occasionally develop into severe depression.

Treatment

The clinical management of geriatric depression involves pharmacotherapy, electric convulsive therapy (ECT), psychotherapy, and collaboration with the family members. The treatment plan should start with an assessment of whether there are any medications or illnesses that predispose the patient to depressive symptoms. If there are any, the treatment of underlying medical disease, along with suspense or reduction of unnecessary medication needs to be preceded.
While it is hard to tell which medications are more effective in treating geriatric depression, the difference of their side effects is obvious, and this provides some idea of the choice of proper medication. The pharmacological treatment of choice at present is one of the new-generation antidepressant medications. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are the antidepressants of choice, followed by bupropion and mirtazapine.^21,22 The use of antidepressant medications, particularly the SSRIs, has increased dramatically in recent years, with over 10% of people 75 years and older taking antidepressants at any given time.²³ SSRIs such as fluoxetine, sertraline, paroxetine, and citalopram can be used at a somewhat lower dose than is prescribed in the earlier stages of the life cycle. The most common adverse effects that limit the use of SSRIs are agitation and persistent weight loss.²⁰ Although the initial doses of SSRIs and SNRIs should be low, the final doses are similar to those used in young adults.²⁴ Recent research indicates that venlafaxine has a pharmacological profile that makes it an attractive choice for geriatric patients. Emerging data suggest that venlafaxine may be effective for conditions such as stroke, anxiety, and neuropathic pain that frequently accompany depressive disorders in the elderly.²⁵ Nortriptyline and desipramine might be reasonable alternatives to SSRIs in severe late-life depression.²² Each has relatively less anticholinergic effects than other tricyclic antidepressants. Amitriptyline, imipramine, doxepin, amoxapine, maprotiline, trazodone, tranylcypromine, and isocarboxazid are not preferred.²⁶
Geriatric depression is a relapsing disease. Reynolds et al. reported that 90% of elderly individuals with major depression in remission relapsed within 3 years when maintained on a placebo.²⁷ On the other hand, those maintained on nortriptyline and interpersonal psychotherapy had a recurrence rate of 20%. This suggests that antidepressant treatment needs to be maintained even after the improvement of symptoms. The dosage of antidepressants for maintenance should be the same as that for acute treatment. In patients who have had a single severe episode of depression, antidepressant drug treatment should be continued for at least 1 year.²⁴
Older people who do not respond to antidepressant medications or who experience significant side effects resulting from the medications may be candidates for ECT. The other candidates for ECT are those persons who experience a severe depressive episode or psychotic symptoms.²⁰ ECT is a safe and effective treatment for older adults with proper medical support.
Several studies demonstrated that cognitive-behavioral therapy, supportive psychotherapy, problem-solving therapy, and interpersonal therapy are preferred for elderly depression.²⁶ For geriatric depression caused by stressful events, psychotherapy alone or psychotherapy in conjunction with an antidepressant is recommended.²⁸ Cognitive therapy is as effective in elderly individuals as it is in younger adults.²⁹ Psychoeducation can help patients and their families with treatment adherence.³⁰ Any effective therapy for depression in older persons must include collaboration with the family. Families are often the most important allies of clinicians treating depressed older patients.

Conclusion

Geriatric depression is a frequent and disabling psychiatric syndrome. With the increasing number of older persons, closer evaluation is required for the diagnosis of depression. The epidemiology, cause, and clinical features of elderly depression are distinct from depression in other age groups. The treatment of depression in the elderly is complex in that it involves the consideration of the role of comorbid diseases, cognitive changes, concomitant medications, and the status of the patient's support systems. The most favorable results can be achieved with a multimodal and optimal approach.

1. Blazer DG. Depression in late life: review and commentary. J Gerontol A Bio Sci Med Sci 2003;58:249-265.

2. Lee MS, Choi YK, Jung IK, Kwak DI. Epidemiological study of geriatric depression in a Korea urban area (in Korean). J Korean Geriatr Psychiatry 2000;4:154-163.

3. Oh BH, Kim HS, Kim JH, Cho HS, Cho KH, Yoo KJ. Epidemiologic study of cognitive impairment and depressive symptoms of the elderly in a Korean rural community (in Korean). J Korean Geriatr Psychiatry 1998;2:176-186.

4. Gatz M, Pedersen N, Plomin R, Nesselrade J, McClearn G. Importance of shared genes and shared environments for symptoms of depression in older adults. J Abnorm Psychol 1992;101:701-708.

5. Jansson M, Gatz M, Berg S, Johansson B, Malmberg B, McClearn GE, et al. Association between depressed mood in the elderly and a 2-HTR2A gene variant. Am J Med Genet 2003; 120:79-84.

6. Blake LM. Aging, stress, and affective disorders. Semin Clin Neuropsychiatry 2001;6:27-31.

7. Kalayam B, Alexopoulos GS, Kindermann S, Kakuma T, Brown GG, Young RC. P300 latency in geriatric depression. Am J Psychiatry 1998;155:425-427.

8. Nemeroff CB, Knight DL, Krishnan RR, Slotkin TA, Bissette G, Melville ML, et al. Marked reduction in the number of platelet-tritiated imipramine binding sites in geriatric depression. Arch Gen Psychiatry 1988;45:919-923.

9. Krishnan KR. Neuroanatomic substrates of depression in the elderly. J Geriatr Psychiatry Neurol 1993;6:39-58.

10. Lockwood KA, Alexopoulos GS, van Gorp WG. Executive dysfunction in geriatric depression. Am J Psychiatry 2002;159:1119-1126.

11. Nebes RD, Pollock BG, Houck PR, Butters MA, Mulsant BH, Zmuda MD, et al. Persistence of cognitive impairment in geriatric patients following antidepressant treatment: a randomized, double-blind clinical trial with nortriptyline and paroxetine. J Psychiatr Res 2003; 37:99-108.

12. Ballmaier M, Toga AW, Blanton RE, Sowell ER, Lavretsky H, Peterson J, et al. Anterior cingulate, gyrus rectus, and orbitofrontal abnormalities in elderly depressed patients: an MRI-based parcellation of the prefrontal cortex. Am J Psychiatry 2004;161:99-108.

13. Lee MS, Nam JW, Cha JH, Kwak DI. Factors affecting the severity of depressive symptoms in the elderly (in Korean). J Korean Neuropsychiatr Assoc 1999;38:1063-1070.

14. Alexopoulos GS. Late-life mood disorder (3rd ed). In: Sadavoy J, Jarvik LK, Grossberg GT, Mayers BS, editors. Comprehensive textbook of geriatric psychiatry. New York: WW Norton and Company, 2004.

15. Zisook S, Schuchter SR, Sledge R. Diagnostic and treatment considerations in depression associated with late-life bereavement. In: Schneider LS, Reynolds CF, Lebowitz BD, Friedhoff AJ, editors. Diagnosis and treatment of depression: results of the NIH consensus development conference. Washington: American Psychiatric Press, 1994.

16. Lee MS, Rhee MK. A development of Korea Depression Scale (in Korean). J Korean Neuropsychiatr Assoc 2003;42:492-506.

17. Alexopoulos GS, Buckwalter K, Olin J, Martinez R, Wainscott C, Krishnan KR. Comorbidity of late-life depression: an opportunity for research in mechanisms and treatment. Biol Psychiatry 2002;52:543-558.

18. Wragg RE, Jeste DV. Overview of depression and psychosis in Alzheimer's disease. Am J Psychiatry 1989;146:577-589.

19. Sobin C, Sacheim HA. Psychomotor symptoms of depression. Am J Psychiatry 1997;154:4-17.

20. Hales RE, Yudofsky SC. Textbook of clinical psychiatry (4th ed). Washington: American Psychiatric Publishing, 2002.

21. Salzman C, Small GH. Treatment of with new antidepressants (4th ed). In: Salzman C, editor. Clinical geriatric psychopharmacology. Philadelphia: Lippincott, Williams and Wilkins, 2005.

22. Alexopoulos GS, Lerner DM, Salzman C. Treatment of depression with tricyclic antidepressants, monoamine oxidase inhibitors, and psychostimulants (4th ed). In: Salzman C, editor. Clinical geriatric psychopharmacology. Philadelphia: Lippincott, Williams and Wilkins, 2005.

23. Blazer DG. Psychiatry and the oldest old. Am J Psychiatry 2000;157:1915-1924.

24. Alexopoulos GS. Depression in the elderly. Lancet 2005;365:1961-1970.

25. Staab JP, Evans DL. Efficacy of venlafaxine in geriatric depression. Depress Anxiety 2000;12(suppl 1):63-68.

26. Alexopoulos GS, Katz IR, Reynolds CF 3rd, Carpenter D, Docherty JP. The expert consensus guideline series: pharmacotherapy of depressive disorders in older patients. Postgrad Med Special Report 2001;Spec No Phamacotherapy:1-86.

27. Reynolds CF, Frank E, Perel JM, Imber SD, Cornes C, Miller MD, et al. Nortriptyline and interpersonal psychotherapy as maintenance therapies for recurrent major depression: a randomized controlled trial in patients older than 59 years. JAMA 1999;281:39-45.

28. Bartels SJ, Dums AR, Oxman TE, Schneider LS, Arean PA, Alexopoulos GS, et al. Evidence-based practices in geriatric mental health care: an overview of systematic reviews and meta-analyses. Psychiatr Clin North Am 2003;26:971-990.

29. Koder DA, Brodaty H, Anstey KJ. Cognitive therapy for depression in the elderly. Int J Geriatr Psychiatry 1996;11:97-107.

30. Gilbody S, Whitty P, Grimshaw J, Thomas R. Educational and organizational interventions to improve the management of depression in primary care: a systematic review. JAMA 2003;289:3145-3151.