Geriatric Mood Disorders

The aging of the US population and the high prevalence of depression among the elderly attest to its public health significance.¹ The prevalence of depression is 8% to 16% in community-dwelling older persons, and the prevalence of mixed anxiety-depression is 1.8%.² Depression complicates medical illnesses and their management, and it increases health care use, disability, and mortality.³ This article focuses on the recent research data on diagnosis, etiopathogenesis, treatment, and prevention in unipolar, bipolar, psychotic, and subsyndromal depression.

Differential diagnosis and treatment of depressive spectrum disorders

Depressive symptoms in the elderly are not adequately captured by the criteria of major depression as outlined in DSM-III through DSM-IV-TR.⁴ There is evidence from epidemiological, longitudinal, neuroimaging, cognitive, and genetic studies that supports the idea of a continuum of depressive disorders, ranging from the very mild subthreshold to major unipolar and bipolar depression.⁵ Minor depression affects up to 50% of residents in long-term—care facilities and up to 25% in the primary care setting, and it is associated with considerable discomfort, disability, and risk of morbidity, as well as excessive use of non—mental health services.^6,7 The term “subsyndromal depressive spectrum disorder” describes a group of states operationally defined by the presence of 2 or more concurrent symptoms of depression for most or all of the time, for at least 2 weeks, associated with evidence of social dysfunction, in patients who do not meet criteria for a diagnosis of minor depression, major depression, and or dysthymic disorder. (Table 1)^8,9

Bipolar affective disorder is fairly common in elderly persons, with a prevalence of 0.1% to 0.43% in the United States. However, between 10% and 20% of geriatric patients with mood disorders have bipolar disorder, as do 5% of those admitted to geropsychiatric inpatient units.10 While late-onset bipolar disorder is relatively rare, recurrence of remitted disease frequently occurs in late life.¹¹ Subramaniam and colleagues¹² identified higher cerebrovascular risk in elderly patients with late-onset bipolar disorder compared with patients who had the early-onset disorder. These patients often present a tremendous treatment challenge because of substantial medical comorbidity and age-related variations in response to therapy. Unfortunately, the management of geriatric bipolar disorder has been relatively neglected compared with the condition in the younger population.^10,11,13

Lithium, divalproex sodium(Drug information on divalproex sodium), carbamazepine(Drug information on carbamazepine), lamotrigine(Drug information on lamotrigine), atypical antipsychotics, and antidepressants have been found to be beneficial in the treatment of elderly patients with bipolar disorder. In an open trial, flexible dose aripiprazole(Drug information on aripiprazole) with a mean daily dose of 10.2 mg was effective as an adjunct medication.¹⁴ The NIMH-funded Geriatric Bipolar (Geri-BD) trial is ongoing and will provide additional information about the use of lithium(Drug information on lithium) and valproic acid with and without risperidone(Drug information on risperidone) in older adults with bipolar mania. Major depression with psychotic features occurs in 15% of community sample populations and in 25% of inpatient mixed-age sample populations. Among geriatric inpatients, the rate may reach 45%.¹⁵ Unfortunately, the appropriate diagnosis of psychotic depression is missed in about 30% of emergency department admissions.¹⁶ Despite recommended antidepressant/antipsychotic combination treatment, the use of antipsychotics in combination therapy for psychotic depression remains low (5%).¹⁷

Alexopoulos and colleagues¹⁸ and Krishnan and colleagues¹⁹ proposed the concept of vascular depression on the premise that cerebrovascular disease, documented on structural neuroimaging (CT and MRI) studies, may be causally related to geriatric depressive syndromes. Subcortical ishemic depression affects clinical presentation, long-term outcomes, and response to antidepressant therapy.²⁰ The Figure delineates the pathways to geriatric depression.

In a study of patients with DSM-III-R criteria for depression, silent cerebral infarctions were reported in 65% of 20 patients.²¹ Recent observations suggest that in elderly persons, smaller brain volumes and white matter hyperintensities may provide complementary, albeit autonomous pathways to late-life major depressive disorder.^22,23 Taylor and colleagues²⁴ observed that greater anterior white matter lesion volumes were associated with higher diffusivity and lower anisotropy in the white matter of the dorsolateral prefrontal cortex and with higher diffusivity of the internal capsule and white matter lateral to the anterior cingulate cortex. The neuropathological correlates of small strokes or signal hyperintensities on MRI or CT are diverse and represent ischemic vascular change.²⁵

Although there are no specific treatments for vascular depression, general vascular prevention approaches using lipid-lowering drugs, fish oil, or aspirin(Drug information on aspirin) are applicable. The recent study by Jorge and colleagues²⁶ examined the efficacy of repetitive transcranial magnetic stimulation (rTMS) for treatment of vascular depression in 92 patients who were randomly assigned to receive active or sham rTMS of the left dorsolateral prefrontal cortex. Response rates to rTMS were negatively correlated with age and lower frontal gray matter volumes. This approach applies to subcortical ischemic depression, a diagnosis corresponding to the “vascular depression” hypothesis.