Treatment

In general, the pharmacological treatment of nonpsychotic major depressive disorder in elderly persons is only partially successful: only about half of older adults with depression improve with initial antidepressant monotherapy.55 Many factors may predict a more difficult-to-treat depression, including coexisting anxiety, low self-esteem, poor sleep, and a high coexisting medical burden.56 Being aware of these and other predictors of a difficult-to-treat depression gives the clinician more reasonable expectations about a patient’s likely treatment outcome. Getting well and staying well is the goal of patients; thus, clinicians should treat to remission of depression, not merely to response.56

Maintenance treatment with the same regimen that has been successful in relieving the depression strongly improves the patient’s chances of remaining depression-free. In a recent trial of maintenance treatments, patients 70 years or older with major depression who had responded to initial treatment with paroxetine and psychotherapy were less likely to have recurrent depression if they received 2 years of maintenance therapy with paroxetine.57 Monthly maintenance psychotherapy did not prevent recurrent depression. This is unexpected given earlier reports of improved response to the combined treatments, and thus, needs to be replicated.

Randomized trials have compared different strategies for management of nonmajor depression, mostly in primary care settings. In a recent meta-analysis, Pinquart and colleagues58 integrated the results of 89 controlled studies of treatments for acute major depression (37 studies) and other depressive disorders (52 studies conducted with mixed diagnostic groups, including patients with major depression, minor depression, and dysthymia). Psychosocial treatments had larger effect sizes for less severe forms of depression than pharmacological treatments.

Two collaborative trials have addressed the efficacy of antidepressant treatment in patients with depressive syndromes treated in primary care settings. The Prevention of Suicide in the Primary Care Elderly Collaborative Trial (PROSPECT) study, which was supported by the NIMH, and theImproving Mood: Promoting Access to Collaborative Treatment for Late Life Depression (IMPACT) study, which was supported by the Hartford Foundation, evaluated the effectiveness of current models by nurse health specialists.59,60 Results showed that the PROSPECT intervention substantially reduced suicidal ideation at rates comparable to those seen in earlier efficacy studies and in specialty mental health clinical settings.61 The IMPACT intervention was effective in improving symptomatic and functional outcomes for older primary care patients with major depression or dysthymic disorder.60 The studies on collaborative treatments are important and the components of collaborative care can be transported into clinical practice emphasizing early diagnosis and treatment of depression in primary care settings.

Case Vignette

Esther, a 72-year-old, presents with complaints of insomnia, weight loss, and sadness over the loss of her husband 2 years ago. She is socially isolated, lives alone, and rarely leaves her house. Esther is able to cook simple meals. She still drives short distances, but on several occasions she has forgotten her appointments.

Her medical problems include hypertension, coronary artery disease, hyperlipidemia, and stress incontinence. When her primary care physician prescribed 10 mg of nortriptyline at night to treat the depression, incontinence, insomnia, and poor appetite, she became agitated, confused, and disoriented. She was taken to the emergency department where delirium was diagnosed. The patient was admitted to the geriatric psychiatry unit.

A CT scan of her head showed some age-related generalized atrophy and old microvascular disease in the deep white matter and periventricular but no acute stroke. The ECG showed QTC-interval prolongation but no acute ischemic changes.

Esther was given 0.5 mg of haloperidol for agitation and belligerence, and nortriptyline was discontinued. Over the next 5 days, her confusion and agitation subsided, but she showed mild extrapyramidal signs caused by the haloperidol, which was discontinued by day 5.

Neuropsychological testing revealed deficits in executive functioning and psychomotor slowing; however, dementia was ruled out. Esther was given 15 mg of mirtazapine at night: she became more animated, less withdrawn, participated in group activities, and enjoyed the company of other patients. Her appetite and sleep improved as well. There were no changes from baseline on subsequent ECGs, and Esther was discharged with recommendations for admission to a day treatment program and individual psychotherapy or grief counseling with structured activities to increase social stimulation, as well as recommendations for local resources and support groups.

The antidepressant selection that was ultimately successful for Esther considered her vulnerability to anticholinergics and the central and cardiac adverse effects of nortriptyline that led to the patient’s confusion and hospitalization. The selection of mirtazapine addressed her symptoms of depression, as well as incontinence, insomnia, and poor appetite without exposing Esther to the detrimental anticholinergic adverse effects.

Conclusions

Despite recent advances in our understanding of pathophysiology of geriatric depression and the development of treatment approaches similar to that in younger adults, the available treatments are only modestly effective. Our current understanding of the pathophysiology of geriatric depression complicated by medical, vascular, and neurodegenerative processes should lead to the development of more personalized treatment approaches based on individual risk factors. For example, treatment of depression should be different for those who are depressed due to complicated bereavement than for those who become depressed at the beginning of Alzheimer disease. So far, recommended treatments have not differed and have followed the drug development paradigm for younger adults: no consideration has been given to differences in pathophysiology in aging adults, which poses challenges to future research.

General considerations when choosing a drug regimen for older adults should include age-related changes in pharmacokinetics and pharmacodynamics of the drugs and in the structure and function of the brain and other organs that lead older adults to be more sensitive to both therapeutic and toxic effects of psychotropic medications. Such changes necessitate lower doses and slower dose titration. Although the effective dose may be similar to that for younger adults, the initial dose of psychotropic medications for older adults should be one-third to one-half of that for younger adults and titrated slowly. The groups that may be particularly vulnerable to the adverse effects and drug-drug interactions include frail older adults with multiple medical problems or those with cognitive impairment, dementia, or other neurodegenerative disorders or who have had a stroke. Lower doses of drugs and augmentation strategies with other drugs and supplements should be considered (eg, cognitive enhancers and neuroprotective agents in patients with cognitive impairment; or psychostimulants or dopaminergic agents in patients with apathy or Parkinson disease). Table 2 (Table restricted. Please see print version for content.)  lists the recommended dosages of antidepressants for older adults.
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