Pharmacotherapy and Other Treatments for Elderly Patients With Depression

Gary W. Small, MD

Memory and Aging Center, Semel Institute for Neuroscience and Human Behavior, and the Geriatric Division of the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles

Major depressive disorder is a well-known and well-defined diagnosis with numerous treatment options. However, among geriatric patients, depression is an underrecognized and undertreated illness.1 Clinicians may miss depressive symptoms in older patients for many reasons, including comorbid medical illness and medication side effects, which can mask somatic depressive symptoms; the different types of depressive symptoms seen in older adults compared with younger populations; and the presence of cognitive impairment in the patient. Patients and clinicians alike may also believe that depression is a natural part of aging.

Once diagnosed, certain age-related factors can make it challenging to treat older patients. One factor can be patients’ belief that they are too old to be helped, either because there is not enough time or because they see themselves as unchangeable at this age. Physical limitations, such as hearing and vision loss, ambulatory and mobility problems, and physical discomfort, as well as transportation problems can make receiving treatment more difficult. Cognitive limitations, such as retention and recall difficulties, and even reimbursement issues can affect therapeutic engagement among the elderly. However, many evidence-based treatment modalities are available for patients with late-life depression, including psychotherapy, ECT, and medication therapy.


Older age does not preclude the possibility that a patient will respond well to a psychotherapeutic intervention. A review2 of the literature on the efficacy of psychotherapy for major depression in older patients concluded that cognitive-behavioral therapy and problem-solving therapy showed superior acute efficacy to usual care or wait-list control and that benefits lasted over a 1-year period. The review also suggested efficacy for brief dynamic therapy, interpersonal therapy, and psychotherapy combined with antidepressant treatment, but more controlled studies are needed. A meta-analysis3 that pooled results from adult and geriatric studies found similar results (AV 1AV 1).

Drug Therapies

Meta-analyses4,5 indicate generally similar efficacy among the available antidepressants that have an FDA indication for depression. However, side effect profile is critical when choosing a specific antidepressant for the older adult. To determine medication tolerability in the elderly patient, the general rule is to “start low and go slow,” but do not undertreat, and actively monitor side effects.6 Age-related pharmacokinetics and pharmacodynamics should also be kept in mind when choosing an antidepressant. With age comes a reduction in gastrointestinal, renal, and liver function; also, albumin levels are often lower, the fat-to-muscle ratio is increased, and receptor-site sensitivity for many drugs is increased. Polypharmacy, which is common in older patients, can lead to drug-drug and drug-disease interactions.

TCAs. The TCAs have the advantage of proven efficacy and low cost. However, discontinuation rates are higher for TCAs than for SSRIs because of their associated side effect profiles (AV 2AV 2).4,6 Side effects of TCAs include dry mouth, constipation, drowsiness, dizziness, and lethargy. The TCAs can also affect the cardiovascular system, are associated with orthostatic hypotension (which could lead to falls in older patients), and have the potential for lethality in overdose.

SSRIs. All SSRIs are effective in treating late-life depression.6 Advantages of SSRIs over TCAs include minimal toxicity, avoidance of autonomic side effects such as hypotension, less sedation, and ease of administration. Side effects of SSRIs include nausea, vomiting, sleep disturbances, gastrointestinal symptoms, sexual side effects, hyponatremia, drug interactions, and possibly increased cost.4,6

MAOIs. The advantages of MAOI treatment include few cardiac effects and effectiveness for atypical depression.7 However, disadvantages include orthostatic hypotension, potential hypertensive crisis due to certain food and drug interactions, and other dangerous drug interactions.6

Other antidepressant agents. Mirtazapine, bupropion, nefazodone, venlafaxine, and trazodone are effective in treating depression in the elderly.6 Mirtazapine may cause sedation and increased appetite, while bupropion does not cause sedation but can increase the risk for seizures at higher doses. Venlafaxine may be associated with hypertension. Trazodone is rarely used as a primary therapeutic agent because of limited potency and significant side effects but can be used as a hypnotic in conjunction with an SSRI. Nefazodone is rarely used as a primary therapeutic agent because of concerns about hepatotoxicity.


Electroconvulsive Therapy

A highly effective form of treatment for severe depression,8 ECT is also especially suitable for patients who do not respond to or cannot tolerate antidepressants, have had a positive prior response to ECT, are delusional or have catatonia or mania, or are in an emergency situation.

Medical status concerns when using ECT include cardiac problems such as a recent myocardial infarction, unstable angina, arrhythmias, congestive heart failure, or hypertension. Pulmonary concerns include COPD and asthma, while gastrointestinal problems such as aspiration or laryngospasm risk factors must be considered. Additionally, musculoskeletal issues such as stress to bones, joints, and vertebrae during treatment and risk of subsequent falls should be weighed. Neurologic conditions including intracranial lesions can increase the risks associated with ECT in older patients.8

The use of ECT may improve depression-impaired cognition but might exacerbate memory loss associated with dementia, especially in the short-term.8 In cases where dementia is present, the patient’s baseline memory should be established. The patient should be monitored throughout treatment, and the frequency of treatments should be decreased if memory loss emerges. Treating patients with unilateral electrode placement is associated with less memory loss than bilateral placement. Clinicians should prepare and reassure the patient and his or her family through education prior to and throughout the course of treatment.

Late-Life Delusional Depression

Delusional depression can be difficult to treat. Although controlled studies for older adults are lacking in this area, a survey9 of expert opinion found that the consensus treatment for older patients with psychotic major depression was an antipsychotic plus an antidepressant (AV 3AV 3).9,10 Another first-line option was ECT, and 1 study11 suggested that ECT may be more effective than medication.

Treatment Adherence

According to expert consensus,10 patients who have had 1 episode of major depression should be treated with antidepressants for at least 1 year; if they have had 2 episodes, they should be treated for 1 to 3 years, and longer than 3 years if they have had 3 or more episodes. The challenge in geriatric depression is to get patients to adhere to treatment.

Many factors influence treatment adherence in older adults, including cognitive impairment, complex dosing regimens, adverse side effects, a lack of understanding of depressive symptoms, cost, lack of family support, and the stigma associated with depression.12 The clinician should anticipate and directly address nonadherence behavior and help the patient develop a method of monitoring his or her own adherence. Other ways to improve treatment adherence include assessing the patient for cognitive or physical impairment, involving family members in the treatment plan, maintaining frequent patient contact, and providing clear and easy-to-understand information regarding the patient’s diagnosis and treatment regimen.


Late-life depression is a common disorder that can severely impact the quality of life for older adults. Physicians should be aware of the varying presentations of depression and aggressively diagnose and treat their older patients with depressive symptoms. While consideration should be given to the individual patient’s medical comorbidities and cognitive status when choosing treatments, psychotherapy, antidepressants, and ECT are all proven therapies for unipolar major depression in older adults.

Drug Names

bupropion (Wellbutrin, Aplenzin, and others), mirtazapine (Remeron and others), nortriptyline (Pamelor, Aventyl, and others), paroxetine (Paxil, Pexeva, and others), and venlafaxine (Effexor and others)


AHCPR=Agency for Health Care Policy and Research, COPD=chronic obstructive pulmonary disease, ECT=electroconvulsive therapy, FDA=US Food and Drug Administration, MAOI=monoamine oxidase inhibitor, SSRI=selective serotonin reuptake inhibitor, TCA=tricyclic antidepressant

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