AREAS OF UNCERTAINTY
Randomized trials are needed to evaluate the efficacy and risks of many treatments currently used for late-life depression. For many antidepressants, data on efficacy and safety in older populations are scarce or absent, so treatment decisions are often guided by data from younger adults. However, there may be increased risks specific to older populations.20 Data on long-term pharmacotherapy and psychotherapy maintenance strategies in older populations are also limited.
It is unclear how best to address cognitive deficits in patients with late-life depression. Cognitive impairment is predictive of a poor response to antidepressants38,39; even with remission of depression, deficits may persist and signal a high risk of dementia. In a blinded, placebo-controlled trial of donepezil as an adjunct to antidepressant therapy for the maintenance treatment of depression, the donepezil group had, at best, modest and transient improvement in cognitive measures over a 2-year period and a significantly higher risk of depression recurrence50; post hoc analyses suggested that these effects were limited to patients with concomitant mild cognitive impairment. Neither memantine, a drug approved for the treatment of Alzheimer's disease, nor stimulants such as methylphenidate have been shown to have cognitive benefits in patients with late-life depression.
GUIDELINES
The recommendations provided here are consistent with American Psychiatric Association practice guidelines for the treatment of major depressive disorder, which include recommendations for the treatment of older adults.51 These guidelines highlight the need for careful evaluation of suicide risk and coexisting medical conditions in this population.
CONCLUSIONS AND RECOMMENDATIONS
The patient described in the vignette is having a first episode of depression and also has some memory problems. It is crucial to ask about suicidal thoughts, alcohol use, and coexisting medical illnesses. First-line treatment could involve either pharmacotherapy or psychotherapy (in particular, problem-solving therapy, because it has been shown to benefit depressed patients who also have cognitive impairment); the choice would depend on the patient's preference and the availability of psychotherapy. If medication were used, the recommended initial therapy would be administration of an SSRI, starting at a low dose (e.g., sertraline at a daily dose of 25 mg) in order to assess the patient for side effects and then increasing to a minimum therapeutic dose (50 mg daily in the case of sertraline). Higher doses may be needed for maximal efficacy (e.g., 100 mg or more of sertraline daily), with close attention to side effects. If the depressive symptoms are not sufficiently reduced, I would consider a change to an SNRI, such as venlafaxine. Screening for cognitive deficits should be performed and formal neuropsychological testing should be considered if cognitive symptoms persist or worsen despite antidepressant therapy.