Geriatric depression: brain imaging correlates and pharmacologic considerations.

The clinical approach to geriatric major depression involves a variety of special etiopathophysiologic, pharmacokinetic, and pharmacodynamic considerations. In regard to pathophysiology, modern brain imaging and postmortem assessments are elucidating neuropathologic changes in elderly depressives that challenge the notion that geriatric depression is simply a functional brain disorder. These data suggest (but do not yet establish) that many patients who experience depression onset at a late age may acquire affective disease on an arteriosclerotic basis. In contrast, elderly depressives who experience depression onset at an early age are more likely to have acquired depression due to genetic factors but may nevertheless develop degenerative neuropathologic changes over time. The presence of these neuropathologic changes appears to increase elderly patients' risk for developing the adverse central nervous system (CNS) effects of antidepressant treatments. They thereby add another level of complexity to the management of an age group in which pharmacokinetic and pharmacodynamic changes already contribute to the likelihood of adverse drug reactions. Fortunately, the last decade of antidepressant drug development has produced several new agents (including the serotonin selective reuptake inhibitors and more recently, venlafaxine and nefazodone) with substantially reduced CNS and cardiovascular toxicity that facilitate effective treatment of geriatric depression.