The depressions of Alzheimer's disease: sorting, pharmacotherapy, and clinical advice

Research describing wide prevalence variation of Alzheimer's disease (AD) and comorbid depression is explained in light of subsyndromal depressions, the use of standardized diagnostic instruments and procedures, and the subcortical and cortical components of mood. There appear to be several "depressions" of AD. Against this backdrop, double-blind, placebo-controlled studies of antidepressant use in AD are reviewed and methodologic problems identified. Evidence for efficacy in controlled trials is weak, but open-label trials are, as expected, more encouraging. The potential efficacy of new agents for the depressions of AD receive comment. A heuristic model makes use of the conclusions developed, the stage of illness, and a preliminary classification scheme for the depressions of AD; this model provides a rational basis for thinking about medication selection for AD depressions. Clinical decisions are illustrated.