The biology of recurrence: new directions for the pharmacologic bridge.

Recurrence is a fundamental reality of the major affective disorders and must be considered in treatment planning. Historically, however, information regarding the pathophysiology and neurobiology of affective disorders was not gained from studies on recurrence, but rather from research utilizing drugs classified on the basis of their effect on acute manic and/or depressive states. Though such cross-sectional strategies were critical in developing the original amine hypotheses, they also were inherently limited. Today, accumulating information regarding differential drug effects on cycle length calls for reexamining the pharmacologic bridge from the perspective of the nascent neurobiology of recurrence of affective disorders. This presentation considers the array of drugs now used in treating mood disorders and reviews recent data relating to the role of acute and maintenance treatments on the occurrence of manic and hypomanic reactions in bipolar patients. In addition, emerging data on the impact of longitudinal treatments on the natural course of bipolar illness are used to develop a model for examining the effects of treatment on recurring unipolar illness.