Depressive breakthrough.

Controlled studies of continuation and maintenance pharmacotherapy have consistently shown the advantage of drug therapy over placebo for the prevention of relapses and recurrences, particularly when antidepressant medications are maintained at the full dose required initially to establish remission. Nevertheless, controlled and observational studies indicate substantial rates of relapse and recurrence despite long-term treatment. Although depressive breakthrough is a common clinical problem, few uncontrolled studies and no controlled trials are available on management of depressive breakthrough. Three principal pharmacologic strategies seem to be (1) increasing dose, (2) adding another agent, and (3) switching antidepressants. Controlled studies of long-term treatment are needed to identify the optimal nature and sequence of approaches for re-emergent depression and to determine what symptom severity and duration should prompt the initiation of treatment.