Psychopharmacological approaches to prevention and treatment of relapse and recurrence

Preventing a reemergence of depressive symptoms is the primary goal in the long-term pharmacotherapy of chronic depression. Nevertheless, return of clinically significant depression occurs all too commonly both during and following treatment. Depressive episodes that reappear within 6 months of acute response are called relapses and those that occur after 6 months are called recurrences [1]. Theoretically, relapses are considered a return of the original episode, whereas recurrences represent a new episode. Although these distinctions are based on limited data, the phases of treatment to prevent relapse and recurrence have been differentiated correspondingly into continuation and maintenance phases, respectively. Without long-term antidepressant treatment, depressive relapses or recurrences occur in 50–80% of patients [1–6]. Double-blind discontinuation studies reveal that antidepressants lower the risk of relapse and recurrence, and they have repeatedly been shown to be superior to placebo substitution [2,7–10]. Nonetheless, even while taking longterm antidepressants for prophylaxis, observational studies have shown that within 1–5 years after an acute response, 20–80% of patients develop another depressive episode [6,8,11–19]. Estimated rates of relapse and recurrence vary because of factors related to study design (controlled vs observational; flexible vs fixed dosing; duration of follow-up; definitions of relapse/recurrence) and patient samples (degree of recurrence/chronicity; outpatient vs inpatient; primary vs specialty care settings; demographic/clinical factors). A succinct term for relapse or recurrence during long-term antidepressant treatment is depressive breakthrough. In this chapter, we review existing guidelines for longer term treatment of depression for prevention of relapse and recurrence, current knowledge concerning the use of contemporary agents for continuation and maintenance treatment, the evolving appreciation for the clinical phenomenon of depressive breakthrough, and psychopharmacological strategies for treatment of breakthrough.