Is there a long-term protective effect of mood-altering agents in unipolar depressive disorder?

Major depression is common, often severe, and usually recurrent, and it carries an excess risk of mortality due to medical illness as well as suicide. At referral centers, recurrence risk averages 85% within 2-3 years of full recovery from an acute episode. The natural history of major depression is highly variable, but typically episodes las ca. 6 months, with cycles of ca. 2 years. Yet, most long-term treatment studies are limited to the year or two following recovery from an acute episode. Accordingly, available evidence best supports a relapse-preventing effect of tri-cyclic antidepressants or lithium within the first months after apparent recovery but is less compelling regarding prevention of later recurrences of new episodes. Other treatments have not been evaluated systematically. The hypothesis that bipolarlike, but apparently unipolar, patients might respond selectively to lithium maintenance requires further testing. Knowledge of long-term dose-benefit and dose-risk relationships is starting to emerge for lithium, but these relationships remain inadequately tested for antidepressants. Actual levels of clinical treatment of major depression appear to fall short of the ideal, and much additional research and education is required to improve care in this very common disorder.