Methodological approaches to the long-term study of antidepressants.

It has long been known that most patients with bipolar disorder have a course marked by multiple recurrence of major depressive and manic episodes. More recently, many epidemiological studies have shown that at least 50% of unipolar depressive patients have one or more subsequent episodes of depression in their lifetimes. Likewise, relapse following successful short-term treatment of depression is so common that it is now recommended to prolong treatment in the form of maintenance pharmacotherapy. Interest in preventing the recurrence of depression has been stimulated by the results from long-term trials involving antidepressant drugs and lithium. However, these pharmacological studies suffer somewhat from methodological deficits, making difficult any clear and complete interpretation of their results. While some methodological recommendations have now been established to compensate for previous deficits (eg, definition of relapse and recurrence, duration of acute and maintenance treatments, statistical analysis of efficacy), unfortunately, many key points still remain to be resolved (eg, selection of patients, dosage in maintenance and prophylactic phases, maximum length of a course of treatment, etc).