Onset, time course and trajectories of improvement with antidepressants.

There is still considerable controversy about the onset and time course of improvement with antidepressants in the treatment of major depressive disorder. Previous studies suggested a delayed-onset hypothesis with therapeutic improvement taking several weeks, but recent meta-analyses have shown support for earlier onset of improvement within the first week or two of treatment. This paper briefly reviews the evidence, focused on antidepressant studies published since 2006, for early onset of improvement within the first 2 weeks of treatment. A PubMed electronic search was conducted with selection of relevant studies from 2007 to March 2012. With the caveat of methodological limitations, results from randomized clinical trials, meta-analyses and naturalistic studies consistently show that: (1) antidepressants in general have early onset of improvement, (2) some antidepressants, including the novel mechanism agent, agomelatine, are associated with early improvement in both core and specific symptoms such as anhedonia and sleep-wake disturbances, and (3) early improvement predicts sustained response and remission. Use of newer statistical methods to examine individual response trajectories may address some of the methodological limitations of previous studies. The predictive value of early improvement has important clinical relevance for antidepressant treatment. Measurement-based assessment for response should occur earlier and more frequently. A lack of improvement (defined as ≤20% reduction from baseline in scores on a depression rating scale) at 2-3 weeks after initiation of an antidepressant should prompt the clinician to consider a change in management.