finding. Limitations and strategies Among individuals treated with a given antidepressant, between 30% and 50% do not show a response. Approximately one-third of people achieve a full remission, one-third experience a response, and one-third are non-responders. Partial remission is characterized by the presence of poorly defined residual symptoms. These symptoms typically include depressed mood, anxiety, sleep disturbance, fatigue, and diminished interest or pleasure. It is currently unclear which factors predict partial remission. However, it is clear that residual symptoms are powerful predictors of relapse, with relapse rates three to six times higher in people with residual symptoms than in those, who experience full remission. In addition, antidepressant drugs tend to lose efficacy throughout longterm maintenance therapy. According to data from the Centers for Disease Control and Prevention, less than one-third of Americans taking one antidepressant medication have seen a mental health professional in the previous year. Several strategies are used in clinical practice to try to overcome these limits and variations. They include switching medication, augmentation, and combination. There is controversy amongst researchers regarding the efficacy and risk-benefit ratio of antidepressants. Although antidepressants consistently out-perform a placebo in meta-analyses, the difference is modest and it is not clear that their statistical superiority results in clinical efficacy. The aggregate effect of antidepressants typically results in changes below the threshold of clinical significance on depression rating scales. Proponents of antidepressants counter that the most common scale, the HDRS, is not suitable for assessing drug action, that the threshold for clinical significance is arbitrary, and that antidepressants consistently result in significantly raised scores on the mood item of the scale. Assessments of antidepressants using alternative, more sensitive scales, such as the MADRS, do not result in marked difference from the HDRS and likewise only find a marginal clinical benefit. Another hypothesis proposed to explain the poor performance of antidepressants in clinical trials is a high treatment response heterogeneity. Some patients, that differ strongly in their response to antidepressants, could influence the average response, while the heterogeneity could itself be obscured by the averaging. Studies have not supported this hypothesis, but it is very difficult to measure treatment effect heterogeneity. Poor and complex clinical trial design might also account for the small effects seen for antidepressants. The randomized controlled trials used to approve drugs are short, and may not capture the full effect of antidepressants. Additionally, the placebo effect might be inflated in these