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Expert Rev Neurother. 2009 Jul;9(7):975-84. doi: 10.1586/ern.09.53.

Strategies to enhance the therapeutic efficacy of antidepressants: targeting residual symptoms.

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Department of Psychiatry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9119, USA.


Major depressive disorder (MDD) is an illness of great morbidity that affects many people across the world. The current goal for treatment of MDD is to achieve remission (i.e., no depressive symptoms). However, despite scientific advances in the treatment for MDD, antidepressants as first-line agents yield only modest remission rates. In fact, a recent study indicated that only one out of three subjects who received a standard, first-line antidepressant attained remission. Not achieving remission from depressive symptoms increases the risk of a more chronic and debilitating course of illness with frequent recurrences. Although a number of reasons contribute to these modest outcomes, the presence of residual symptoms is a major problem. Residual symptoms are defined as symptoms that linger despite an adequate dose and duration of an antidepressant medication. This article reviews the prevalence and clinical impact of common residual symptoms and discusses the utility of aggressively addressing residual symptoms to enhance the efficacy of antidepressant medications.

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