Vol 8, No 2 - Depression in Medicine
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epression is an incapacitating disorder with a lifetime prevalence of 16%,1 with a female-to-male ratio of about 5:2. Research is beginning to allow us to fully grasp the complexity of factors—personal, genetic, bio- logical, societal, and environmental—which are involved. Several efficient treatments and strategies exist, among which antidepressant drugs are a main choice.Although the criteria for choosing the best strategy remain empir- ical—there is some indication that the efficacy of antide- pressants is comparable between and within classes— most patients are best treated with a combination of 1 9 1 P h a r m a c o l o g i c a l  a s p e c t s D Copyright © 2006 LLS SAS.  All rights reserved www.dialogues-cns.org Treatments in depression Fabrice Duval, MD; Barry D. Lebowitz, PhD; Jean-Paul Macher, MD Keywords: antidepressants; major depression; kindling; neuroplasticity; mana- gement strategy; treatment predictor Author affiliations: Centre Hospitalier, Rouffach, France (Fabrice Duval, Jean- Paul Macher); University of California, San Diego, California, USA (Barry D. Lebowitz) Address for correspondence: Dr Fabrice Duval, BP 29, 68250 Rouffach, France (e-mail: f.duval@ch-rouffach.fr) Major depression is believed to be a multifactorial disorder involving predisposing temperament and personality traits, exposure to traumatic and stressful life events, and biological susceptibility. Depression, both unipolar and bipolar, is a “phasic” disease. Stressful life events are known to trigger depressive episodes, while their influence seems to decrease over the course of the illness. This suggests that depression is associated with progressive stress response abnormalities, possibly linked to impairments of structural plasticity and cellular resilience. It therefore appears cru- cial to adequately treat depression in the early stages of the illness, in order to prevent morphological and functional abnormalities. While evidence suggests that a severely depressed patient needs antidepressant drug therapy and that a non-severely depressed patient may benefit from other approaches (ie, “nonbiological”), little research has been done on the effectiveness of different treatments for depression. The assertion that the clinical efficacy of antide- pressants is comparable between the classes and within the classes of those medications may be true from a statisti- cal viewpoint, but is of limited value in practice. The antidepressant drugs may produce differences in therapeutic response and tolerability. Among the possible predictors of outcome in depression treatment, those derived from clin- ical assessment, neuroendocrine investigations, polysomnographic sleep parameters, genetic variables, and brain imag- ing techniques have been extensively studied. This article also reviews therapeutic strategies used when initial treat- ment fails, and describes briefly new concepts in antidepressant therapies such as the regulation of disturbances in circadian rhythms. The treatment of depressive illness does not stop with treatment of acute episodes, and has to be envisaged as a continuous therapeutic intervention, of which we are still not able to determine the optimal duration of treatment and the moment that it should be ceased.   © 2006, LLS SAS Dialogues Clin Neurosci. 2006;8:191-206.