R E V I E W Combination/augmentation strategies for improving the treatment of depression Chantal Moret NeuroBiz Consulting & Communications, Castres, France Correspondence: Chantal Moret NeuroBiz Consulting & Communications, Les Grèzes, La Verdarié, 81100 Castres, France Tel +33 563 590 735 Fax +33 563 590 735 Email chantal.moret@neurobiz.com Abstract: Depression is a common and debilitating condition, with considerable impact for depressed individuals and a heavy burden for society. In spite of its prevalence, depression is underrecognized and under- or inappropriately treated. In spite of the large number of antidepressants available at the present time, they are far from ideal and all show a similar slow, and frequently, incomplete response. Thus, the need for new and better compounds is as urgent and compelling as ever. While waiting for the panacea of future antidepressants, clinicians have developed a variety of associations of several antidepressants or an antidepressant with a second different agent. This article reviews the various strategies adopted by clinicians in the hope of increasing the response rate of current antidepressants to obtain full remission and/or to overcome treatment-resistant depression. Keywords: depression, combination, augmentation, treatment-resistance Introduction Although depression affects a substantial proportion of the population (Kessler et al 2003), this disease is underrecognized and, if diagnosed (APA 1994), is still frequently inadequately or inappropriately treated. Because of the high prevalence and chronicity of depression, a complete antidepressant response remains an important objective for clinicians and is still a key target for new drug development (Andrade et al 2003; Greenberg et al 2003). “Response” of a depressed patient to treatment is defined as at least a 50% reduction in depressive symptoms evaluated on a standard instrument, such as the Hamilton Depression Rating Scale (HAM-D) or Montgomery-Asberg Depression Rating Scale (MADRS) (Frank et al 1991). Although clearly the symptoms of a “responder” are improved, he or she is not “cured” or in “remission”, which is a total absence of all symptoms of depression. Operationally, this is usually defined as a level of depressive symptoms that fall below a threshold value such as a score of ≤ 7 on the 17-item HAM-D as recommended by Frank et al (1991). It is generally accepted that about two thirds of patients treated for depression will respond to some extent albeit after several weeks (2–8 weeks) (Bosker et al 2004) and a third will not respond at all (Pérez et al 2001). Full remission, when it occurs (in about 30%–50% of treated patients), can take 4–6 weeks up to months to achieve (Rush and Trivedi 1995; Ferrier 1999). Despite the diversity of their mechanisms of action, all current antidepressants produce approximately the same final rates of response and remission (Artigas et al 2002). These figures speak for themselves, and the need for strategies to increase the response rate of patients and to obtain full remission in as many patients as possible is clear. Neuropsychiatric Disease and Treatment 2005:1(4) 301–309 © 2005 Dove Medical Press Limited. All rights reserved 301