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OBJECTIVE	To review factors influencing placebo response and clinical trial outcome in depression , and suggest ways to optimize trial success in mood disorders .
METHODS	PubMed searches were conducted by cross-referencing the terms depression , depressive with placebo , clinical trial , and clinical trials for studies published in English between 1970 and September 2013 .
METHODS	Relevant abstracts were identified in PubMed , including clinical trials , quantitative studies , and qualitative research .
METHODS	We obtained and reviewed relevant articles and utilized their information to synthesize the present review .
METHODS	Included articles were grouped in the following areas of relevance : ( 1 ) biological validity of illness , ( 2 ) baseline severity of illness , ( 3 ) chronicity of the index episode of depression , ( 4 ) age of participants , ( 5 ) medical and psychiatric comorbidity , ( 6 ) probability of receiving placebo , ( 7 ) use of prospective treatment phases ( lead-in ) ( 8 ) dosing schedule , ( 9 ) trial duration , ( 10 ) frequency of follow-up assessments , and ( 11 ) study outcome measure .
RESULTS	Several key elements emerge as critical to the ultimate success of a clinical trial , including the probability of receiving placebo , study duration , dosing schedule , visit frequency , the use of blinded lead-in phases , the use of centralized raters , illness severity and duration , and comorbid anxiety .
CONCLUSIONS	Our increasing understanding of the placebo response in clinical trials of major depressive disorder lends to a , gradually , more predictable phenomenon and , hopefully , to one that becomes lesser in magnitude and variability .
CONCLUSIONS	Several elements have emerged that seem to play a critical role in trial success , gradually reshaping the design of clinical , translational , as well as mechanistic studies in depression .

