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 .