A systematic review of 44 clinical studies published between January 1980 and April 2011 examined the comparative effectiveness, benefits, and adverse effects of interventions for adults and adolescents with major depressive disorder (MDD) who have an unsatisfactory response to treatment with a selective serotonin-reuptake inhibitor (SSRI). The review also compared recommendations from 27 Clinical Practice Guidelines (CPGs) published from January 2004 to April 2011.