Mood disorders, particularly treatment-resistant depression, remain a significant clinical and public health challenge with high levels of disability, social and economic costs. Despite advances in pharmacological and psychological management, depression remains difficult to treat effectively and vies with cardiac illness as being the most disabling in terms of economic costs to society and level of disability. In terms of outcome unipolar depression is associated non-recovery and chronicity of symptoms (10-15%), recurrence (>50%), on-going residual symptomatology, unnatural death (6-8%) and social disability. Recent studies have also shown similar outcomes in first-episode and primary care cohorts even with intensive treatment.