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At present it is estimated that nearly 8%-16% of the elderly (aged > 65) living in the community suffer from clinically significant depressive symptoms[1], a harbinger of significant morbidity and early mortality[2]. Older age of a depressed patient is a significant predictor of an unfavourable course with an increased risk of relapse[3], reduced likelihood of treatment response[4,5] and diminished chance selleck chemical of functional recovery[6]. Furthermore, the emergence of treatment resistant depression (TRD) is common among the elderly, with an estimated rate of between 26 and 41 per 100 person-years[7]. An important challenge in optimally treating geriatric depression is the reduced utility of conventional antidepressant treatments. Randomised Controlled Trials (RCTs) of antidepressants reveal Selleckchem EPZ-6438 a smaller size of treatment effect among the elderly compared to the younger age groups. The number needed to treat (NNT) for antidepressant vs placebo use for an acute response goes up steadily with age with estimated numbers of 6 in those aged 65 years[5]. This difference may be related to the differences in the pathophysiology and phenomenology of depression among older people. Whilst depression is mostly a disorder of young adults (peak age of onset in 20 s, with a trend towards more younger age of onset in younger cohorts), late-onset depression (after age 50) has a higher probability of medical comorbidity. There are 2 groups of individuals among those with geriatric depression: one DEF6 with an early onset (