Major depression is the leading cause of disability-related health loss in the western world with an annual economic cost to New Zealand of $2 billion. For one third of people with major depression current drug treatments are ineffective, and the development of new treatments is hampered by our lack of understanding of the biological basis of depression. In this study we will conduct brain imaging studies of two medicines that have been previously shown to be clinically effective as new rapid-acting antidepressants. To determine how these drugs work as antidepressants, we will use advanced brain imaging technologies to measure brain activity before and after giving patients the medicines. The results of our studies will substantially increase our understanding of the biological basis of depression and aid the future development of new treatment approaches.