Even though their annual sales are recorded in the billions of dollars, antidepressants aren't doing their job. Most people with clinical depression aren't being helped by the drugs, a new study has discovered. Researchers reckon that a brain protein called monoamine oxidase A (MAO-A) is responsible for most cases of clinical depression, and yet they are not affected by the antidepressants. This would explain why earlier studies have discovered the drugs are useless in half of all cases of depression. Early generations of antidepressants developed in the 1970s did target MAO-A proteins, but they were dropped because of adverse reactions, especially with some foods. Since then, antidepressant research has moved away from the MAO-A protein, and has produced drugs that are less effective. Researchers at the Centre for Addiction and Mental Health, who measured the effectiveness of antidepressants with the aid of advanced brain imaging technology, say that time has proved to be a better healer than the drugs, and many people with depression see the production of the protein normalise by itself. (Source: Archives of General Psychiatry, 2009; 66: 1304).