Clinical application of time-dependent sensitization to antidepressant therapy

1. A number of animal studies have shown that the actions of numerous drugs can grow or sensitize with the passage of time following even a single treatment, to achieve results equal to or greater than those seen after chronic administration. 2. Our laboratory earlier proposed that this principle might be applied to the treatment of human disorders. It was suggested that the same results might be achieved by giving drugs once every one or two weeks rather than daily, or, even more likely, several-times-daily. 3. Here the authors review the clinical literature relevant to that hypothesis, as it relates to antidepressant therapies. 4. The evidence uniformly supports our earlier thesis that the therapeutic influence of antidepressants would grow with the passage of time, even as their pharmacokinetic actions are declining.