Rational polypharmacy in the treatment of mood disorders

Increasing awareness of treatment resistance and the emergence of tolerance on once effective medications have facilitated acceptance of a variety of novel drug combination treatment strategies. Although clinical practice is based for the most part on a literature that is still seriously lacking in well-controlled and methodologically rigorous studies, the risk-benefit ratio in most cases seems acceptable if a clear understanding of the possible therapeutic and adverse interactions on the part of both the physician and the patient prevails. Historically, drug combinations have emerged out of serendipity, but increasingly, theories of complimentary drug action serve a heuristic propose in guiding clinical research efforts, and in testing the purposed mechanisms of actions for each of the drugs separately.