J Clin Psychiatry 2006;67(suppl 6):16-22
© Copyright 2015 Physicians Postgraduate Press, Inc.
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Treatment-resistant depression (TRD) is a common clinical occurrence among patients treated for
major depressive disorder. However, a clear consensus regarding the criteria defining TRD is lacking
in the psychiatric community. Many patients who are considered treatment resistant are actually misdiagnosed
or inadequately treated. Clinicians need to accurately diagnose TRD by examining primary
and secondary (organic) causes of depression and acknowledging paradigm failures that contribute to
a misdiagnosis of TRD. A correct determination of what constitutes TRD requires consensus on criteria
of treatment response (i.e., dose, duration, and compliance) and on the number of adequate trials
required before a patient is determined to be nonresponsive. Additionally, clinical validation of available
staging models needs to be completed. While several studies have identified predictors of nonresponse,
clinical studies investigating the predictors of resistance following the failure of 2 or
more antidepressant trials should be pursued. In managing TRD, 3 pharmacotherapy strategies are in
clinical use: optimization of antidepressant dose, augmentation/combination therapies, and switching
therapies. However, the optimal strategy for treating TRD has yet to be identified. Therefore, further
controlled clinical trials are essential to identify the most effective treatment strategies.