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Recovery, complete remission of symptoms, and a return to baseline psychosocial function, should be the goal of therapy. Poor response to adequate antidepressant treatment has been termed treatment resistant depression (TRD). Issues such as adherence, missed diagnosis of psychotic depression, bipolar disorder, or comorbid anxiety must be investigated as reasons why patients have not responded to initial therapeutic strategies. Beyond ensuring optimal use of the index antidepressant, treatment strategies for TRD include switching to another antidepressant, and augmentation or combination with two or more agents. Since little comparative data exist it is important to consider side\u2010effect burden, partial response, and previous medication history when deciding between strategies. In patients with TRD, adding or augmenting with lithium, tri\u2010iodothyronine or atypical antipsychotics have demonstrated benefits. Augmentation with atypical antipsychotics, including risperidone, olanzapine, ziprasidone, and quetiapine, show promising results in terms of improving remission rates. Other interventions, including non\u2010pharmacologic strategies and investigational physical treatments, have demonstrated some benefits, but availability and patient preference should also be considered. With today's therapeutic alternatives, full remission of depression is an attainable goal. 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