Treatment algorithms in treatment-resistant depression

When faced with a patient having treatment-resistant depression, it is essential to maintain a systematic approach to diagnosis and treatment: 1. Consider the presence of comorbid medical or psychiatric illness that may contribute to or cause the refractory state 2. Determine the affective subtype of depression (e.g., unipolar vs. phenotypic variant of bipolar depression) 3. Ensure the presence of adequate antidepressant dosage, plasma concentrations (where applicable), and duration of treatment 4. Apply systematic treatment algorithms, which means (1) initiate the most efficacious "first-line" therapy for a specific depressive subtype (even if that is an MAOI) and (2) initiate augmentation strategies in a systematic fashion. Augmentation strategies should be initiated only after first reviewing prior therapy, considering available treatment alternatives, and examining the relative risk:benefit ratio for each treatment option in the current clinical context. Following these guidelines should prevent the development of "therapeutic nihilism" in both the patient and physician, as well as enhance the ultimate treatment outcome for patients with treatment-resistant depression.