Practical management of treatment-resistant depression.

Patients receiving antidepressant monotherapy may be partially or totally resistant to treatment in 10 to 30 percent of cases. In patients who have experienced only partial treatment results, the clinician should first consider optimizing antidepressant dosage or lengthening therapy. Antidepressant drug substitution should generally be reserved for use in patients who haven't responded at all (nonresponders). Combining two or more antidepressants is generally not recommended, as this approach may obscure adequate monotherapy evaluation and lead to significant adverse effects or drug-drug interactions. Use of electroconvulsive therapy is recommended in patients with psychotic and severe refractory depression. Augmentation therapy is often efficacious in patients who exhibit a partial antidepressant response. Lithium and thyroid hormone have been the most extensively studied augmentative agents but, more recently, pindolol and buspirone have also been used for this purpose.