Treatment Resistant Depression

Most of the literature on Treatment Resistant Depression (TRD) has based its definition of resistance on the failure to respond to antidepressant drug treatment of adequate dose and duration. The prevalence of TRD is lowest in primary care settings and progressively increases in outpatient psychiatry settings, inpatient psychiatric settings, and academic/tertiary care settings. Strategies available for the treatment of TRD include optimization, substitution or switching, combination, and augmentation therapies. Currently there are no clear guidelines on when to substitute, combine, or augment therapies in the treatment of patients with TRD. Some new and novel therapies that show promise for the future include addition of an atypical antipsychotic to the initial antidepressant; newer pharmacologic interventions; and non-pharmacologic therapies such as vagus nerve stimulation (VNS), repetitive transcranial magnetic stimulation (rTMS), and deep brain stimulation (DBS). The newer models of interpersonal, cognitive, and behavioral therapies offer structured, pragmatic methods to work with such difficult patients. Guidelines for psychotherapeutic intervention for TRD suggested that the therapy should be collaborative and centered on the goal of teaching new skills to improve coping with a chronic illness. A better understanding of the many facets of the etiology of TRD as well as the availability of new and effective therapies hopefully will decrease the morbidity and mortality associated with this condition.