Background: The failure to achieve remission for patients with Major Depressive Disorder (MDD) represents a major public health concern. Inadequately treated depression is associated with higher rates of relapse, poorer quality of life, deleterious personal and societal economic ramifications, as well as increased mortality rates. Unfortunately, only a minority of patients achieves this goal with initial antidepressant treatment and by convention, failure to achieve response after two adequate trials of antidepressant therapy defines "Treatment Resistant Depression" (TRD). Furthermore, results from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) group of studies suggest that approximately 50% of "real world" patients who meet criteria for MDD fail to achieve remission, even after four carefully monitored sequenced treatments.
Methods: Given these limitations of existing antidepressant medications alone and in combination, together with improved understanding of the neural circuitry of depression, it is not surprising that there is a renewed interest in neuromodulation strategies for TRD.
Results: The purpose of this article is to review the evidence for the inclusion of various non-pharmacological, neuromodulatory strategies for TRD. Specifically, information regarding the mechanism, tolerability and efficacy of electroconvulsive therapy (ECT), magnetic seizure therapy (MST), repetitive transcranial magnetic stimulation (rTMS), vagal nerve stimulation (VNS), and deep brain stimulation (DBS) in ameliorating TRD will be presented.
Conclusions: Although these treatments are at various stages of clinical development, they represent a new frontier in expanding the treatment options available for individuals with TRD, as well as contributing to a better understanding the neurobiology of depressive disorders.