Psychosurgery and deep brain stimulation as ultima ratio treatment for refractory depression

For decades, the most severe, protracted and therapy-resistant forms of major depression have compelled clinicians and researchers to look for last resort treatment. Early psychosurgical procedures were hazardous and often associated with severe and persistent side effects including avolition, apathy and change of personality. With the introduction of psychopharmacological treatments in the 1950s, the frequency of ablative procedures declined rapidly. The past decade, however, has witnessed the resurgence of surgical strategies as a result of refined techniques and advances such as high frequency stimulation of deep brain nuclei. Recent data suggest that the overall effect of high frequency stimulation lies in the functional inhibition of neural activity in the region stimulated. Contrary to other psychosurgical procedures, high frequency stimulation reversibly modulates targeted brain areas and allows a postsurgical adaption of the stimulation parameters according to clinical outcome. With increased understanding of the brain regions and functional circuits involved in the pathogenesis of psychiatric disorders, major depression has emerged as a target for new psychosurgical approaches to selectively and precisely modulate neural areas involved in the disease process. Recent studies of minimally intervening procedures report good clinical outcome in the treatment of therapy-resistant forms of major depression. High frequency stimulation was successfully applied in several small samples of patients with treatment-resistant depression when the stimulation focused on different areas, e.g., nucleus accumbens, the lateral habenula or cortical areas. Nevertheless, the reticence toward psychosurgery, even for those patients suffering from the most debilitating forms of depression, still prevails, even though recent studies have shown significant improvement in terms of quality of life with the limitation that the number of treated cases has been small. In any event, valid and unambiguous criteria for patient eligibility have yet to be refined and standardized. In this review, we suggest possible standard criteria for the application of deep brain stimulation on patients suffering from otherwise treatment-resistant depression.