87 Review www.expert-reviews.com ISSN 1473-7175 © 2010 Expert Reviews Ltd 10.1586/ERN.09.138 Major depressive disorder (MDD) is one of the most common diseases with a lifetime preva- lence of 12–25%, a high relapse risk (40% after 2 years) and an often chronic course (in a third of the cases) [1] . It represents an immense psychosocial burden, is related to a shortened lifespan and individual, economical and social impairment [2] . MDDs account for approxi- mately 20–35% of all deaths by suicide [3] . The lower bound of the 20–35% estimate of the prevalence of major depression in suicide is loosely based on a psychological autopsy study [4] where 15% of suicide victims were identiied as having MDD. However, an additional 30% were reported as having ‘atypical depression’. A number of other studies suggest that the preva- lence of major depression in suicide is greater than 30%. Four other available psychological autopsy studies that include samples of suicides from the full range of ages and reliable diagno- ses based on structured interviews [5–8] obtained prevalence estimates of major depression ranging from 30 to 34% of suicides. In addition, several psychological autopsy studies examining more speciic subsamples (e.g., the elderly, adolescents and women) ind even higher prevalence esti- mates. The association between depression and disability has been consistently demonstrated across a wide range of cultures and levels of economic development. Cross-sectional data from two large epidemiologic studies have been used to estimate a monthly productivity loss of approximately US$200–400 for each worker suffering from MDD [9,10] . The epidemiological data along with the economic impact illustrate the particular relevance of MDD as well as the need for adequate treatment of MDD patients. Currently, psychopharmacological as well as psychotherapeutic treatments are the procedures of choice. Recently, brain stimulation procedures have become a focus of interest especially in ‘treatment-resistant depression’ (TRD) that do not resolve after antidepressant drug treatment in adequate doses (or intensity) and for a time suficient for response [11] . Among such procedures are electroconvulsive therapy (ECT) and transcranial magnetic stim- ulation (TMS) as well as neurosurgical treat- ments such as deep-brain stimulation (DBS) and vagus nerve stimulation (VNS). Originally developed as a procedure in refractory epilepsy, VNS has increasingly been used as a treatment option in TRD. Pathophysiology of MDD The initially proposed catecholamine hypoth- esis, which was later extended to the mono- amine hypothesis, proposes a dysfunction in monoamine systems (norepinephrin, serotonin and dopamine), and is based on the effect of Simone Grimm and Malek Bajbouj † † Author for correspondence Charité, CC15, Psychiatry, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany Tel.: +49 30 8445 8601 Fax: +49 30 8445 8233 malek.bajbouj@charite.de www.charite.de/psychiatry Major depressive disorder is a disease with prominent individual, medical and economic impacts. A relevant proportion of depressive patients suffering from a therapy-resistant course are increasingly being treated with antidepressant brain stimulation techniques. One of these interventions is the vagus nerve stimulation that has recently been tested in a number of clinical trials. To date, the acute and long-term ef icacy of vagus nerve stimulation are still under debate. Thus further studies are required, especially since the exact mode of action of vagus nerve stimulation is still not well understood. In this paper we will review the results of existing clinical trials as well as the neurobiological effects measured with neuroimaging, biochemical and electrophysiology approaches. KEYWORDS: brain stimulation • major depression • therapy resistance • vagus nerve • vagus nerve stimulation Eficacy of vagus nerve stimulation in the treatment of depression Expert Rev. Neurother. 10(1), 87–92 (2010) For reprint orders, please contact reprints@expert-reviews.com