Psychological Medicine

Original Articles

Vagus nerve stimulation for depression: efficacy and safety in a European study

T. E. Schlaepfera1a2a3 c1, C. Fricka1a2, A. Zobela2, W. Maiera2, I. Heusera4, M. Bajbouja4, V. O'Keanea5, C. Corcorana5, R. Adolfssona6, M. Trimblea7, H. Raua8a9, H.-J. Hoffa8, F. Padberga10, F. Müller-Siechenedera10, K. Audenaerta11, D. Van den Abbeelea11, K. Matthewsa12, D. Christmasa12, Z. Stangaa1 and M. Hasdemira13

a1 Department of Psychiatry, University Hospital, Bern, Switzerland

a2 Department of Psychiatry and Psychotherapy, University Hospital, Bonn, Germany

a3 Departments of Psychiatry and Mental Health, The Johns Hopkins University, Baltimore, MD, USA

a4 Psychiatrische Klinik der FU Berlin, Berlin, Germany

a5 Beaumont Hospital, Department of Psychiatry, Dublin, Ireland

a6 University Hospital Umea, Umea, Sweden

a7 National Hospital for Neurology and Neurosurgery, Department of Neuropsychiatry and Neurology, London, UK

a8 Evangelisches Krankenhaus Bielefeld, Bielefeld, Germany

a9 Alcohol Rehabilitation Clinic, Wilhelmsdorf, Germany

a10 Departments of Psychiatry and Psychotherapy, Ludwig-Maximilian-University, Munich, Germany

a11 University Hospital Gent, Gent, Belgium

a12 Ninewells Hospital and Medical School, Department of Psychiatry, Dundee, UK

a13 Lindenhof Hospital, Department of Neurosurgery, Bern, Switzerland


Background Vagus nerve stimulation (VNS) therapy is associated with a decrease in seizure frequency in partial-onset seizure patients. Initial trials suggest that it may be an effective treatment, with few side-effects, for intractable depression.

Method An open, uncontrolled European multi-centre study (D03) of VNS therapy was conducted, in addition to stable pharmacotherapy, in 74 patients with treatment-resistant depression (TRD). Treatment remained unchanged for the first 3 months; in the subsequent 9 months, medications and VNS dosing parameters were altered as indicated clinically.

Results The baseline 28-item Hamilton Depression Rating Scale (HAMD-28) score averaged 34. After 3 months of VNS, response rates (50% reduction in baseline scores) reached 37% and remission rates (HAMD-28 score <10) 17%. Response rates increased to 53% after 1 year of VNS, and remission rates reached 33%. Response was defined as sustained if no relapse occurred during the first year of VNS after response onset; 44% of patients met these criteria. Median time to response was 9 months. Most frequent side-effects were voice alteration (63% at 3 months of stimulation) and coughing (23%).

Conclusions VNS therapy was effective in reducing severity of depression; efficacy increased over time. Efficacy ratings were in the same range as those previously reported from a USA study using a similar protocol; at 12 months, reduction of symptom severity was significantly higher in the European sample. This might be explained by a small but significant difference in the baseline HAMD-28 score and the lower number of treatments in the current episode in the European study.

(Received April 12 2007)

(Revised December 04 2007)

(Accepted December 10 2007)

(Online publication January 04 2008)


c1 Address for correspondence: T. E. Schlaepfer, M.D., Department of Psychiatry/University Hospital, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. (Email: