Depression, Depressionen

Communications

Vagus Nerve Stimulation (VNS) for Treatment Resistant Depressions: A Multicenter Study*

A. John Rush, Mark S. George, Harold A. Sackeim, Lauren B. Marangell, Mustafa M. Husain, Cole Giller, Ziad Nahas, Stephen Haines, Richard K. Simpson, Jr., and Robert Goodman

Background: Vagus Nerve Stimulation (VNS) delivered by the NeuroCybernetic Prosthesis (NCP) System was examined for its potential antidepressant effects.

Methods: Adult outpatients (n = 30) with nonpsychotic, treatment-resistant major depressive (n = 21) or bipolar 1 (n = 4) or II (n = 5; depressed phase) disorders who had failed at least two robust medication trials in the current major depressive episode (MDE) while on stable medication regimens completed a baseline period followed by NCP System implantation. A 2-week, single-blind recovery period (no stimulation) was followed by 10 weeks of VNS.

Results: In the current MDE (median length = 4. 7 vears), patients had not adequately responded to two (n = 9), three (n = 2), four (n = 6), or five or more (n = 13) robust antidepressant medication trials or electroconvulsive therapy (n = 17). Baseline 28-item Hamilton Depression Rating Scale (HDRS₂₈₎ scores averaged 38.0. Response rates >50% reduction in baseline scores) were 40% for both the HDRS₂₈ and the Clinical Global Impressions - Improvement index (score of 1 or 2) and 50% for the Montgomery - Asberg Depression Rating Scale. Symptomatic responses (accompanied by substantial functional improvement) have been largely sustained during long term follow-up to date.

Conclusions: These open trial results suggest that VNS has antidepressant effects in treatment-resistant depressions. Biol Psychiatry 2000;47:276‐286 2000 Sociely of Biological Psychiatry

Key Words: Vagus Nerve Stimulation (VNS), treatment resistant depression, bipolar disorder, electrical stimulation

*See accompanying Editorial, in this issue.

From the Departments of Psychiatry and Neurosurgery, University of Texas Southwestern Medical Center, Dallas (AJR, MMH. CG); the Departments of Psychiatry, Radiology. and Neurosurgery, Medical University of South Caro lina (MSG. ZN, SH) and Ralph H. Johnson Veterans Hospital (MSG), Charleston, South Carolina; the Departments of Psychiatry, Radiology, and Neurosurgery, Columbia College of Physicians and Surgeons, and New York State Psychiatrie Institute. New York (HAS. RG); and the Departments of Psychiatry and Neurosurgery, Baylor College of Medicine. Houston. Texas (LBM, RKS).

Address reprint requests to A. John Rush. Department of Psychiatry. University of Texas Southwestern Medical Center, 5323 Harry Hines BIvd., DalIas, TX. 75235-9086.

Received November 12, 1999; revised December 6, 1999; accepted December 6, 1999.

Introduction

Depression is a prevalent, disabling, and often chronic or recurrent psychiatric condition costing the United States economy more than $40 billion per year, of which $12.4 billion are direct treatment costs (Greenberg et al 1993). The 6-month prevalence of depression in the general population is about 5% (Depression Guideline Panel 1993a). Three hundred forty million people world wide, 18 million of them in the United States, suffer from depression at any one time. Further, depressive episodes usually recur over time, with the risk for further episodes proportional to the number of prior episodes. From 5% to 15% of major depressive episodes last longer than 2 years. Up to 1.5% of the general population suffer chronic or severe depressions (Depression Guideline Panel 1993a; Lopez and Murray 1998). Up to 15% of all people with severe depressions requiring hospitalization eventually commit suicide (Depression Guideline Panel 1993b; Guze and Robins 1970).

Treatment for depression aims at achieving complete symptom remission and complete restoration of day-to day function, as well as prevention of relapses (return of current episode) and recurrences (new episodes). Numerous antidepressant medications and several forms of empirically documented, time-limited psychotherapies are available. Depression is typically treated with medication, psychotherapy, or a combination of both. Different patients appear to respond to different treatments. A patient who does not respond to one treatment may well respond to another (Crismon et al 1999; Depression Guideline Panel 1993b; Thase and Rush 1995).

At least 10% to 20% of all depressed patients do not have satisfactory sustained responses to present treatments.¹ Treatment resistance may increase with increasing numbers of episodes or increasing episode duration (Depression Guideline Panel 1993b; Thase and Rush 1995). About 100,000 patients annually, most of whom have treatment-resistant depression, receive a course of electroconvulsive therapy (ECT; American Psychiatric Association Committee on ECT, in press; Olfson et al 1998).

¹Perhaps 1‐4% of patients with major depressive episodes attain the level of treatment resistance required of this research sample.