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Updated: Apr 6, 2026

Vagus Nerve Stimulation As an Adjunctive Neurostimulation Tool in Treatment-resistant Depression
Published on: January 7, 2019
Nonconvulsive Electrotherapy for Treatment Resistant Unipolar and Bipolar Major Depressive Disorder: A
William T Regenold1, Robert J Noorani2, Deborah Piez1
1Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Background:
Electroconvulsive therapy (ECT) is the most effective therapy for treatment resistant major depressive disorder (TRD); however, some individuals with TRD refuse ECT over concern about adverse cognitive effects. Clinical observation of two patients with TRD who had a therapeutic response to intended ECT despite having only one or no seizure suggested that nonconvulsive electrical stimulation may be effective in some patients.
Objective/Hypothesis:
This study tested the hypothesis that electrical brain stimulation applied like standard ECT, but below seizure threshold, can have therapeutic effects on TRD with fewer adverse cognitive effects.
Methods:
Thirteen outpatients with TRD (6 unipolar, 7 bipolar) who refused ECT participated in this open label adjunctive treatment study of nonconvulsive electrotherapy (NET) at the University of Maryland Medical Center. Brief pulse bifrontal electrical stimulation was given thrice weekly with a Thymatron System IV Integrated ECT Instrument.
Results:
Seizure-free data were obtained from 11 of 13 subjects. Group mean Hamilton Depression Rating Scale 17-item version scores declined significantly (P = 0.001) from 20.3 to 8.6. Response and remission rates were 73% (8) and 55% (6), respectively. Cognitive testing using the Mini-Mental State Exam and the Autobiographical Memory Inventory-Short Form did not show declines typically observed with ECT.
Conclusions:
The therapeutic effect of NET on TRD was similar to that of ECT. Serious adverse effects and adverse cognitive effects were not observed. These results challenge the widespread belief that a seizure is necessary for the antidepressant effect of ECT and merit further investigation to determine whether NET is a viable alternative to ECT in some patients with TRD. Clinical trial posted on www.clinicaltrials.gov, identifier: NCT01065597.
Related Concept Videos
Electroconvulsive Therapy
Antidepressant Drugs: MAOIs and Other Agents
Mania and Antimanic Drugs: Overview
Bipolar Disorder
Depressive Disorders: MDD and Dysthymia
Antidepressant Drugs: Tricyclics, SSRIs, and SNRIs

