The Application of Vagus Nerve Stimulation and Deep Brain Stimulation in Depression

Abstract

Despite the progress in the pharmacotherapy of depression, there is a substantial proportion of treatment-resistant patients. Recently, reversible invasive stimulation methods, i.e. vagus nerve stimulation (VNS) and deep brain stimulation (DBS), have been introduced into the management of treatment-resistant depression (TRD). VNS has already received regulatory approval for TRD. This paper reviews the available clinical evidence and neurobiology of VNS and DBS in TRD. The principle of VNS is a stimulation of the left cervical vagus nerve with a programmable neurostimulator. VNS was examined in 4 clinical trials with 355 patients. VNS demonstrated steadily increasing improvement with full benefit after 6–12 months, sustained up to 2 years. Patients who responded best had a low-to-moderate antidepressant resistance. However, the primary results of the only controlled trial were negative. DBS involves stereotactical implantation of electrodes powered by a pulse generator into the specific brain regions. For depression, the targeted areas are the subthalamic nucleus, internal globus pallidus, ventral internal capsule/ventral striatum, the subgenual cingulated region, and the nucleus accumbens. Antidepressant effects of DBS were examined in case series with a total number of 50 TRD patients. Stimulation of different brain regions resulted in a reduction of depressive symptoms. The clinical data on the use of VNS and DBS in TRD are encouraging. The major contribution of the methods is a novel approach that allows for precise targeting of the specific brain areas, nuclei and circuits implicated in the etiopathogenesis of neuropsychiatric disorders. For clinical practice, it is necessary to identify patients who may best benefit from VNS or DBS.

Transcutaneous vagus and trigeminal nerve stimulation for neuropsychiatric disorders: a systematic review

“…Electric stimulation provides direct modulatory effects in subcortical sites, i.e, there are changes in cortical excitability. Neuroimaging studies corroborate these effects, showing neuronal activity changes in certain sites of brain, such as the amygdala, insula, precentral gyrus, hippocampus, and thalamus 4,5,16,21 . These neuroanatomical connections have been linked to the "bottom-up" mechanism of modulation by CNS 9 .…”

“…Different nonpharmacological brain stimulation techniques have been used in clinical neurology and psychiatry, such as electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), vagus nerve stimulation (VNS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), stereotactic surgery and trigeminal nerve stimulation (TNS) 1,2,3,4,5 . Theoretically, such techniques present different mechanisms of action.…”

Ablative Surgery for Neuropsychiatric Disorders: Past, Present, Future

“…The nerve delivers input to the forebrain via the parabrachial nucleus and locus ceruleus, which connect to central structures in the limbic system, such as the amygdala and hypothalamus [86]. Vagal nerve stimulation (VNS) has been explored with increasing reports of long-term success in the treatment for refractory depression [87]. Research has demonstrated VNS has a role in increasing serotonergic and noradrenergic activity in the brain with evidence that it increases perfusion of limbic structures [88,89].…”

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“…These methods are not adequately evaluated in the treatment of bipolar depression or for comparative effi cacy between unipolar and bipolar depression. They are reviewed elsewhere [ 124,128,167,168,191,207,225,242 ] .…”