A Comprehensive Review of Vagus Nerve Stimulation for Depression

Austelle, Christopher W.; O’Leary, Georgia H.; Thompson, Sean; Gruber, Elise; Kahn, Alex T.; Manett, Andrew J.; Short, Baron; Badran, Bashar W.

doi:10.1111/ner.13528

Cited by 64 publications

(42 citation statements)

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“…Afferent information from the vagus nerve enters the nucleus tractus solitarius (NTS) and then spreads through the locus coeruleus (LC) to the various cortical regions, such as the sensorimotor cortex, anterior cingulate cortex (ACC), and insular cortex (Ins) [ 2 ]. Transcutaneous Vagus Nerve Stimulation (tVNS) enables noninvasive electrical stimulation of vagal afferents and has been reported to improve symptoms of seizures, depression, migraine headaches, COVID-19, cardiac disease, and stroke [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Neurophysiological changes underpinning the effects of tVNS reveal that stimulation either to the tragus or cymba conchae, the auricular branches of the vagus nerve, changes heart rate (HR) and heart rate variability (HRV) [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Stimulus Frequency, Intensity, and Sex on the Autonomic Response to Transcutaneous Vagus Nerve Stimulation

et al. 2022

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This study aimed to determine how transcutaneous vagus nerve stimulation (tVNS) alters autonomic nervous activity by comparing the effects of different tVNS frequencies and current intensities. We also investigated the sex-dependent autonomic response to tVNS. Thirty-five healthy adult participants were stimulated using a tVNS stimulator at the left cymba conchae while sitting on a reclining chair; tVNS-induced waveform changes were then recorded for different stimulus frequencies (Experiment 1: 3.0 mA at 100 Hz, 25 Hz, 10 Hz, 1 Hz, and 0 Hz (no stimulation)) and current intensities (Experiment 2: 100 Hz at 3.0 mA, 1.0 mA, 0.2 mA (below sensory threshold), and 0 mA (no stimulation)) using an electrocardiogram. Pulse widths were set at 250 µs in both experiment 1 and 2. Changes in heart rate (HR), root-mean-square of the difference between two successive R waves (RMSSD), and the ratio between low-frequency (LF) (0.04–0.15 Hz) and high-frequency (HF) (0.15–0.40 Hz) bands (LF/HF) in spectral analysis, which indicates sympathetic and parasympathetic activity, respectively, in heart rate variability (HRV), were recorded for analysis. Although stimulation at all frequencies significantly reduced HR (p = 0.001), stimulation at 100 Hz had the most pronounced effect (p = 0.001) in Experiment 1 and was revealed to be required to deliver at 3.0 mA in Experiment 2 (p = 0.003). Additionally, participants with higher baseline sympathetic activity experienced higher parasympathetic response during stimulation, and sex differences may exist in the autonomic responses by the application of tVNS. Therefore, our findings suggest that optimal autonomic changes induced by tVNS to the left cymba conchae vary depending on stimulating parameters and sex.

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Section: Introductionmentioning

confidence: 99%

Effects of Stimulus Frequency, Intensity, and Sex on the Autonomic Response to Transcutaneous Vagus Nerve Stimulation

et al. 2022

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“…It is well documented that VNS therapy may have a direct positive effect on behavior, concentration, and affect, often independent of seizure reduction ( 38 ). The recognized therapeutic effects of VNS in drug-resistant depression, as well as anxiety disorders and chronic headache, have also been suggested ( 39 – 41 ). Thus, the potential benefits of VNS on psychological and neurological disorders in refractory PTE patients could be further explored in the future.…”

Section: Discussionmentioning

confidence: 99%

Vagus nerve stimulation for refractory posttraumatic epilepsy: Efficacy and predictors of seizure outcome

et al. 2022

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BackgroundTraumatic brain injury (TBI) has been recognized as an important and common cause of epilepsy since antiquity. Posttraumatic epilepsy (PTE) is usually associated with drug resistance and poor surgical outcomes, thereby increasing the burden of the illness on patients and their families. Vagus nerve stimulation (VNS) is an adjunctive treatment for medically refractory epilepsy. This study aimed to determine the efficacy of VNS for refractory PTE and to initially evaluate the potential predictors of efficacy.MethodsWe retrospectively collected the outcomes of VNS with at least a 1-year follow-up in all patients with refractory PTE. Subgroups were classified as responders and non-responders according to the efficacy of VNS (≥50% or <50% reduction in seizure frequency). Preoperative data were analyzed to screen for potential predictors of VNS efficacy.ResultsIn total, forty-five patients with refractory PTE who underwent VNS therapy were enrolled. Responders were found in 64.4% of patients, and 15.6% of patients achieved seizure freedom at the last follow-up. In addition, the responder rate increased over time, with 37.8, 44.4, 60, and 67.6% at the 3-, 6-, 12-, and 24-month follow-ups, respectively. After multivariate analysis, generalized interictal epileptic discharges (IEDs) were found to be a negative predictor (OR: 4.861, 95% CI: 1.145–20.632) of VNS efficacy.ConclusionThe results indicated that VNS therapy was effective in refractory PTE patients and was well tolerated over a 1-year follow-up period. Patients with focal or multifocal IEDs were recognized to have better efficacy after VNS therapy.

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“…5 Direct stimulation of the ascending vagus nerve was approved by the US Food and Drug Administration (FDA) for medically intractable focal epilepsy in 1997 and later for depression. 6,7 Transcranial magnetic stimulation was approved for the treatment of major depression in 2008 and for treating pain with certain migraine headaches in 2013. 8 Advances in technology in the 2000s brought the first responsive neurostimulator for treating epilepsy, which uses embedded amplifiers and algorithms to sense and detect abnormal bioelectrical waveforms off implanted electrodes, and then apply targeted brain stimulation in response.…”

Section: Clinical Applicationsmentioning

confidence: 99%

Neuromodulation in 2035

Denison

Morrell

2022

Neurology

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Neuromodulation devices are approved in the United States for the treatment of movement disorders, epilepsy, pain, and depression, and are used off-label for other neurologic indications. By 2035, advances in our understanding of neuroanatomical networks and in the mechanism of action of stimulation, coupled with developments in material science, miniaturization, energy storage, and delivery, will expand the use of neuromodulation devices. Neuromodulation approaches are flexible and modifiable. Stimulation can be targeted to a dysfunctional brain focus, region, or network, and can be delivered as a single treatment, continuously, according to a duty cycle, or in response to physiologic changes. Programming can be titrated and modified based on the clinical response or a physiologic biomarker. In addition to keeping pace with clinical and technological developments, neurologists in 2035 will need to navigate complex ethical and economic considerations to ensure access to neuromodulation technology for a rapidly expanding population of patients. This article provides an overview of systems in use today and those that are anticipated and highlights the opportunities and challenges for the future, some of which are technical, but most of which will be addressed by learning about brain networks, and from rapidly growing experience with neuromodulation devices.

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A Comprehensive Review of Vagus Nerve Stimulation for Depression

Cited by 64 publications

References 50 publications

Effects of Stimulus Frequency, Intensity, and Sex on the Autonomic Response to Transcutaneous Vagus Nerve Stimulation

Effects of Stimulus Frequency, Intensity, and Sex on the Autonomic Response to Transcutaneous Vagus Nerve Stimulation

Vagus nerve stimulation for refractory posttraumatic epilepsy: Efficacy and predictors of seizure outcome

Neuromodulation in 2035

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