&lt;p&gt;The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders&lt;/p&gt;

Sackeïm, Harold A.; Dibué, Maxine; Bunker, Mark; Rush, A. John

doi:10.2147/ndt.s286977

Cited by 8 publications

(5 citation statements)

References 89 publications

(123 reference statements)

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“…that were long thought to be under the sole control of the CNS (38,39). The evidence that perturbations in the gut precipitate serious mood disorders through the vagus nerve underscores the importance of this component of the GBA in the maintenance of normal behavior (40).…”

Section: Molecular Mechanisms Driving Ndsmentioning

confidence: 99%

Neurodegenerative disorders and gut-brain interactions

Singh¹,

Dawson²,

Kulkarni³

2021

Journal of Clinical Investigation

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Neurodegenerative disorders (NDs) are chronic and progressive disorders that disproportionately affect the elderly and have been characterized by selective loss of neurons in the CNS (1). Their prevalence is increasing -partly owing to extensions in lifespan -and by 2030, individuals affected by NDs will account for more than 8 million patients in the United States (2). Various NDs can be characterized and differentiated by their primary clinical features, the anatomical location of the neurodegeneration, the various cell types they affect, and/or the principal molecular abnormality that causes them (3).Prior to the considerable progress made in recent years that will be discussed here, psychiatrists, neurologists, and gastroenterologists alike supported the idea of the existence of a disease called the "institutional colon." This term described the presence of an amotile and/or elongated and largely distended colon with resulting gut dysfunctions in psychiatric patients who lived in mental health institutions (4). That such a disease existed was often questioned by contemporary physicians, and the confluence of gut and behavioral dysfunction was ascribed to the side effects of medicines, incorrect or inadequate diets, or inattention. To prove that the "institutional colon" is a true disease, Sonnenberg et al. (4) combed through millions of medical records at the US Veterans Affairs to show that patients with presenile dementia, Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), or Huntington's disease (HD) had significantly higher odds of also experiencing colonic dysfunction. The authors pointed out that "not all neurons involved in control of intestinal motility are located within the enteric nervous system, but may originate, for instance, in the vagal nuclei at the medulla oblongata or in the sacral segments of the spinal cord" and that "any referral to the loss of neuronal control of colonic motility does not allude to a common pathway, and leaves a multitude of heterogeneous mechanisms possible" (4). This landmark study showing the involvement of both gut and brain dysfunction in NDs paved the way for the studies discussed in this Review.Here, we review the processes associated with ND etiology and how various gut-innervating and gut-brain connecting neurons are either affected in NDs or are involved in their etiology. We also review the role of microbiota in driving NDs and discuss some open questions in this field. This Review will focus on the classical NDs -PD, AD, HD, and ALS -given that these are not only the major NDs but are also the diseases for which substantial information is available about associated gut dysfunctions.Neurodegenerative disorders (NDs) affect essential functions not only in the CNS, but also cause persistent gut dysfunctions, suggesting that they have an impact on both CNS and gut-innervating neurons. Although the CNS biology of NDs continues to be well studied, how gut-innervating neurons, including those that connect the gut to the brain, ...

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Section: Molecular Mechanisms Driving Ndsmentioning

confidence: 99%

Neurodegenerative disorders and gut-brain interactions

Singh¹,

Dawson²,

Kulkarni³

2021

Journal of Clinical Investigation

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“…In patients with high burdens of major depressive disorder (MDD), the available clinical evidence indicates a beneficial effect of adjunctive VNS Therapy with treatment-as-usual (TAU) in both response and long-term remission rates as well as an improvement in quality-of-life measures over time compared with TAU alone. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] The largest data set supporting the use of adjunctive VNS Therapy in the treatment of DTD demonstrated favorable outcomes in 494 participants who received adjunctive VNS Therapy plus TAU vs 301 patients with DTD who received only TAU. 25 The VNS + TAU group had a significantly higher five-year cumulative response rate (67.6% compared with 40.9%) and a significantly higher remission rate (cumulative first-time remitters, 43.3% compared with 25.7%).…”

Section: Introductionmentioning

confidence: 99%

Setting Up a Successful Vagus Nerve Stimulation Service for Patients With Difficult-to-Treat Depression

Kraus

Quach

Sholtes

et al. 2022

Neuromodulation: Technology at the Neural Interface

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Background: A substantial number of patients with major depressive disorder (MDD) do not sufficiently remit after the first lines of antidepressant treatments, making them vulnerable to poor clinical outcomes. Patients who have not had adequate resolution of their depressive symptoms after four antidepressant treatments and/or have been experiencing their current episode of MDD for two years or more (with insufficient responses to adequate antidepressant treatments) should be evaluated for antidepressant vagus nerve stimulation (VNS Therapy). Adjunctive VNS Therapy is a promising long-term treatment option for patients with difficult-to-treat depression (DTD), offering significantly improved remission rates in comparison with usual treatments. However, VNS Therapy requires specialized treatment centers to support patients. Materials and Methods:In this narrative review, we aim to outline the necessary steps for setting up an antidepressant VNS Therapy service in an efficient manner.Results: Establishing a VNS Therapy service requires several high-level considerations: initiation of a collaborative multidisciplinary team of health care professionals; developing a surgical pathway for implantation; consideration of reimbursement and health care coverage; setting up a specialist clinic to identify optimal candidates for VNS Therapy; educating patients and their families about VNS Therapy; and training health care providers on patient-specific VNS Therapy treatment and long-term treatment management.Conclusions: Antidepressant VNS Therapy is a promising treatment option for the long-term treatment of patients with DTD. We have successfully initiated four VNS Therapy service centers for DTD in the United States, Austria, and Germany. Based on our experiences and lessons learned, herein, we have provided advice to psychiatric centers planning to set up a VNS Therapy service for their patients with DTD.

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“…VNS has proven to be efficacious in patients with higher-order TRD (i.e., equal or greater than four prior antidepressants), and has also demonstrated durability of eff ect with maintenance treatment [234][235][236] . The FDA has approved VNS in TRD patients with a history of at least four prior failed antidepressants.…”

Section: Neurostimulationmentioning

confidence: 99%

Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions

McIntyre,

Alsuwaidan,

Baune

et al. 2023

World Psychiatry

124

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Treatment‐resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision‐making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision‐making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo‐resistant (e.g., due to inadequacy of treatment trials or non‐adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non‐response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co‐administered with an antidepressant) are established as efficacious in the management of TRD. Some second‐generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine‐fluoxetine combination has been studied in FDA‐defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA‐approved for individuals with TRD, with accelerated theta‐burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non‐inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual‐based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population.

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<p>The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders</p>

Cited by 8 publications

References 89 publications

Neurodegenerative disorders and gut-brain interactions

Neurodegenerative disorders and gut-brain interactions

Setting Up a Successful Vagus Nerve Stimulation Service for Patients With Difficult-to-Treat Depression

Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions

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