Query: Vagus nerve stimulation for psychotic disorders

title: Major Psychiatric Disorders Subsequent to Treating Epilepsy by Vagus Nerve Stimulation
abstract: The goal of this work was documentation of incidence, phenomenology, pathogenesis, and treatment of psychiatric disorders occurring subsequent to treating epilepsy by vagus nerve stimulation (VNS).Methods. In a series of 81 patients treated by VNS, all patients who developed major psychiatric complications underwent systematic psychiatric evaluation and treatment with psychotropic medication; VNS was modified if necessary. After the seizure frequency was reduced by at least 75% 7 of 81 patients (9% developed major psychiatric disorders: Six became severely dysphoric (5 with catastrophic rage and 4 with psychotic symptoms) and one became psychotic. All 7 patients had experienced dysphoric disorders and 2 had experienced psychotic episodes prior to the VNS treatment. Five patients had frequent daily seizures prior to treatment. Remission or satisfactory improvement was achieved with psychotropic medication in 6 patients, aided by decreasing or interrupting VNS in two patients. One patient was noncompliant and suffered a fatal outcome. Severe interictal dysphoric disorders associated with catastrophic rage and psychotic episodes may develop on suppressing seizures by VNS in patients with previous epilepsy related psychiatric disorders. Patients with multiple daily seizures may be more vulnerable to this occurrence. The phenomenon corresponds to the common finding of interictal dysphoric and psychotic symptoms emerging when inhibitory mechanisms predominate (alternative psychiatric disorders in the absence of seizures, or forced normalization of the EEG) The dysphoric symptom of catastrophic rage appears to occur more often on seizure suppression by VNS than by antiepileptic drugs. Psychiatric intervention, primarily with antidepressant medication, must be available to secure a good outcome; decrease of VNS may occasionally be required.

title: Putative Common Pathways in Therapeutic Brain Stimulation for Affective Disorders
abstract: Brain stimulation methods in the treatment of affective disorder are electroconvulsive therapy (ECT) transcranial magnetic stimulation (TMS) vagus nerve stimulation (VNS) and deep brain stimulation (DBS) Clinically, ECT is considered the strongest remedy in the treatment of severe depression, especially depression with psychotic features, and in the elderly. TMS, despite positive reports, is somewhat more controversial. VNS has, so far, only been used in treatment resistant depression with limited results. DBS may be of potential use in rare cases of treatment resistant cases of affective disorder. This article highlights the similarities and differences between the four stimulation methods. The main difference is the seizures necessary in ECT. A stronger involvement of the hippocampus following experimental seizures compared with effects in that region induced by TMS and VNS might explain the consistent findings of the superiority of ECT in the most severe cases of affective disorder.

title: [Psychiatric and Psychological Comorbidities in Epilepsy: Clinical Features and Psychiatric Management]
abstract: Psychiatric comorbidities, including mood, anxiety, psychotic disorders, and autism spectrum disorder are common in patients with epilepsy (PWE) often occurring at rates 2 3 fold or higher than in the general population without epilepsy. Furthermore, an attention should be paid to psychiatric symptoms together with those caused by antiepileptic drug therapy, epilepsy surgery, and vagus nerve stimulation because these therapies sometimes induce psychiatric comorbidities. It is important to differentiate psychogenic non epileptic seizures (PNES) from epilepsy, and to provide patients with psychiatric treatment. We focused on the process and certainty of diagnosis and the managements of PNES. An accurate, undistorted understanding of the relationship between mental status and epilepsy is essential to ensure appropriate therapy and avoid misconceptions and unnecessary treatment. Psychiatric and psychological states should be evaluated at the time of the first visit in every PWE and patients should be provided adequate psychiatric therapy if necessary within the overall therapeutic plan.

title: La estimulacion magnetica transcraneal para el tratamiento de alucinaciones auditivas refractarias en ninos y adolescentes
abstract: Transcranial magnetic stimulation (TMS) is a novel, non invasive neuromodulatory technique that utilices electromagnetic force to alter neuronal excitability. Hence, unlikely ECT (electroconvulsive therapy) anaesthesia is not required and the individual remains awake and clinically monitored; and in contrast with vagus nerve stimulation and deep brain stimulation, electrodes will not be placed in the brain. To date, it has been applied to a range of neuropsychiatric disorders and since 2008 it has been approved by FDA for the management of resistant depression without psychotic symptoms. Experience in schizophrenia and other psychosis is lesser and as always there are fewer studies in children and adolescentes, but as clinicians we know that the first onset of the most serious mental disorders occurs in childhood or adolescence and half of all lifetime disorders start by the mid teens. In so young patients is specially important finding more effective treatments and less harmful. TMS would represent an interesting therapeutic alternative since it can activate some regions while at the same time it can inhibit others: for example there are studies that explain improvent in negative symptoms through dorsolateral prefrontal cortex stimulation. Efficacy on auditory hallucinations by inhibition of left temporal cortex will be reviewed below.

title: [Vagus Nerve Stimulation for Affective Disorders]
abstract: Vagus nerve stimulation (VNS) is a minimally invasive neurostimulation method and was approved for drug resistant epilepsy in children and adults in Europe in 1994. The observation that depression the most common comorbidity in epilepsy improved with VNS prompted trials of VNS in treatment resistant depression (TRD) leading to European approval of VNS for TRD in 2001. Use of VNS for TRD patients in Germany is currently limited to a few highly specialized tertiary centers and the method is largely unknown in psychiatric clinical practice. We therefore systematically review the most recent publications on VNS in TRD as well as recommendations in guidelines and discuss the use of VNS in clinical practice. In the past 5 years, 5 level 2 studies and 4 level 3 studies were published on the effect of VNS in TRD patients. Clinical studies have failed to demonstrate short term efficacy of VNS in TRD patients. Long term efficacy of VNS in TRD patients is documented by multiple studies: the recently published largest ever investigation on the subject confirms favorable outcomes in TRD patients receiving adjunctive VNS in addition to treatment as usual compared to patients receiving treatment as usual only over a 5 year period. Long term efficacy of VNS is documented by level 2 evidence; however, it is not known which TRD patients have a higher probability of responding to VNS, which may complicate patient selection in clinical practice. Additionally, the unclear and variable definition of TRD may hinder or postpone adequate use of neurostimulation treatments.

title: Feasibility, safety and efficacy of transauricular vagus nerve stimulation in a cohort of patients with disorders of consciousness
abstract: Disorders of consciousness (DOC) are one of many neurological diseases for which there is still no curative treatment. The majority of therapeutic options performed in these patients have focused on accelerating clinical recovery through pharmacological interventions, environmental stimulation or, more recently, using neuromodulatory brain stimulation techniques, among others  Vagus nerve stimulation (VNS) has recently been used in neurorehabilitation based on its effects on cortical plasticity  Two recent case reports using VNS have shown promising results for increasing the level of consciousness in two patients in Vegetative State/Unresponsive Wakefulness Syndrome (VS/UWS) after severe traumatic brain injury [3,4] However the role of VNS in DOC has not been systematically studied. We prospectively enrolled chronic adult patients with DOC who weremore than six months post injury, and were receiving rehabilitation in our facility between May 2018 and January 2019. We included only patients with no changes in at least five Coma Recovery Scale Revised (CRS R) scores performed weekly in the four weeks before inclusion. The experimental intervention consisted of forty, 30 minute transauricular (left tragus) VNS (Parasym(r) CE) sessions administered twice a day (five days per week) Stimulation parameters (sinusoidal waveform; pulse width: 250 us; frequency: 20 Hz; amplitude: 1.5 mA) were chosen according to previous studies  All patients included in the study were assessed with the CRS R at baseline (T0) week 1 (T1) week 2 (T2) week 3 (T3) and week 4 (T4: end of treatment) with a further follow up 4 weeks after the termination of stimulation. Each subject's heart rate (HR) and blood pressure (BP) were monitored during all treatment sessions. Additionally, during the first VNS session, subjects were monitored by a multimodal monitor that included continuous ECG. Our primary outcome measure was the number of subjects presenting any improvement in at least one item in the CRS R evaluation at one time point. We also recorded the type and number of

title: The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult to Treat Mood Disorders
abstract: The Vagus Nerve Stimulation (VNS) Therapy System has been studied for more than 20 years in patients with severe, treatment resistant, chronic mood disorder, i.e. difficult to treat depression (DTD) This review distills some of the implications of this research for future therapeutic trials in this population.  A narrative review is provided on VNS in DTD. Protocols for a new, large, sham controlled trial and a global, longitudinal observational study are described.  Following encouraging results in open studies, a randomized, masked, sham controlled trial of VNS for DTD failed to demonstrate an effect on the primary outcome. The negative results may have been partly due to inadequate treatment duration (10 weeks) In long term observational studies, adjunctive VNS, combined with treatment as usual (VNS+TAU) was administered to more than 1100 DTD patients and compared with TAU alone in more than 400 patients. VNS+TAU had superior antidepressant effects, but maximal symptom reduction was often observed after 12 months or longer of stimulation. VNS+TAU had also marked superiority in durability of benefit. Sustained levels of symptom reduction below the traditional cutoff for response (i.e. 50% were associated with improved quality of life.  Most comparisons of VNS+TAU and TAU were derived from observational, open label studies.  The history of VNS in DTD has implications for interventional studies in this population, and perhaps other chronic medical disorders. The slow onset of benefit with VNS necessitates considerably longer controlled observation periods to establish efficacy. Durability of benefit should be routinely incorporated in efficacy assessment. New outcome metrics are needed to both categorically identify clinically meaningful benefit and to integrate information on symptom burden over time.

title: Trans auricular Vagus Nerve Stimulation in the Treatment of Recovered Patients Affected by Eating and Feeding Disorders and Their Comorbidities.
abstract: Eating and feeding disorders (EFD's) represent the psychiatric pathology with the highest mortality rate and one of the major disorders with the highest psychiatric and clinical comorbidity. The vagus nerve represents one of the main components of the sympathetic and parasympathetic nervous system and is involved in important neurophysiological functions. Previous studies have shown that vagal nerve stimulation is effective in the treatment of resistant major depression, epilepsy and anxiety disorders. In EFD's there are a spectrum of symptoms which with Transcutaneous auricular Vagus Nerve Stimulation (Ta VNS) therapy could have a therapeutic efficacy.  Sample subjects is composed by 15 female subjects aged 18 51. Admitted to a psychiatry community having diagnosed in according to DSM 5: anorexia nervosa (AN) (N=9) bulimia nervosa (BN) (N=5) binge eating disorder (BED) (N=1) Psychiatric comorbidities: bipolar disorder type 1 (N=4) bipolar disorder type 2 (N=6) border line disorder (N=5) The protocol included 9 weeks of Ta VNS stimulation at a frequency of 1.5 3.5 mA for 4 hours per day. The variables detected in four different times (t0, t1, t2, t3, t4) are the following: Heart Rate Variability (HRV) Hamilton Depression Rating Scale (HAMD HDRS 17) Body Mass Index (BMI) Beck Anxiety Index (BAI) RESULTS Data analysis showed statistically significant differences between recording times (p>0.05) in HAM D (t0=18.28+ 5.31; t4=9.14+ 7.15) in BAI (t0=24.7+ 10.99; t4=13.8+ 7.0) the reported values show how during (T0 T4) the treatment there are a decay of the degree in the depressive state, in the state of anxiety and an improvement in the value of BMI. In particular, the BMI in the AN BN sub sample had a minimum gain of 5% and a maximum of 11% The analysis of H.R.V. did not show a significant changes among subjects thus confirming the discordance of the activity of the sympathetic and parasympathetic nervous system in EFD's.  Although the sample does not possess a relevant value to determine long term efficacy of Ta VNS or on a larger number of patients, this study reports how the application of neuro stimulation in EFD's may become an ADD ON in therapeutic approach. Indeed, substantial improvements are highlighted in the results and confirmed hypotheses proposed by the study.

title: Assessment for vagus nerve stimulation in patients with difficult to treat depression: a model from the Newcastle Regional Affective Disorders Service (RADS)
abstract: Vagus nerve stimulation (VNS) has been shown to improve long term outcomes for some patients with difficult to treat depression (DTD) OBJECTIVES Set out criteria to support the identification of patients for whom VNS is a suitable treatment option.  Published clinical evidence, coupled with clinical experience garnered at the Regional Affective Disorders Service (RADS; Newcastle, UK) to inform VNS criteria.  Patients with major depressive disorder or bipolar disorder (predominantly depressive) and a history of failed trials of multiple treatment modalities including pharmacotherapy, psychotherapy and/or electroconvulsive therapy (ECT) may be suitable candidates for VNS, if no contraindications are present. In the RADS such patients are offered VNS if they are able to provide informed consent and two specialists agree it is appropriate.  VNS provides a valuable treatment option for DTD when used under appropriate circumstances; these assessment criteria facilitate the identification of patients with greatest potential to benefit.

title: The Transcutaneous Auricular Vagus Nerve Stimulation (TaVNS) in Treatment of Depression and Anxiety Disorders in Recovery Patient with Feeding and Eating Disorders
abstract: The present study examined on the transcutaneous auricular Vagus Nerve Stimulation (taVNS) in treatment of depression and anxiety disorders in recovery patient with Feeding and eating disorders. Severity of food addiction was related to increased depression, emotional eating, binge eating, anti fat attitudes, internalized weight bias, body shame, and low eating self efficacy, but not body satisfaction. The vagus nerve, historically cited as the pneumogastric nerve, is the tenth cranial nerve or CN X, and interfaces with the parasympathetic control of the heart, lungs, and digestive tract. Previous studies have demonstrated that vagal nerve is effective in the treatment of depression, epilepsy and anxiety disorders.