Symposium
Session Room: M1
Session Room: M1
Saturday, June 27, 10:50 AM – 12:05 PM
Symposium 3:
Vagus nerve stimulation (VNS) for difficult-to-treat depression: Evidence for effectiveness, mechanisms of action, and its role in patient management
Vagus nerve stimulation (VNS) for difficult-to-treat depression: Evidence for effectiveness, mechanisms of action, and its role in patient management
Difficult-to- treat depression (DTD), particularly after non-responded to multiple treatments, is characterised by persistent depressive symptoms, impaired psychosocial function and quality of life (QoL)1, and high risk of relapse2. One treatment that may address this unmet need is vagus nerve stimulation (VNS). Previous long-term open-label follow-up over 5 years suggests that in patients with DTD, VNS plus treatment as usual (TAU) is associated with higher response and remission rates3, greater improvement in QoL4 and lower risk of relapse5 compared with those who just received TAU.
This symposium, chaired by Maria Strauß, University of Leipzig Medical Center, will present new data regarding the effectiveness of VNS in patients with markedly DTD, potential mechanisms of action and clinical role of VNS.
Impact of VNS on depressive symptoms, function and quality of life in patients with markedly treatment resistant difficult-to-treat depression: Findings from the US RECOVER study – A. John Rush (Duke–NUS Medical School, Singapore).
The RECOVER study is a one-year double-blind, randomised controlled trial of VNS in 500 patients with DTD, conducted in the USA. On average, current episode duration was 18 years, patients were in the 97th percentile for disability severity and had a mean of 13 failed antidepressants in their lifetimes1. 46% had a history of electroconvulsive treatment. Novel data from the study will be presented showing impact of VNS on depressive symptomatology6, improvements in function and QoL7 and the long-term durability of effects. Despite the significant baseline illness severity around 2/3 of patients achieved minimally clinically important improvement in symptoms, function and/or QoL with VNS8, underscoring the broad long-term effects of VNS.
Potential mechanisms of action of VNS in DTD – Bernhard Baune (University of Münster, Germany)
Replicated findings of multiple effects of VNS have been observed in animal models and patient populations. Cervical VNS activates predominantly afferent vagal fibers (~80%) which induces, via the nucleus tractus solitarius (NTS), locus coeruleus and dorsal raphe. This, in turn, increases forebrain norepinephrine and serotonin tone9 with a secondary modulation of dopaminergic tone10. VNS also exerts effects on the cortico-limbic network modulation via NTS projections (parabrachial, thalamic, hypothalamic relays) and alters activity and connectivity in mood circuits—amygdala, hippocampus, insula, prefrontal/orbitofrontal cortex, anterior cingulate (incl. sgACC)11. Additionally, VNS is associated with a reduction in inflammatory cytokines12, stress-system (HPA axis) normalization13, autonomic rebalance14, and stimulation of synaptic plasticity and trophic effects15.
Role of VNS in the clinical management of DTD and implications for future research – R. Hamish McAllister-Williams (Newcastle University, UK)
Data demonstrating efficacy of VNS in a naturalistic European Cohort (Restore-Life) will be presented16. The implications of this plus the RECOVER study findings to the management of DTD will be discussed, with reference to a published generic model of care of DTD17, RECOVER data18 and results from a Delphi process examining views of clinical experts in the field. It will conclude by considering how studies in patients with markedly DTD are conducted, specifically regarding the nature of the primary outcome and time period over which this is assessed19,20
This symposium, chaired by Maria Strauß, University of Leipzig Medical Center, will present new data regarding the effectiveness of VNS in patients with markedly DTD, potential mechanisms of action and clinical role of VNS.
Impact of VNS on depressive symptoms, function and quality of life in patients with markedly treatment resistant difficult-to-treat depression: Findings from the US RECOVER study – A. John Rush (Duke–NUS Medical School, Singapore).
The RECOVER study is a one-year double-blind, randomised controlled trial of VNS in 500 patients with DTD, conducted in the USA. On average, current episode duration was 18 years, patients were in the 97th percentile for disability severity and had a mean of 13 failed antidepressants in their lifetimes1. 46% had a history of electroconvulsive treatment. Novel data from the study will be presented showing impact of VNS on depressive symptomatology6, improvements in function and QoL7 and the long-term durability of effects. Despite the significant baseline illness severity around 2/3 of patients achieved minimally clinically important improvement in symptoms, function and/or QoL with VNS8, underscoring the broad long-term effects of VNS.
Potential mechanisms of action of VNS in DTD – Bernhard Baune (University of Münster, Germany)
Replicated findings of multiple effects of VNS have been observed in animal models and patient populations. Cervical VNS activates predominantly afferent vagal fibers (~80%) which induces, via the nucleus tractus solitarius (NTS), locus coeruleus and dorsal raphe. This, in turn, increases forebrain norepinephrine and serotonin tone9 with a secondary modulation of dopaminergic tone10. VNS also exerts effects on the cortico-limbic network modulation via NTS projections (parabrachial, thalamic, hypothalamic relays) and alters activity and connectivity in mood circuits—amygdala, hippocampus, insula, prefrontal/orbitofrontal cortex, anterior cingulate (incl. sgACC)11. Additionally, VNS is associated with a reduction in inflammatory cytokines12, stress-system (HPA axis) normalization13, autonomic rebalance14, and stimulation of synaptic plasticity and trophic effects15.
Role of VNS in the clinical management of DTD and implications for future research – R. Hamish McAllister-Williams (Newcastle University, UK)
Data demonstrating efficacy of VNS in a naturalistic European Cohort (Restore-Life) will be presented16. The implications of this plus the RECOVER study findings to the management of DTD will be discussed, with reference to a published generic model of care of DTD17, RECOVER data18 and results from a Delphi process examining views of clinical experts in the field. It will conclude by considering how studies in patients with markedly DTD are conducted, specifically regarding the nature of the primary outcome and time period over which this is assessed19,20
11:15 AM – 11:40 AM
25 min
25 min