Condition · Evidence Hub
Vagus Nerve Stimulation for Depression
Does vagus nerve stimulation help with depression? 76 human studies have investigated VNS for depression, including 9 systematic reviews, 15 RCTs, and 17 controlled trials, published between 2000 and 2026, with 37 published since 2022. Studies use implanted (iVNS), transcutaneous auricular (taVNS), and transcutaneous cervical (tcVNS) stimulation. Findings vary by study design and population; the studies below are ranked by evidence strength so you can weigh the research directly.
9 systematic reviews · 15 RCTs · 17 controlled trials · 14 observational studies · 17 narrative reviews · 4 case reports
Evidence by Tier
strongest → weakest
- 9Systematic reviews & meta-analyses
- 15Randomised controlled trials
- 17Controlled clinical trials
- 14Observational & cohort studies
- 17Narrative & scoping reviews
- 4Case reports & series
Stimulation Method
- 38iVNS
- 36taVNS
- 2tcVNS
Research Momentum
37 of 76 studies (49%) published since 2022 — an actively growing evidence base.
The studies
76 studies · strongest evidence firstLong-term efficacy and safety of vagus nerve stimulation in treatment-resistant depression: A systematic review
Rosson et al. · Journal of Affective Disorders · 2026
systematic reviewsiVNSTranscutaneous Auricular Vagus Nerve Stimulation: Efficacy, Applications, and Challenges in Mood Disorders and Autonomic Regulation-A Narrative Review
Croft et al. · Military medicine · 2025
systematic reviewstaVNSThe efficacy and safety of transcutaneous auricular vagus nerve stimulation in the treatment of depressive disorder: a systematic review and meta-analysis of randomized controlled trials
Tan et al. · Journal of Affective Disorders · 2023
systematic reviewstaVNSAdjunctive Vagus Nerve Stimulation for Treatment-Resistant Depression: a Quantitative Analysis
Zhang et al. · The Psychiatric quarterly · 2020 · n = 1,048
systematic reviewsiVNSVagus Nerve Stimulation for Depression: A Systematic Review
Lv et al. · Frontiers in psychology · 2019 · n = 255
systematic reviewsiVNSVagus nerve stimulation (VNS) therapy in patients with treatment resistant depression: A systematic review and meta-analysis
Bottomley et al. · Comprehensive psychiatry · 2019
systematic reviewsiVNSA patient-level meta-analysis of studies evaluating vagus nerve stimulation therapy for treatment-resistant depression
Berry et al. · Medical devices (Auckland, N.Z.) · 2013 · n = 1,460
systematic reviewsiVNSSystematic review and meta-analysis of vagus nerve stimulation in the treatment of depression: variable results based on study designs
Martin & Martin-Sanchez · European psychiatry : the journal of the Association of European Psychiatrists · 2012
systematic reviewsiVNSSafety and efficacy of Vagus Nerve Stimulation in treatment-resistant depression. A systematic review
Daban et al. · Journal of affective disorders · 2008
systematic reviewsiVNSEffects of vagus nerve stimulation on daily function and quality of life in markedly treatment-resistant major depression: Findings from a one-year, randomized, sham-controlled trial
Rush et al. · Brain stimulation · 2025 · n = 493
RCTstaVNSEffect of transcutaneous vagus nerve stimulation in hemodialysis patients: A randomized controlled trial
Zhang et al. · Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy · 2025 · n = 63
RCTstaVNSVagus nerve stimulation in treatment-resistant depression: A one-year, randomized, sham-controlled trial
Conway et al. · Brain stimulation · 2025
RCTstaVNSMulti-species probiotic supplement enhances vagal nerve function - results of a randomized controlled trial in patients with depression and healthy controls
Mörkl et al. · Gut microbes · 2025
RCTstaVNSTranscutaneous Auricular Vagus Nerve Stimulation Treatment for Erythematotelangiectatic Rosacea: A Randomized Clinical Trial
Li et al. · JAMA dermatology · 2025
RCTstaVNSExtended-release ketamine tablets for treatment-resistant depression: a randomized placebo-controlled phase 2 trial
Glue et al. · Nature medicine · 2024 · n = 329
RCTstaVNSTranscutaneous auricular vagus nerve stimulation for post-stroke depression: a double-blind, randomized, placebo-controlled trial
Liu et al. · Journal of Affective Disorders · 2024 · n = 80
RCTstaVNSA pilot randomized controlled trial of supervised, at-home, self-administered transcutaneous auricular vagus nerve stimulation (taVNS) to manage long COVID symptoms
Badran et al. · Bioelectronic medicine · 2022
RCTstaVNSAn assessor-blinded, randomized comparative trial of transcutaneous auricular vagus nerve stimulation (taVNS) combined with cranial electroacupuncture vs. citalopram for depression with chronic pain
Li et al. · Frontiers in psychiatry · 2022
RCTstaVNSComparative Effectiveness of Transcutaneous Auricular Vagus Nerve Stimulation vs Citalopram for Major Depressive Disorder: A Randomized Trial
Li et al. · Neuromodulation : journal of the International Neuromodulation Society · 2022
RCTstaVNSTranscutaneous auricular vagus nerve stimulation influences gastric motility: A randomized, double-blind trial in healthy individuals
Steidel et al. · Brain stimulation · 2021
RCTstaVNSVagus Nerve Stimulation Therapy Randomized to Different Amounts of Electrical Charge for Treatment-Resistant Depression: Acute and Chronic Effects
Aaronson et al. · Brain stimulation · 2013 · n = 331
RCTsiVNSAuricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study
Hein et al. · Journal of Neural Transmission · 2013 · n = 37
RCTstaVNSBehavioural and cognitive effects during vagus nerve stimulation in children with intractable epilepsy - a randomized controlled trial
Klinkenberg et al. · European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society · 2013
RCTstaVNSVagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial
Rush et al. · Biological Psychiatry · 2005 · n = 235
RCTsiVNSAccelerated Transcutaneous Auricular Vagus Nerve Stimulation for Inpatient Depression and Anxiety: The iWAVE Open Label Pilot Trial
Austelle et al. · Neuromodulation : journal of the International Neuromodulation Society · 2025
controlled trialstaVNSTranscutaneous auricular vagus nerve stimulation modulating the brain topological architecture of functional network in major depressive disorder: an fMRI study
Guo et al. · Brain Sciences · 2024 · n = 19
controlled trialstaVNSVagus Nerve Stimulation Modulates Inflammation in Treatment-Resistant Depression Patients: A Pilot Study
Lespérance et al. · International journal of molecular sciences · 2024
controlled trialsiVNSEffect of transcutaneous auricular vagus nerve stimulation on major depressive disorder with peripartum onset: A multicenter, open-label, controlled proof-of-concept clinical trial (DELOS-1)
Deligiannidis et al. · Journal of affective disorders · 2022 · n = 25
controlled trialstaVNSAdjunctive vagus nerve stimulation for treatment-resistant depression: a preliminary study
Zhang et al. · International journal of psychiatry in clinical practice · 2022
controlled trialsiVNSTranscutaneous Vagal Nerve Stimulation in Treatment-Resistant Depression: A Feasibility Study
Evensen et al. · Neuromodulation : journal of the International Neuromodulation Society · 2022
controlled trialstaVNSModern neurosurgical techniques for psychiatric disorders
De Salles et al. · Progress in brain research · 2022
controlled trialsiVNSFeasibility study on transcutaneous auricular vagus nerve stimulation using millimeter waves
Song et al. · Biomedical physics & engineering express · 2021 · n = 7
controlled trialstaVNSVagus Nerve Stimulation As an Adjunctive Neurostimulation Tool in Treatment-resistant Depression
Moeller et al. · Journal of visualized experiments : JoVE · 2019
controlled trialsiVNSA distinct biomarker of continuous transcutaneous vagus nerve stimulation treatment in major depressive disorder
Tu et al. · Brain stimulation · 2018 · n = 41
controlled trialstaVNSEffect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: a nonrandomized controlled pilot study
Rong et al. · Journal of Affective Disorders · 2016 · n = 160
controlled trialstaVNSTranscutaneous vagus nerve stimulation modulates amygdala functional connectivity in patients with depression
Liu et al. · Journal of affective disorders · 2016 · n = 49
controlled trialstaVNSTranscutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder
Fang et al. · Biological Psychiatry · 2016 · n = 34
controlled trialstaVNSVagus Nerve Stimulation
Howland · Current behavioral neuroscience reports · 2014
controlled trialstcVNSChanges in hypothalamic-pituitary-adrenal axis measures after vagus nerve stimulation therapy in chronic depression
O'Keane et al. · Biological psychiatry · 2005
controlled trialsiVNSVagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome
Sackeim et al. · Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2001 · n = 60
controlled trialsiVNSVagus nerve stimulation (VNS) for treatment-resistant depressions: a multicenter study
Rush et al. · Biological psychiatry · 2000 · n = 30
controlled trialsiVNSDurability of the benefit of vagus nerve stimulation in markedly treatment-resistant major depression: a RECOVER trial report
Conway et al. · The international journal of neuropsychopharmacology · 2026 · n = 493
observational studiesiVNSPrognostic and Prescriptive Predictors of Treatment Response to Adjunctive VNS Therapy in Major Depressive Disorder: A RECOVER Trial Report
Aaronson et al. · The Journal of Clinical Psychiatry · 2025 · n = 493
observational studiesiVNSMapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study
He et al. · Brazilian Journal of Psychiatry · 2023 · n = 22
observational studiestaVNSNeural activity changes in first-episode, drug-naive patients with major depressive disorder after transcutaneous auricular vagus nerve stimulation treatment: A resting-state fMRI study
Yi et al. · Frontiers in neuroscience · 2022 · n = 20
observational studiestaVNSProlonged Longitudinal Transcutaneous Auricular Vagus Nerve Stimulation Effect on Striatal Functional Connectivity in Patients with Major Depressive Disorder
Zhang et al. · Brain sciences · 2022 · n = 15
observational studiestaVNSThe effects of vagus nerve stimulation on the course and outcomes of patients with bipolar disorder in a treatment-resistant depressive episode: a 5-year prospective registry
McAllister-Williams et al. · International journal of bipolar disorders · 2020 · n = 156
observational studiesiVNSA 5-year observational study of patients with treatment-resistant depression treated with vagus nerve stimulation or treatment as usual: comparison of response, remission, and suicidality
Aaronson et al. · American Journal of Psychiatry · 2017 · n = 795
observational studiesiVNSEfficacy and long-term tuning parameters of vagus nerve stimulation in long-term treated depressive patients
Muller et al. · Journal of Clinical Neuroscience · 2017 · n = 18
observational studiesiVNSTwo-year outcome of vagus nerve stimulation in treatment-resistant depression
Bajbouj et al. · Journal of clinical psychopharmacology · 2010 · n = 74
observational studiesiVNSVagus nerve stimulation for depression: efficacy and safety in a European study
Schlaepfer et al. · Psychological medicine · 2008 · n = 74
observational studiesiVNSA one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression
George et al. · Biological psychiatry · 2005 · n = 329
observational studiesiVNSEffects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study
Rush et al. · Biological psychiatry · 2005 · n = 205
observational studiesiVNSTwo-year outcome of vagus nerve stimulation (VNS) for treatment of major depressive episodes
Nahas et al. · The Journal of clinical psychiatry · 2005 · n = 59
observational studiesiVNSVagus nerve stimulation (VNS) for major depressive episodes: one year outcomes
Marangell et al. · Biological psychiatry · 2002 · n = 30
observational studiesiVNSClinical application of transcutaneous auricular vagus nerve stimulation: a scoping review
Gerges et al. · Disability and rehabilitation · 2024 · n = 214
narrative reviewstaVNSTranscutaneous Auricular Vagus Nerve Stimulation to Improve Emotional State
Aranberri Ruiz · Biomedicines · 2024
narrative reviewstaVNSVagus nerve stimulation (VNS): recent advances and future directions
Austelle et al. · Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2024
narrative reviewstcVNSVagus Nerve Stimulation in Treatment-Resistant Depression: A Case Series of Long-Term Follow-up
Pigato et al. · The journal of ECT · 2023 · n = 5
case reportsiVNSTreatment-Resistant Late-Life Depression: A Review of Clinical Features, Neuropsychology, Neurobiology, and Treatment
Subramanian et al. · The Psychiatric clinics of North America · 2023
narrative reviewsiVNSNovel and emerging treatments for major depression
Marwaha et al. · Lancet (London, England) · 2023
narrative reviewsiVNSTranscutaneous vagus nerve stimulation - A brief introduction and overview
Hilz · Autonomic neuroscience : basic & clinical · 2022
narrative reviewstaVNSA Comprehensive Review of Vagus Nerve Stimulation for Depression
Austelle et al. · Neuromodulation : journal of the International Neuromodulation Society · 2022
narrative reviewstaVNSTranscutaneous auricular vagus nerve stimulators: a review of past, present, and future devices
Wang et al. · Expert review of medical devices · 2022
narrative reviewstaVNSTreatment-resistant bipolar depression: concepts and challenges for novel interventions
Diaz et al. · Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) · 2022
narrative reviewsiVNSVagus nerve stimulation: An update on a novel treatment for treatment-resistant depression
Kamel et al. · Journal of the neurological sciences · 2022
narrative reviewsiVNSVagus nerve stimulation for conservative therapy-refractive epilepsy and depression
Möbius et al. · Laryngo- rhino- otologie · 2022
narrative reviewstaVNSUse of transcutaneous auricular vagus nerve stimulation in the treatment of drug-resistant depression - a pilot study, presentation of five clinical cases
Kaczmarczyk et al. · Psychiatria polska · 2021 · n = 5
case reportstaVNSNeural networks and the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation in depression
Liu et al. · Journal of neuroinflammation · 2020
narrative reviewstaVNSVagus nerve stimulation for treatment-resistant depression: is this therapy distinct from other antidepressant treatments?
Vlaicu et al. · International journal of psychiatry in clinical practice · 2020
narrative reviewsiVNSTreating Depression with Transcutaneous Auricular Vagus Nerve Stimulation: State of the Art and Future Perspectives
Kong et al. · Frontiers in Psychiatry · 2018
narrative reviewstaVNSThe Mechanism of Action of Vagus Nerve Stimulation in Treatment-Resistant Depression: Current Conceptualizations
Conway et al. · The Psychiatric clinics of North America · 2018
narrative reviewsiVNSVagus nerve stimulation therapy in treatment-resistant depression: A series report
Tisi et al. · Psychiatry and clinical neurosciences · 2014 · n = 27
case reportsiVNSVagus nerve stimulation for chronic major depressive disorder: 12-month outcomes in highly treatment-refractory patients
Christmas et al. · Journal of affective disorders · 2013 · n = 41
case reportsiVNSClinical issues in considering vagus nerve stimulation for treatment-resistant depression
Rush et al. · Experimental neurology · 2009
narrative reviewsiVNSVagus nerve stimulation for severe depression
Rado et al. · Journal of psychosocial nursing and mental health services · 2007
narrative reviewsiVNS
Registered trials — results pending
8 registered protocols with no published results yet. Listed for context; not counted in the evidence total.
Protocol of the randomized double blind sham controlled AddVNS study of transcutaneous vagus nerve stimulation mechanisms in depression
Kokolakis et al. · 2026 · protocol
Effect of transcutaneous vagus nerve stimulation with electrical stimulation on generalized anxiety disorder: Study protocol for an assessor-participant blinded, randomized sham-controlled trial
Lai et al. · 2025 · protocol
Efficacy of auricular point-vagus nerve stimulation in adolescent insomnia patients and the brain function regulation mechanisms: a study protocol for an experimental, randomized, controlled clinical trial
He et al. · 2025 · protocol
Investigating the Microbiota-Gut-Brain Axis Mechanisms of Transcutaneous Auricular Vagus Nerve Stimulation in Patients with Obesity: A Study Protocol for a Randomized Controlled Trial
Chen et al. · 2025 · protocol
Transcutaneous auricular vagus nerve stimulation to acutely reduce emotional vulnerability and improve emotional regulation in borderline personality disorder (tVNS-BPD): study protocol for a randomized, single-blind, sham-controlled trial
Guerriero et al. · 2024 · protocol
Deep brain stimulation versus vagus nerve stimulation for the motor function of poststroke hemiplegia: study protocol for a multicentre randomised controlled trial
Xu et al. · 2024 · protocol
A prospective, multi-center randomized, controlled, blinded trial of vagus nerve stimulation for difficult to treat depression: A novel design for a novel treatment
Conway et al. · 2020 · protocol
Efficacy and brain mechanism of transcutaneous auricular vagus nerve stimulation for adolescents with mild to moderate depression: Study protocol for a randomized controlled trial
Xiao et al. · 2020 · protocol