Non-invasive ear (auricular) vagus nerve stimulation for depression

Physiological and Molecular Mechanisms of Transcutaneous Auricular Vagus Nerve Stimulation in Depression

This study will test whether non-invasive ear (auricular) vagus nerve stimulation helps adults with major depressive or bipolar depressive episodes and which biological markers change with treatment.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 86 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Max-Planck-Institute of Psychiatry (other)
• Locations: 1 site (Munich)
• Trial ID: NCT07022171 on ClinicalTrials.gov

What this trial studies

AddVNS is a monocentric, randomized, double-blind, sham-controlled interventional study conducted at the Max Planck Institute of Psychiatry that plans to enroll 86 adult patients. Participants aged 18–65 with a current major depressive episode or bipolar depressive episode are randomized to either active transcutaneous auricular vagus nerve stimulation (tVNS) or sham stimulation for six weeks. The protocol combines clinical rating scales with biological sampling, neurophysiological measures, and biobanking to identify biomarkers and clarify mechanisms of action. The study also aims to explore optimal stimulation parameters and correlate physiological changes with clinical response.

Who should consider this trial

Good fit: Adults 18–65 years old with a current depressive episode (major depressive disorder or bipolar depression), able to give informed consent and willing to participate in biobanking, are the ideal candidates.

Not a fit: Patients who are pregnant or breastfeeding, have severe neurological disease, active substance abuse, anatomical contraindications to ear stimulation, are receiving other neurostimulation (ECT, rTMS, implanted VNS), or have severe general illness are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, tVNS could provide a non-invasive treatment option with fewer surgical risks and enable biomarker-guided personalization of therapy for people with depression.

How similar studies have performed: Previous smaller and largely non-randomized studies of tVNS have shown mixed signs of symptom improvement, but high-quality randomized evidence and agreement on optimal stimulation parameters remain limited.

Eligibility criteria

Inclusion Criteria:

1. age 18-65 years, legally competent and able to provide informed consent;
2. diagnosis of a depressive episode (MDD or bipolar disorder) according to DSM 4/DSM 5 or ICD-10/ICD-11;
3. signed informed consent documents for the AddVNS study;
4. signed informed consent and participation in the biobanking project of MPIP;
5. use of a safe contraceptive method

Exclusion Criteria:

1. age \< 18 years or age \> 65 years;
2. pregnancy or planning to get pregnant during the study period, breastfeeding;
3. legal supervision;
4. pervasive developmental disorders and/or intellectual disability;
5. acute substance abuse (e.g., alcohol, prescription or illicit drugs);
6. severe neurological disease;
7. technically or anatomically not possible tVNS (e.g., microtia or anotia, vagotomy);
8. current treatment with an established neurostimulation method (e.g., ECT, rTMS, VNS);
9. metallic foreign bodies, implanted intracranial devices or cerebral shunts;
10. severe general illness (e.g., relevant anemia requiring transfusion, high-grade cardiac arrythmia, severe cardiomyopathy);
11. active implants (e.g., cochlear implant, cardiac pacemaker, implantable cardioverter-defibrillator)

Where this trial is running

Munich

• Max Planck Institute of Psychiatry — Munich, Germany (RECRUITING)

Study contacts

• Principal investigator: Peter Falkai, MD — Max-Planck-Institute of Psychiatry
• Study coordinator: Evangelos Kokolakis, MD

Conditions: Depressive Disorder, Bipolar Disorder, transcutaneous, auricular, vagus nerve stimulation, biomarkers, depression