This study tests if VNS Therapy helps people with tough-to-treat depression feel better. VNS stands for Vagus Nerve Stimulation. This therapy involves a device implanted in the body that sends mild pulses to the vagus nerve, which might help with depression. The study is split into two parts. In the first part, people are randomly chosen to get the VNS Therapy or not, and they are watched for 12 months. After 12 months, everyone will get the VNS Therapy. In the second part, up to 5,800 new participants will join and be followed for about 5 years. To join, you must have tried at least four other depression treatments that didn’t work and be on the same medication for at least four weeks before starting the study. You cannot join if you have certain mental health conditions like schizophrenia or bipolar disorder, or if you are currently having thoughts of self-harm.

• The study lasts for about 5 years.
• Participants are watched for 12 months before everyone gets the therapy.
• Initial participants are randomly selected for treatment or no treatment for the first 12 months.