"Mr. B" underwent unsuccessful treatment with long-term psychotherapy as well as multiple antidepressants before having a vagal nerve stimulator implanted and activated in March 2006. Prior to removal of the vagal nerve stimulator, he had experienced a 20% improvement in severe refractory depression. He felt that this improvement was clinically significant enough to allow him to be more functional than he had been in years, although he was still depressed. The vagal nerve stimulator was surgically removed in March 2008 after the patient developed meningitis, unrelated to the device, and required magnetic resonance imaging. Three weeks after explantation, the patient still felt stable. Within 2 months, he was acutely depressed and felt worse than prior to the stimulator implantation 3 years earlier, despite augmentation with venlafaxine extended release (450 mg), mirtazapine (30 mg), dextroamphetamine (70 mg), and quetiapine fumarate (100—300 mg) with L-methylfolate (7.5 mg). He considered disability status and could not function in his profession. He consulted a neurosurgeon but was cautioned against reimplantation because of anatomic damage sustained upon explantation. He then underwent failed treatment with three monoamine oxidase inhibitors before deriving significant, although incomplete, benefit without side effect from paroxetine (40 mg) with venlafaxine and dextroamphetamine. We had avoided this treatment combination initially in order to prevent serotonin syndrome, but since the patient had already received treatment with most other agents unsuccessfully, this was tried and used successfully, defined as improved work and family functioning without the need for disability status.