Psychomodulation by bilateral deep brain stimulation of the lateral habenula in a patient with long-lasting, therapy-refractory major depression

Depression is a severe psychiatric illness with a sometimes therapy-refractory course. Deep brain stimulation (DBS) has been reported to be helpful in some of these cases. Stimulation of the ventral capsule/ventral striatum or the subcallosal cingulate is thought to normalize a chronic dysregulation of a well-described neurocircuitry in depression. We proposed that the same circuitry implicates an overactivation of the lateral habenula (LHb), which in turn could be downregulated via DBS resulting in an antidepressive action. We here report on the first patient with a severe therapy refractory major depressive disorder, who was bilaterally treated with DBS of the LHb. The female patient showed up with 4 severe relapses in the last 2.5 years while she was treated with maintenance electroconvulsive therapy (mECT) at a 7–10 days interval. After another complete ECT course she underwent neurosurgery in a short phase of full remission. With low stimulation parameters she relapsed within 5 weeks after surgery and -after turning to high stimulation parameters- she finally and fully remitted another 4 month later. Fluorodeoxyglucose positron emission tomography (FDG-PET) of the LHb showed a 10% decrease of glucose metabolism under high stimulation parameters. In conclusion, we report the first successful treatment of a severe treatment resistant depression with functional inhibition of the lateral habenula.