Rapid effects of deep brain stimulation for treatment-resistant major depression

Treatment-resistant major depressive disorder is a prevalent and debilitating condition. Deep brain stimulation to different targets has been proposed as a putative treatment.

In this pilot study, we assessed safety and efficacy of deep brain stimulation to the supero-lateral branch of the medial forebrain bundle in seven patients with highly refractory depression. Primary outcome criterion was severity of treatment-resistant major depressive disorder as assessed with the Montgomery-Åsberg Depression Rating Scale. General psychopathologic parameters, social functioning, and tolerance were assessed with standardized scales, the Global Assessment of Functioning scale, quality of life (Short-Form Health Survey Questionnaire), and neuropsychological tests.

All patients showed strikingly similar intraoperative effects of increased appetitive motivation. Six patients attained the response criterion; response was rapid--mean Montgomery-Åsberg Depression Rating Scale of the whole sample was reduced by>50% at day 7 after onset of stimulation. At last observation (12-33 weeks), six patients were responders; among them, four were classified as remitters. Social functioning (Global Assessment of Functioning) improved in the sample as a whole from serious to mild impairment. Mean stimulation current was 2.86 mA; all side effects (strabismus at higher stimulation current, one small intracranial bleeding during surgery, infection at the implanted pulse generator site) could be resolved at short term.

These preliminary findings suggest that bilateral stimulation of the supero-lateral branch of the medial forebrain bundle may significantly reduce symptoms in treatment-resistant major depressive disorder. Onset of antidepressant efficacy was rapid (days), and a higher proportion of the population responded at lower stimulation intensities than observed in previous studies.