Deep brain stimulation for management of treatment-refractory schizophrenia: A translational review for clinical integration

Background and hypothesis: With a typical clinical onset in late adolescence and early adulthood, schizophrenia is a severe illness and one of the top ten global causes of disability. Despite improvements in the pharmacological treatment available, 30 % of patients have chronic symptoms and disability, the unemployment rate is at 80–90 %, and patients' life expectancy is reduced by 10–20 years. Deep brain stimulation (DBS) has proven to be effective for different neuropsychiatric diseases, and there is an increased commitment to advanced invasive neuromodulation options for this severe disease. Study design: We performed a translational review of the efficacy and adverse effect profile of DBS in patients with schizophrenia using medical subject headings related to DBS and schizophrenia in MEDLINE (OVID interface), Web of Science, and Cochrane Central Register of Controlled Trials. There were no restrictions on study design, outcome, or language. We then performed a narrative review of the neuroscientific understanding of brain networks involved in schizophrenia, and how this may inform target location and explain outcomes observed in the reviewed studies. Study results: Following the PRISMA guidelines, 6 studies involving 11 patients who received DBS in the substantia nigra pars reticulata, subgenual anterior cingulate cortex, nucleus accumbens, and habenula were included in the review. None of the studies were sham-controlled and all were open-label. Overall, progressive improvements in the negative symptoms and auditory hallucinations have been reported. Despite an initial improvement, one patient worsened, and two patients presented complications related to the surgery. Conclusion: This systematic review presents emerging data regarding the possible utility of DBS in patients with refractory schizophrenia. Nonetheless, the available data have a high risk of bias, and multicenter trials are required to further refine the ability of DBS to target neural networks affected by schizophrenia.