The purpose of this pilot study is to investigate the use of deep brain stimulation (DBS) of the substantia nigra pars reticulata (SNr) in subjects with treatment-resistant schizophrenia. There is a subset of patients with schizophrenia who continue to have persistent psychotic symptoms (auditory hallucinations and delusions) despite multiple adequate medication trials with antipsychotic medications including clozapine. There are currently no available treatments for such patients who generally have poor function and are chronically disabled, unable to work, live independently or have meaningful social relationships. Neuroimaging studies in patients with schizophrenia have revealed information about pathological neural circuits that could be suitable targets using deep brain stimulation. Although not yet tested in patients with schizophrenia, DBS is in early phase clinical trials in other psychiatric disorders. This pilot study will investigate the use of DBS in treatment-resistant schizophrenia subjects who have exhausted all other therapeutic alternatives but continue to have persistent disabling psychotic symptoms. Of note, DBS is not FDA approved for use in patients with schizophrenia. The method will be similar to that used in subthalamic nucleus stimulation in patients with Parkinson's Disease. However, the electrode will be advanced slightly inferior into the SNr, a major outflow nucleus of the basal ganglia, with the intention of causing local inhibition of SNr outflow resulting in disinhibition of the mediodorsal nucleus (MDN) of the thalamus. Hypofunction of the MDN has been implicated in the pathophysiology of schizophrenia in post-mortem as well as multiple structural and functional imaging studies. Evidence suggests that dysfunction of the MD is implicated in both positive and cognitive symptoms (such as working memory impairment) in schizophrenia. Frequent monitoring and clinical assessment with psychiatric scales will be used to monitor treatment response.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Placement of Deep brain stimulation System for treatment of chronic auditory hallucinations in treatment-resistant schizophrenia
The Johns Hopkins Hospital
Baltimore, Maryland, United States
RECRUITINGChange from baseline in the Brief Psychiatric Rating Scale
We will assess deep brain stimulation effects on the positive and psychosis features of schizophrenia.
Time frame: 1 year after neurostimulator implantation
Change from baseline in the Scales for the Assessment of Negative Symptoms (SANS)
We will assess deep brain stimulation effects on negative symptoms aspects of schizophrenia.
Time frame: 1 year after neurostimulator implantation
Incidence of adverse device effects (ADEs).
We will assess the incidence of adverse device effects as defined by the Code of Federal Regulations (21 CFR 812.3)
Time frame: 1 year after neurostimulator implantation
Change from baseline in the Young Mania scale (YMS)
We will assess deep brain stimulation effects on mania as assessed by the YMS.
Time frame: 1 year after neurostimulator implantation
Change from baseline in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) cognitive test battery.
We will assess deep brain stimulation effects on cognition as assessed by the MATRICS cognitive test battery.
Time frame: 1 year after neurostimulator implantation
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.