The Use of Transcranial Electrical Stimulation for Hallucinations

Purpose and Background

Schizophrenia is a serious mental health disorder with a constellation of positive, negative, and cognitive symptoms. Negative symptoms can include characteristics such as affective flattening, avolition, and alogia. Positive symptoms can include delusions, hallucinations, and disorganized speech or behavior. Auditory hallucinations (AH) are a hallmark of schizophrenia. They are reported in as many as 50-75% of patients with this diagnosis. The hallucinations experienced by patients vary greatly and can severely impact an individual's ability to function on a daily basis. In approximately 25-30% of patients diagnosed with schizophrenia, medication is an ineffective mechanism for managing these symptoms. These hallucinations are known as medication refractory auditory hallucinations (MRAH). They are defined as "the persistence of daily hallucinations without remission despite antipsychotic medication at an adequate dosage for at least three months".

For those whose AH do not respond to medication, non-surgical brain stimulation (NBS) has recently shown promise as a therapeutic intervention. Specifically, the use of conductive electrical approaches termed transcranial electrical stimulation (tES). One method of tES that has received renewed interest due to its high portability, safety, and modulatory effects is transcranial direct current stimulation (tDCS). tDCS involves applying a weak electrical current using saline soaked electrode sponges, causing either increases or decreases in cortical excitability, respectively. Research has shown in both healthy subjects and patients (e.g. Alzheimer's disease, Parkinson's disease, stroke, and depression) that tDCS has the potential to modulate synaptic and neurotransmitter-dependent plasticity underlying changes in behavior and learning. Brunelin et al utilized tDCS to successfully reduce MRAH in a population diagnosed with schizophrenia. They were able to reduce AH by approximately 30% in their sample after 5 days of twice-daily treatment and this effect was maintained for approximately three months following treatment. This finding has yet to be replicated in a similar study.

Along with tDCS, other new methods of NBS are being investigated across various disease states. One such study looked at the impact of tES on tinnitus. They tested whether type of tES made a difference in efficacy. They compared tDCS to tRNS. tRNS is very similar to tDCS except that it superimposes a random "white noise" gaussian waveform (from 0.1 hz to 640 hz) on top of the DC current. They found that tRNS induced a larger suppressive effect on tinnitus loudness and tinnitus-related distress when compared to tDCS. While their findings were in tinnitus, there are now multiple scholarly works describing a relationship of tinnitus and AH, possibly as a continuum or dimension underlying a variety of normal and disease states. This relationship suggests strategies found to be efficacious for tinnitus may in fact also be efficacious for AH. Recently, there was a case series showing possible efficacy in AH using tRNS.

The purpose of the study is to examine the efficacy of tES in the treatment of MRAH of schizophrenia. The hypothesis is that tRNS will provide a larger reduction of AH in those with schizophrenia as compared to tDCS and no treatment (i.e. sham). Confirmation of this hypothesis would provide an exciting new option for treatment and may provide an even higher level of efficacy than is seen in tDCS. Further, this study would also provide replication of the work by Brunelin et al. and further support of tES as a compelling tool for the management of severe MRAH.