Transcranial Direct-current Stimulation (tDCS) in Treatment Refractory Auditory Hallucinations

The aim in this study is to conduct a pilot study on the efficacy of tDCS by assessing its
efficacy in treatment refractory auditory verbal hallucinations in inpatients with chronic
schizophrenia. Based on and expanding the findings by Brunelin et al. the hypothesis is that
tDCS treatment with the cathode on the left temporal-parietal junction and the anode on the
left dorsolateral prefrontal cortex can reduce the severity of auditory verbal hallucinations
in patients with treatment refractory schizophrenia. The impact of tDCS on other
schizophrenia symptoms in secondary exploratory outcome analyses together with the
examination of the durability of an ameliorating effect will also be investigated.

Inclusion Criteria:

- Inpatient adults (age 18-65 years) who meet diagnostic criteria for schizophrenia or
schizoaffective disorder (using the Structured Clinical Interview for DSM)

- Auditory hallucinations without remission over 5 years (remission is defined as a
period of 4 weeks without hallucinations) as documented in the patients' medical
record

- Failure to respond to two previous adequate antipsychotic trials with adequate
duration and adequate dosage

- Screening PANSS total rating of > 70

- PANSS hallucinatory behavior item > 4

- Capacity and willingness to sign informed consent

- On a stable antipsychotic regimen 4 weeks prior to screening and for the duration of
the trial

- Normal hearing

- If female and not infertile, must agree to use one of the following forms of
contraception for the duration of study participation: systemic hormonal treatment, an
interuterine device (IUD) which was implanted at least 2 months prior to screening, or
"double-barrier" contraception

- Willing to wear the tDCS device.

Exclusion Criteria:

- Prior history of seizure, other than that induced by Electro Convulsive Therapy

- Family history of seizures

- Significant unstable medical condition

- Pregnancy or women of childbearing capacity not using a medically accepted form of
contraception when engaged in sexual intercourse

- Inability to provide informed consent

- Actively suicidal and or showing violent behavior

- Significant organic brain pathology by history and neurological examination, inclusive
of history of head trauma, loss of consciousness for more than 5 minutes; intracranial
metal implants, known structural brain lesion, devices that may be affected by
transcranial Direct Current Stimulation (tDCS) (pacemaker, medication pump, cochlear
implant, implanted brain stimulator)

- Active substance abuse

- Increased intracranial pressure, unstable cardiovascular disease, sleep apnea

- Individuals with a clinically defined neurological disorder

- Frequent and persistent migraines

- History of adverse reaction to neurostimulation or open skin wounds that would
preclude safe placement of tDCS electrodes

- Current use of medications known to lower seizure threshold (serotonergic or tricyclic
antidepressants)

- If pregnant or breast feeding at the time of screening