Direct-Current Brain Stimulation Promising in Schizophrenia

Megan Brooks

May 18, 2012

May 18, 2012 — Transcranial direct-current stimulation (tDCS), a noninvasive treatment modality, may yield significant and lasting benefits in patients with schizophrenia who suffer from auditory verbal hallucinations that are unresponsive to antipsychotic medication, new research shows.

Investigators from the University of Lyon and Centre Hospitalier Le Vinatier in Bron, France, found that tDCS reduced auditory verbal hallucinations by an average of 31% in a small sham stimulation-controlled study, and the effect lasted for up to 3 months. tDCS also eased some other symptoms of schizophrenia.

First author Jerome Brunelin, PhD, told Medscape Medical News the current study suggests that with tDCS, "it's possible to alleviate a wide range of refractory symptoms in schizophrenia using noninvasive brain stimulation applied over a disturbed cerebral network."

He noted that tDCS is "cheaper and easier-use than TMS [transcranial magnetic stimulation] (and) the impact on symptomatology seems larger (impact on negative symptoms) and longer (at least 3 months duration) than that TMS currently permits. It is possible to imagine that tDCS could in the future be used at home by patients themselves."

The study was published online May 11 in the American Journal of Psychiatry.

The investigators note that about 25% to 30% of patients with schizophrenia have auditory verbal hallucinations that are refractory to medication, "resulting in persistent distress, functional disability, and frequent loss of behavioral control."

It has been shown that repetitive TMS (rTMS) can modulate cortical excitability to improve refractory auditory verbal hallucinations in schizophrenia. tDCS, the investigators note, is a fairly new noninvasive neurostimulation treatment that is increasingly being used for treatment of psychiatric and neurologic symptoms.

"With tDCS, the cortical neuronal excitability is increased in the vicinity of the anode (analogous to high-frequency rTMS) and is reduced near the cathode (analogous to low-frequency rTMS)," the authors write.

The study involved 30 patients with schizophrenia who experienced persistent daily auditory verbal hallucinations without remission despite 3 months of adequate-dose antipsychotic medication.

Study participants were randomly allocated to receive active tDCS or sham stimulation twice a day on 5 consecutive weekdays. The anode was placed over the left dorsolateral prefrontal cortex; the cathode was placed over the left temporo-parietal cortex. In accordance with recent studies of tDCS in other psychiatric and neurological illnesses, the stimulation level was set at 2 mA for 20 minutes.

The primary outcome was change in score on the Auditory Hallucination Rating Scale (AHRS). Assessments were made at baseline (before stimulation), after the 5 days of stimulation, and at 1 and 3 months after stimulation. Baseline AHRS scores were similar in the 2 groups, as were other variables, including age, sex, education, medication, and Positive and Negative Syndrome Scale (PANSS) scores.

Large Effect Size

Compared with sham stimulation, tDCS had a large effect on auditory verbal hallucinations after 5 days (Cohen's d = 1.58; P < .001), the investigators say. The active group had a mean reduction (improvement) in the AHRS score of 31% (from 28.3 to 19.9), compared with a reduction of only 8% (from 27.2 to 25.1) in the control group.

The beneficial effect of tDCS on hallucinations was still evident at the 1- and 3-month mark, with AHRS scores reduced in the tDCS group by 36% and 38%, respectively, compared with reductions of 3% and 5% at 1 and 3 months in the sham stimulation group.

Although a decrease in AHRS score was observed for all patients in the active treatment group, no patient had a complete resolution of their hallucinations (AHRS score of 0), the investigators note.

However, at the end of the trial, 40% of patients who underwent tDCS could still be categorized as responders (defined as a > 50% reduction in AHRS score), "which has not been the case with rTMS studies," the authors note. "This long-lasting effect could not be explained by changes in medications, as all patients maintained the same medication regimen throughout the study period."

As expected, the beneficial effect of active tDCS was not limited to auditory verbal hallucinations, the investigators say, with an improvement in PANSS total score after treatment, especially for the negative and positive dimensions; tDCS did not seem to have any effect on dimensions of disorganization or grandiosity/excitement.

"Further studies with larger samples and additional evaluations, such as functional evaluations (e.g., quality of life, social autonomy of patients) and imaging, are needed to confirm these promising results," the researchers say. On that front, Dr. Brunelin told Medscape Medical News, "a follow-up study is under way."

The study was supported by grant BIR MIRA 2008 from the Rhône-Alpes Region, France, and grant CSR 2007 from Le Vinatier Hospital. The authors have disclosed no relevant financial relationships.

Am J Psychiatry. Published online May 11, 2012. Abstract

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