• Joshua T Kantrowitz, Pejman Sehatpour, Michael Avissar, Guillermo Horga, Anna Gwak, Mathew J Hoptman, Odeta Beggel, Ragy R Girgis, Blair Vail, Gail Silipo, Marlene Carlson, and Daniel C Javitt.
• Schizophrenia Research Center, Nathan Kline Institute, Orangeburg, NY, 10962, USA; Division of Experimental Therapeutics, Department of Psychiatry, Columbia University, USA; Division of Experimental Therapeutics, Department of Psychiatry, New York State Psychiatric Institute, New York, NY, 10032, USA. Electronic address: jk3380@cumc.columbia.edu.
• Brain Stimul. 2019 Jul 1; 12 (4): 981-991.

BackgroundTranscranial direct current stimulation (tDCS) is a potentially novel treatment for antipsychotic-resistant auditory verbal hallucinations (AVH) in schizophrenia. Nevertheless, results have been mixed across studies.Methods89 schizophrenia/schizoaffective subjects (active: 47; Sham: 42) were randomized to five days of twice-daily 20-min active tDCS vs. sham treatments across two recruitment sites. AVH severity was assessed using the Auditory Hallucination Rating Scale (AHRS) total score. To assess target engagement, MRI was obtained in a sub sample.ResultsWe observed a statistically significant, moderate effect-size change in AHRS total score across one-week and one-month favoring active treatment following covariation for baseline symptoms and antipsychotic dose (p = 0.036; d = 0.48). Greatest change was observed on the AHRS loudness item (p = 0.003; d = 0.69). In exploratory analyses, greatest effects on AHRS were observed in patients with lower cognitive symptoms (d = 0.61). In target engagement analysis, suprathreshold mean field-strength (>0.2 V/m) was seen within language-sensitive regions. However, off-target field-strength, which correlated significantly with less robust clinical response, was observed in anterior regions.ConclusionsThis is the largest study of tDCS for persistent AVH conducted to date. We replicate previous reports of significant therapeutic benefit, but only if medication dosage is considered, with patients receiving lowest medication dosage showing greatest effect. Response was also greatest in patients with lowest levels of cognitive symptoms. Overall, these findings support continued development of tDCS for persistent AVH, but also suggest that response may be influenced by specific patient and treatment characteristics. CLINICALTRIALS.GOV: NCT01898299.Copyright © 2019 Elsevier Inc. All rights reserved.

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