Significant improvement in treatment resistant auditory verbal hallucinations after 5 days of double-blind, randomized, sham controlled, fronto-temporal, transcranial direct current stimulation (tDCS): A replication/extension study

• Published in: Brain stimulation Vol. 12; no. 4; pp. 981 - 991
• Main Authors: Kantrowitz, Joshua T., Sehatpour, Pejman, Avissar, Michael, Horga, Guillermo, Gwak, Anna, Hoptman, Mathew J., Beggel, Odeta, Girgis, Ragy R., Vail, Blair, Silipo, Gail, Carlson, Marlene, Javitt, Daniel C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2019
• Subjects: Adult; Auditory hallucinations; Clinical trial; Double-Blind Method; Female; Frontal Lobe - diagnostic imaging; Frontal Lobe - physiology; Hallucinations - diagnostic imaging; Hallucinations - psychology; Hallucinations - therapy; Humans; Magnetic Resonance Imaging - methods; Male; Middle Aged; Schizophrenia; Schizophrenia - diagnosis; Schizophrenia - diagnostic imaging; Schizophrenia - therapy; Schizophrenic Psychology; Target engagement; tDCS; Temporal Lobe - diagnostic imaging; Temporal Lobe - physiology; Time Factors; Transcranial Direct Current Stimulation - methods; Treatment Outcome; Auditory hallucinations; Target engagement; Schizophrenia; Clinical trial; tDCS
• ISSN: 1935-861X; 1876-4754; 1876-4754
• DOI: 10.1016/j.brs.2019.03.003

Transcranial 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. 89 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. We 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. This 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. NCT01898299. •This is the largest study of tDCS for persistent AVH, with significant improvement seen in AVH through 1 month.•In post-hoc analyses, patients with lower cognitive symptoms showed greater improvement in AVH with tDCS.•In target engagement analysis, sufficient engagement was noted within the target language-sensitive regions.•We also saw off-target engagement that correlated with less robust clinical response.•Future studies using high-definition tDCS approaches may more precisely target auditory regions within the AVH network.