Highlights
- •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.
Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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.
ClinicalTrials.gov
NCT01898299.
Keywords
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Article info
Publication history
Published online: March 05, 2019
Accepted:
March 4,
2019
Received in revised form:
February 12,
2019
Received:
October 15,
2018
Identification
Copyright
© 2019 Elsevier Inc. All rights reserved.
