Adjunct high-frequency transcranial random noise stimulation over the lateral prefrontal cortex improves negative symptoms of schizophrenia: A randomized, double-blind, sham-controlled pilot study

Chuan-Chia Chang; Yen-Yue Lin; Nian-Sheng Tzeng; Yu-Chen Kao; Hsin-An Chang

doi:10.1016/j.jpsychires.2020.10.008

Adjunct high-frequency transcranial random noise stimulation over the lateral prefrontal cortex improves negative symptoms of schizophrenia: A randomized, double-blind, sham-controlled pilot study

J Psychiatr Res. 2021 Jan:132:151-160. doi: 10.1016/j.jpsychires.2020.10.008. Epub 2020 Oct 16.

Authors

Chuan-Chia Chang¹, Yen-Yue Lin², Nian-Sheng Tzeng¹, Yu-Chen Kao³, Hsin-An Chang⁴

Affiliations

¹ Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
² Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Emergency Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan; Department of Life Sciences, National Central University, Taoyuan, Taiwan.
³ Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Psychiatry, Tri-Service General Hospital Songshan Branch, National Defense Medical Center, Taipei, Taiwan.
⁴ Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. Electronic address: chang.ha@mail.ndmctsgh.edu.tw.

PMID: 33096356
DOI: 10.1016/j.jpsychires.2020.10.008

Abstract

High-frequency transcranial random noise stimulation (hf-tRNS) is a non-invasive neuromodulatory technique capable of increasing human cortex excitability. There were only published case reports on the use of hf-tRNS targeting the lateral prefrontal cortex in treating negative symptoms of schizophrenia, thus necessitating systematic investigation. We designed a randomized, double-blind, sham-controlled trial in a cohort of stabilized schizophrenia patients to examine the efficacy of add-on hf-tRNS (100-640 Hz; 2 mA; 20 min) using a high definition 4 × 1 electrode montage (anode AF3, cathodes AF4, F2, F6, and FC4) in treating negative symptoms (ClinicalTrials.gov ID: NCT04038788). Participants received either active hf-tRNS or sham twice daily for 5 consecutive weekdays. Primary outcome measure was the change over time in the Positive and Negative Syndrome Scale Factor Score for Negative Symptoms (PANSS-FSNS), which was measured at baseline, after 10-session stimulation, and at one-week and one-month follow-ups. Among 36 randomized patients, 35 (97.2%) completed the trial. Intention-to-treat analysis showed a significantly greater decrease in PANSS-FSNS score after active (-17.11%) than after sham stimulation (-1.68%), with a large effect size (Cohen's d = 2.16, p < 0.001). The beneficial effect lasted for up to one month. In secondary-outcome analyses, the authors observed improvements with hf-tRNS of disorganization symptoms, unawareness of negative symptoms, subjective response to taking antipsychotics, and antipsychotic-induced extrapyramidal symptoms. No effects were observed on the neurocognitive performance and other outcome measures. Overall, hf-tRNS was safe and efficacious in improving negative symptoms. Our promising findings should be confirmed in a larger sample of patients with predominant negative symptoms.

Keywords: High definition montage; Negative symptoms; Prefrontal cortex; Schizophrenia; Transcranial random noise stimulation.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Double-Blind Method
Humans
Pilot Projects
Prefrontal Cortex
Schizophrenia* / therapy
Transcranial Direct Current Stimulation*
Transcranial Magnetic Stimulation
Treatment Outcome

Associated data

ClinicalTrials.gov/NCT04038788