[Skip to Content]
[Skip to Content Landing]
Original Investigation
October 16, 2019

Efficacy and Safety of Transcranial Direct Current Stimulation for Treating Negative Symptoms in Schizophrenia: A Randomized Clinical Trial

Author Affiliations
  • 1Laboratory of Neurosciences (LIM-27), Department and Institute of Psychiatry, Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBioN), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
  • 2Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
  • 3Department of Psychological Methodology and Assessment, Ludwig Maximilian University of Munich, Munich, Germany
  • 4Hochschule Fresenius, University of Applied Sciences, Munich, Germany
  • 5Department of Neurology and Stroke, Hertie Institute for Clinical Brain Research, Eberhard Karls University of Tübingen, Tübingen, Germany
  • 6Laboratory of Neuroimaging (LIM-21), Department and Institute of Psychiatry, Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBioN), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
  • 7Instituto Bairral de Psiquiatria, Itapira, Brazil
  • 8Programa de Transtornos Afetivos, Laboratório Interdisciplinar de Neurociências Clínicas, Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil
  • 9Department and Institute of Psychiatry, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
  • 10Department of Internal Medicine, Faculdade de Medicina da Universidade de São Paulo and Hospital Universitário, Universidade de São Paulo, São Paulo, Brazil
JAMA Psychiatry. 2020;77(2):121-129. doi:10.1001/jamapsychiatry.2019.3199
Key Points

Question  Is transcranial direct current stimulation (tDCS) a safe and effective add-on therapy for negative symptoms in schizophrenia?

Findings  In this randomized clinical trial of 100 patients with schizophrenia with predominant negative symptoms, active tDCS was superior to sham in ameliorating negative symptoms, with superior response rates (20% improvement) for negative symptoms. These effects were sustained at follow-up, and tDCS was not associated with significant adverse effects.

Meaning  Transcranial direct current stimulation is an affordable, safe, and effective add-on treatment for negative symptoms in schizophrenia.


Importance  Negative symptoms represent a substantial burden in schizophrenia. Although preliminary studies have suggested that transcranial direct current stimulation (tDCS) is effective for some clusters of symptoms, the clinical benefits for negative symptoms are unclear.

Objective  To determine the efficacy and safety of tDCS vs sham as an add-on treatment for patients with schizophrenia and predominant negative symptoms.

Design, Setting, and Participants  The double-blind Schizophrenia Treatment With Electric Transcranial Stimulation (STARTS) randomized clinical trial was conducted from September 2014 to March 2018 in 2 outpatient clinics in the state of São Paulo, Brazil. Patients with schizophrenia with stable negative and positive symptoms and a minimum score of 20 points in the negative symptoms subscale of the Positive and Negative Syndrome Scale (PANSS) were included.

Interventions  Ten sessions of tDCS performed twice a day for 5 days or a sham procedure. The anode and the cathode were positioned over the left prefrontal cortex and the left temporoparietal junction, respectively.

Main Outcomes and Measures  Change in the PANSS negative symptoms subscale score at week 6 was the primary outcome. Patients were followed-up for an additional 6 weeks.

Results  Of the 100 included patients, 20 (20.0%) were female, and the mean (SD) age was 35.3 (9.3) years. A total of 95 patients (95.0%) finished the trial. In the intention-to-treat analysis, patients receiving active tDCS showed a significantly greater improvement in PANSS score compared with those receiving the sham procedure (difference, 2.65; 95% CI, 1.51-3.79; number needed to treat, 3.18; 95% CI, 2.12-6.99; P < .001). Response rates for negative symptoms (20% improvement or greater) were also higher in the active group (20 of 50 [40%]) vs the sham group (2 of 50 [4%]) (P < .001). These effects persisted at follow-up. Transcranial direct current stimulation was well tolerated, and adverse effects did not differ between groups, except for burning sensation over the scalp in the active group (43.8%) vs the sham group (14.3%) (P = .003).

Conclusions and Relevance  Transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia.

Trial Registration  ClinicalTrials.gov identifier: NCT02535676

Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words