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

ABSTRACT: 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?

SUBMITTER: Valiengo LDCL

PROVIDER: S-EPMC6802484 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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

Valiengo Leandro da Costa Lane LDCL Goerigk Stephan S Gordon Pedro Caldana PC Padberg Frank F Serpa Mauricio Henriques MH Koebe Stephanie S Santos Leonardo Afonso Dos LAD Lovera Roger Alberto Marcos RAM Carvalho Juliana Barbosa de JB van de Bilt Martinus M Lacerda Acioly L T ALT Elkis Helio H Gattaz Wagner Farid WF Brunoni Andre R AR

JAMA psychiatry 20200201 2

<h4>Importance</h4>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.<h4>Objective</h4>To determine the efficacy and safety of tDCS vs sham as an add-on treatment for patients with schizophrenia and predominant negative symptoms.<h4>Design, setting, and participants</h4>The double-blind ...[more]

PMID: 31617873

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Project description:BackgroundsPatients with schizophrenia suffer from cognitive impairment that worsens real-world functional outcomes. We previously reported that multi-session transcranial direct current stimulation (tDCS) delivered to the left dorsolateral prefrontal cortex (DLPFC) improved daily living skills, while stimulation on the left superior temporal sulcus (STS) enhanced performance on a test of social cognition in these patients. To examine the region-dependent influence of tDCS on daily-living skills, neurocognition, and psychotic symptoms, this study compared effects of anodal stimulation targeting either of these two brain areas in patients with schizophrenia.MethodsData were collected from open-label, single-arm trials with anodal electrodes placed over the left DLPFC (N = 28) or STS (N = 15). Daily-living skills, neurocognition, and psychotic symptoms were measured with the UCSD performance-based skills assessment-brief (UPSA-B), Brief Assessment of Cognition in Schizophrenia (BACS), and Positive and Negative Syndrome Scale (PANSS), respectively. After baseline evaluation, tDCS (2 mA × 20 min) were delivered two times per day for 5 consecutive days. One month after the final stimulation, clinical assessments were repeated.ResultsPerformance on the UPSA-B was significantly improved in patients who received anodal tDCS at the left DLPFC (d = 0.70, p < 0.001), while this effect was absent in patients with anodal electrodes placed on the left STS (d = 0.02, p = 0.939). Significant improvement was also observed for scores on the BACS with anodal tDCS delivered to the DLPFC (d = 0.49, p < 0.001); however, such neurocognitive enhancement was absent when the STS was stimulated (d = 0.05, p = 0.646). Both methods of anodal stimulation showed a significant improvement of General Psychopathology scores on the PANSS (DLPFC, d = 0.50, p = 0.027; STS, d = 0.44, p = 0.001).ConclusionThese results indicate the importance of selecting brain regions as a target for tDCS according to clinical features of individual patients. Anodal stimulation of the left DLPFC may be advantageous in improving higher level functional outcomes in patients with schizophrenia.Trial registrationThese studies were registered within the University hospital Medical Information Network Clinical Trials Registry [(24), UMIN000015953], and the Japan Registry of Clinical Trials [(28), jRCTs032180026].

Project description:Patients with schizophrenia spectrum disorder often demonstrate impairments in action-outcome monitoring. Passivity phenomena and hallucinations, in particular, have been related to impairments of efference copy-based predictions which are relevant for the monitoring of outcomes produced by voluntary action. Frontal transcranial direct current stimulation has been shown to improve action-outcome monitoring in healthy subjects. However, whether transcranial direct current stimulation can improve action monitoring in patients with schizophrenia spectrum disorder remains unknown. We investigated whether transcranial direct current stimulation can improve the detection of temporal action-outcome discrepancies in patients with schizophrenia spectrum disorder. On 4 separate days, we applied sham or left cathodal/right anodal transcranial direct current stimulation in a randomized order to frontal (F3/F4), parietal (CP3/CP4) and frontoparietal (F3/CP4) areas of 19 patients with schizophrenia spectrum disorder and 26 healthy control subjects. Action-outcome monitoring was assessed subsequent to 10 min of sham/transcranial direct current stimulation (1.5 mA). After a self-generated (active) or externally generated (passive) key press, subjects were presented with a visual outcome (a dot on the screen), which was presented after various delays (0-417 ms). Participants had to detect delays between the key press and the visual consequence. Symptom subgroups were explored based on the presence or absence of symptoms related to a paranoid-hallucinatory syndrome. In general, delay-detection performance was impaired in the schizophrenia spectrum disorder compared to the healthy control group. Interaction analyses showed group-specific (schizophrenia spectrum disorder versus healthy control group) and symptom-specific (with/without relevant paranoid-hallucinatory symptoms) transcranial direct current stimulation effects. Post hoc tests revealed that frontal transcranial direct current stimulation improved the detection of long delays in active conditions and reduced the proportion of false alarms in undelayed trials of the passive condition in patients. The patients with no or few paranoid-hallucinatory symptoms benefited especially from frontal transcranial direct current stimulation in active conditions, while improvement in the patients with paranoid-hallucinatory symptoms was predominantly reflected in reduced false alarm rates in passive conditions. These data provide some first evidence for the potential utility of transcranial direct current stimulation in improving efference copy mechanisms and action-outcome monitoring in schizophrenia spectrum disorder. Current data indicate that improving efference copy-related processes can be especially effective in patients with no or few positive symptoms, while intersensory matching (i.e. task-relevant in passive conditions) could be more susceptible to improvement in patients with paranoid-hallucinatory symptoms.

Project description:BackgroundTranscranial Direct Current Stimulation (tDCS) and Transcranial Magnetic Stimulation (TMS) have been described as promising alternatives to treat different pain syndromes. This study evaluated the effects of TMS and tDCS in the treatment of chronic orofacial pain, through a systematic review.MethodsAn electronic search was performed in major databases: MEDLINE, Scopus, Web of Science, Cochrane, Embase, LILACS, BBO, Open Gray and CINAHL. The eligibility criteria comprised randomized clinical trials (RCTs) that applied TMS or tDCS to treat chronic orofacial pain. The variables analyzed were pain, functional limitation, quality of life, tolerance to treatment, somatosensory changes, and adverse effects. The risk of bias was assessed through the Cochrane Collaboration tool, and the certainty of evidence was evaluated through GRADE. The protocol was registered in the PROSPERO database (CRD42018090774).ResultsThe electronic search resulted in 636 studies. Thereafter, the eligibility criteria were applied and the duplicates removed, resulting in eight RCTs (four TMS and four tDCS). The findings of these studies suggest that rTMS applied to the Motor cortex (M1), the dorsolateral prefrontal cortex (DLPFC) and the secondary somatosensory cortex (S2) provide adequate orofacial pain relief. Two studies reported significant pain improvement with tDCS applied over M1 while the other two failed to demonstrate significant effects compared to placebo.ConclusionsrTMS, applied to M1, DLPFC or S2, is a promising approach for the treatment of chronic orofacial pain. Moreover, tDCS targeting M1 seems to be also effective in chronic orofacial pain treatment. The included studies used a wide variety of therapeutic protocols. In addition, most of them used small sample sizes, with a high risk of biases in their methodologies, thus producing a low quality of evidence. The results indicate that further research should be carried out with caution and with better-standardized therapeutic protocols.

Dataset Information

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

Publications

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

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