Examining bi-anodal transcranial direct current stimulation (tDCS) over bilateral dorsolateral prefrontal cortex coupled with bilateral extracephalic references as a treatment for negative symptoms in non-acute schizophrenia patients: A randomized, double-blind, sham-controlled trial.

No studies have examined the efficacy of bi-anodal transcranial direct current stimulation (tDCS) over bilateral dorsolateral prefrontal cortex (DLPFC) coupled with bilateral extracephalic references in treating negative symptoms of non-acute schizophrenia patients. This study aimed to investigate the therapeutic effects of the new approach of tDCS on negative symptoms, other schizophrenia symptoms, cognitive deficits and psychosocial functioning in a double-blind, randomized, sham-controlled trial. Patients with non-acute schizophrenia (N = 60) in randomized order received sham treatment or bilaterally provided tDCS (2 mA, twice-daily sessions for five consecutive days) with the anode over the DLPFC and the reference (cathode) over the ipsilateral forearm. The negative symptoms as measured by a dimensional approach of Positive and Negative Syndrome Scale (PANSS) were rapidly reduced by bimodal tDCS relative to sham stimulation (F = 24.86, Cohen's d = 0.661, p = 6.11 × 10-6). The beneficial effect on negative symptoms lasted for up to 3 months. The authors also observed improvement with tDCS of psychosocial functioning as measured by the global score of Personal and Social Performance scale (PSP) and psychopathological symptoms especially for disorganization and cognitive symptoms as measured by the PANSS. No effects were observed on other schizophrenia symptom dimensions and the performance on a series of neurocognitive tests. Our results show promise for bi-anodal tDCS over bilateral DLPFC using bilateral extracephalic references in treating negative symptoms and other selected manifestations of schizophrenia. Further studies with electrophysiological or imaging evaluation help unravel the exact mechanism of action of this novel stimulation parameter of tDCS in schizophrenia patients. (ClinicalTrials.gov ID:NCT03701100).