Cognitive effects of repeated sessions of transcranial direct current stimulation in patients with depression

The clinical utility of transcranial direct current stimulation (tDCS) has been discussed and explored for almost 40 years. In tDCS, a constant electric field is applied to the brain using two electrodes (anode and cathode) that results in a modulation of the cortical excitability and activity, and that depends on the stimulation polarity: Anodal stimulation increases cortical excitability and cathodal decreases it [Nitsche et al., 2003]. In psychiatry, tDCS studies of major depression and schizophrenia from the 1960s and 1970s showed mixed results [see review by Lolas, 1977]. The negative results of some of these trials can be attributed to the different methodology; in fact, recent investigations using different electrodes size and position, and different stimulation parameters have demonstrated that this technique is a robust method to modulate brain excitability probably on the basis of shifts in neuronal membrane excitability [Nitsche et al., 2003], and suggested that it might be helpful for stroke recovery [Hummel et al., 2005] and depression treatment [Fregni et al., 2006]. Much of this work is only preliminary and in need for further studies. However, the limited safety data available about tDCS restrict the design of larger clinical trials. In a recent study, Iyer et al. [2005] showed that a single session of tDCS (up to 2 mA) is safe in normal subjects. However, similar to repetitive transcranial magnetic stimulation treatment, long-lasting therapeutic effects of tDCS might be associated with repeated, rather than single, sessions of tDCS, and no cognitive safety data on this have been published to date. We report results from a preliminary double-blind, randomized, controlled study that evaluated the cognitive adverse effects of five sessions of tDCS of the left dorsolateral prefrontal cortex (DLPFC) in patients with major depression. In this trial, we investigated the cognitive effects of 5 days of anodal stimulation of the left DLPFC in 18 patients with major depression (46.479.4 years). Outpatients with unipolar major depression and without use of antidepressants for the last 3 months were recruited at the University of Sao Paulo (see demographic and clinical characteristics in Table 1). Patients with bipolar disorder or other psychiatric disorders were excluded. Recruited subjects were randomly assigned to one of two groups: active or sham tDCS. All patients were evaluated by the same rater, who remained blind to the results of the study group assignment. Because tDCS was applied over the DLPFC, we assessed cognitive performance through a battery of neuropsychological tests associated with prefrontal function. Furthermore, all adverse events were recorded. The neuropsychological battery, assessed immediately before the first day of treatment and immediately after the last treatment day (fifth session), consisted of the following tests: (1) MiniMental State Examination (MMSE) to measure global cognitive function; (2) Symbol Digits Modalities Test (SD) to measure processing speed; (3) Digit Span (subtest of the Wechsler Adult Intelligence Scale–III)— Forward (DSF) and Backward (DSB) to measure attention and working memory capacity; (4) Stroop (Victoria version): Colors (StC), Words (StW), and Interference Card (StIC) to measure complex focused and sustained attention; and (5) Five-Point Test (FP) to measure design fluency. We applied tDCS via a salinesoaked pair of surface sponge electrodes (35 cm).