Subject: Depression

Short Description: Transcranial Direct Current Stimulation for Depression

Background: 
Nonpharmacological methods to treat depression include more than just ECT: recent developments include promising strategies like repetitive transcranial magnetic stimulation (rTMS) and vagal nerve stimulation (VNS). Another procedure, transcranial direct current stimulation (tDCS) involves the application of weak direct electrical current to the brain via scalp electrodes, which can be positioned to deliver currents that increase or decrease cortical excitability. It is relatively painless and involves no anesthesia.

A recent study evaluated the effect of tDCS with and without sertraline in 120 patients with moderate to severe depression (defined as Hamilton depression rating scale score >17). In a 2x2 design, half of these patients received tDCS while the other half received “sham” tDCS. Half also received sertraline (Zoloft) 50 mg/day, while the other half received placebo. Thus, there were four treatment groups: tDCS+sertraline, tDCS+placebo, sham+sertraline, and sham+placebo.

The tDCS protocol consisted of 20- to 30-minute daily sessions (Monday–Friday) for two weeks, plus two extra sessions in weeks 4 and 6. Electrodes were positioned to enhance activity in the left dorsolateral prefrontal cortex (DLPFC) and reduce right DLPFC activity.

At the end of six weeks, patients receiving combined tDCS+sertraline fared best, with a mean decrease in 11.5 points relative to sham+placebo, on the Montgomery-Åsberg Depression Rating Scale (MADRS) (p<.001). Combined treatment was also better than sham+sertraline (by 8.5 points, p=.002) and tDCS+placebo (by 5.9 points, p=.03). tDCS was statistically different from sham tDCS (mean difference of 5.6 points, p=.01), but sertraline was not statistically different from placebo (only 2.9 points, p=.20).

Response rates (>50% reduction in MADRS) were 16.7% for sham+placebo, 33.3% for sham+sertraline, 43.3% for tDCS+placebo, and 63.3% for tDCS+sertraline. Remission (MADRS?10) was observed in 40% of tDCS+placebo and 46.7% of those receiving combined treatment, but only 30% of those receiving sham+sertraline. MADRS scores were statistically lower in the combined treatment group as early as week 2.

Investigators noted that patients with less refractory depression did better with tDCS—an observation also seen in recent trials of rTMS—but, interestingly, those with melancholic depression seemed to respond well to combined treatment. Adverse effects were low, with seven cases of treatment-emergent mania or hypomania, five of which were in the combined treatment group, and mild skin redness in 25% of patients receiving tDCS (Brunoni AR et al, JAMA Psych 2013; ePub ahead of print).

TCPR’s Take: This study demonstrates the antidepressant efficacy of tDCS, an effect that’s even greater when combined with sertraline. Although the tDCS protocol was intense and impractical for most patients (daily sessions of 20 or 30 minutes for two weeks) and the 50 mg/day dose of sertraline may have been too low for those who received only medication, future research will hopefully address changes in these parameters. The authors also plan to study whether maintenance tDCS offers any prolonged benefit, and whether patients in this study who received sham treatment might improve when switched to tDCS.