Transcranial direct current stimulation and sertraline together improve symptoms of depression significantly more effectively than either treatment alone.
A randomized controlled trial suggests that the treatments potentiate each other, Dr. Andre R. Brunoni and his colleagues wrote in the Feb. 6 online issue of JAMA Psychiatry (formerly Archives of General Psychiatry).
"The findings that the combined treatment was associated with a faster, greater response could indicate that each intervention has a distinct but additive mechanism of action," wrote Dr. Brunoni of the Clinical Research Center, University Hospital, São Paolo, Brazil, and his coauthors.
Transcranial direct current stimulation (tDCS) is a technique in which weak and direct electrical currents are applied to the brain through electrodes that are placed on the scalp. The antidepressant effects of tDCS "are based on the finding that the left dorsolateral prefrontal cortex is hypoactive in depression, and, therefore, anodal tDCS would be able to restore prefrontal activity by increasing activity in this area."
In light of the association between major depressive disorder and not only lateralized cortical dorsolateral prefrontal lobe dysfunction but also limbic subcortical dysfunction, Dr. Brunoni and his colleagues hypothesized that tDCS could act primarily in cortical activation, whereas selective serotonin reuptake inhibitors would act primarily on the down-regulation of limbic hyperactivity.
"In fact, a recent systematic review compared neuroimaging findings from psychological vs. pharmacological interventions, suggesting that the former were related to top-down (frontal activation) effects, whereas the latter were associated with bottom-up effects," they wrote.
The 6-week trial enrolled 120 patients with unipolar nonpsychotic major depressive disorder. They were randomized to four intervention groups: sertraline with sham tDCS, tDCS with placebo medication, placebo only (sham tDCS and placebo medication), and active tDCS with sertraline 50 mg/day. The tDCS applications consisted of ten 30-minute treatments in the first 10 days, followed by 2 additional sessions per week for the remainder of the study. The primary outcome was the Montgomery-Åsberg Depression Ratings Scale (MADRS) (JAMA Psychiatry 2013 Feb. 6 [doi: 10.1001/2013.jamapsychiatry.32]).
The combination treatment was significantly more effective than placebo, with a mean difference of 11.5 points in MADRS scores. The combination therapy also was significantly more effective than tDCS only (mean difference 5.9 points) and sertraline only (mean difference 8.5 points). No difference was found between the sertraline and tDCS only groups. These findings suggest that the two treatments exert a synergistic effect, the authors said.
The combination treatment also was associated with a quick response. At 2 weeks, there was already a significant MADRS score improvement in these patients (–48.5%), compared with placebo (–30%), sertraline only (–29%), and tDCS only (–34%).
There were five episodes of hypomania and two of clinical mania. Most of these (5) occurred in the combined treatment group.
The study was funded by the São Paulo Research Foundation. None of the investigators reported any financial disclosures.