Noninvasive Brain Stimulation Plus SSRI Effective for MDD

Caroline Cassels

February 06, 2013

Combination treatment with transcranial direct current stimulation (tDCS) and a commonly used selective serotonin reuptake inhibitor (SSRI) is more effective than either treatment alone for major depressive disorder (MDD), new research shows.

Further, the double-blind trial revealed that the 2 treatments have similar safety and efficacy profiles.

"In MDD, the combination of tDCS and sertraline increases the efficacy of each treatment. The efficacy and safety of tDCS and sertraline did not differ," the authors, led by Andre R. Brunoni, MD, PhD, University Hospital, University of São Paulo in Brazil, write.

The study was published online February 6 in JAMA Psychiatry.

Need for Better Treatments

According to investigators, there is a pressing need for "safe, effective, affordable therapies for MDD."

Standard treatments with antidepressant medications are only moderately effective, and treatments such as repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT) can be expensive and have significant adverse effects that "limit their availability and applicability."

The authors explain that with tDCS, a "simple method of brain stimulation," weak, direct electrical current is applied to the brain through electrodes placed over the scalp, where "anodal and cathodal stimulation increases and decreases cortical excitability, respectively."

The investigators note that the antidepressant effects of tDCS are based on the finding that the "left dorsolateral prefrontal cortex (DLPFC) is hypoactive in patients with MDD and, therefore, anodal tDCS would be able to restore prefrontal activity by increasing activity in this area."

Recent research has also shown that the effects of tDCS can be further enhanced or diminished with medication.

The researchers hypothesized that combined treatment with tDCS and the SSRI sertraline would have greater efficacy than either treatment alone. Further, they assessed whether the combination of these interventions was additive or synergistic.

The study included 120 patients free of antidepressants who had moderate to severe nonpsychotic unipolar MDD. The patients were recruited at a single academic center. The study's primary outcome measure was a change in the Montgomery-Ǻsberg Depression Rating Scale (MADRS) score at 6 weeks. A difference of 3 points was considered to be clinically relevant.

The study included 3 phases. In the first phase, patients were randomly assigned to 1 of 4 treatment groups:

  • Placebo: Sham tDCS plus placebo

  • Sertraline only: Sham tDCS plus sertraline

  • tDCS only: tDCS plus placebo

  • Combined treatment: Active tDCS plus sertraline

In the first phase of the study, participants received 10 30-minute sessions during weekdays and a single 30-minute treatment at 2- and 4-week follow-up.

The other 2 study phases were an open-label, crossover phase in which sham tDCS nonresponders received 10-day active tDCS and a 6-month follow-up phase in which tDCS responders received maintenance tDCS alone or in combination with sertraline if they were in the combined treatment group.

At 6 weeks, the researchers found that there was a significant difference in MADRS scores between the combined treatment group vs sertraline alone (mean difference, 8.5 points; 95% confidence interval [CI], 2.96 - 14.03; P = .002).

For the group receiving only tDCS, the mean difference in MADRS score was 5.9 points (95% CI, 0.36 - 11.43; P = 0.3), and for placebo/sham tDCS, the mean difference was 11.5 points (95% CI, 6.03 - 17.10; P < .001).

The researchers found that the efficacy of tDCS alone vs sertraline alone was comparable, with a mean difference of 2.6 points (95% CI, -2.90 to 8.13; P = .35).

Use of tDCS only, but not sertraline only, was superior to placebo/sham tDCS.

Mania, Hypomania a Potential Concern

With the exception of skin redness on the scalp with active tDCS, the researchers report that sertraline and active tDCS had similar side effect profiles. However, they note there were 7 episodes of treatment-emergent mania or hypomania, 5 of which occurred in the combined treatment group.

The researchers indicate that noninvasive brain stimulation is becoming an established treatment for depression, noting that repetitive transcranial magnetic stimulation (rTMS) is already approved for clinical use in several countries.

They suggest that because tDCS is "relatively inexpensive," future research should focus on whether it might be a cost-effective treatment in "regions with low resources where the prevalence of MDD is high, such as most developing nations."

"In addition to confirming the clinical efficacy of tDCS and demonstrating that tDCS has effects similar to those of sertraline in antidepressant-free patients with MDD, we observed that tDCS and sertraline combined have greater response compared with each intervention alone, although the increased risk of mania or hypomania should be considered," the investigators conclude.

The authors have disclosed no relevant financial relationships.

JAMA Psychiatry. Published online February 6, 2013. Abstract