A Little Juice to the Brain Eases Depression
By Crystal Phend, Senior Staff Writer, MedPage Today
Published: February 06, 2013
Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania
Note that this single-center, randomized, controlled trial demonstrated a benefit to the combination of electrical current therapy and sertraline in the treatment of major depression.
Be aware that long-term results have not been published; it is unclear if the benefit of electrical current therapy will persist after the active treatment phase.
Noninvasive, electric stimulation of the brain appears to help the initial phase of treatment in major depressive disorder, especially in combination with an antidepressant, a double-blind trial showed.
Six weeks of daily transcranial direct current stimulation sessions reduced depression scores roughly the same as sertraline (Zoloft, P=0.35), Andre R. Brunoni, MD, PhD, of the University of São Paulo, Brazil, and colleagues reported online in JAMA Psychiatry.
The two together brought scores down by an average 8.5 points more than sertraline alone on a depression rating scale, and by 5.9 points more than direct current stimulation alone (P=0.002 and P=0.03, respectively).
A 3-point difference on that Montgomery-Asberg Depression Rating Scale (MADRS) is considered clinically relevant.
"Noninvasive brain stimulation is becoming an established therapy for the treatment of depression," Brunoni and colleagues wrote.
The weak electrical current applied across large electrodes on the scalp may work by boosting activity in an area of the brain known to be hypoactive in depression, with the advantage of not having the same adverse effects and contraindications as antidepressant drugs, the group pointed out.
The device also is relatively inexpensive, so it might be a "cost-effective alternative for regions with low resources where the prevalence of major depressive disorder is high, such as most developing nations," they added.
However, the treatment is less practical than taking a pill, and it's not clear how its results would hold up in the maintenance phase.
"Even if transcranial direct current stimulation becomes available for in-house use, it would still require 20- to 30-minute daily sessions for several weeks," Brunoni's group wrote.
Their Sertraline vs Electrical Current Therapy for Treating Depression Clinical Study (SELECT TDCS) compared in a two-by-two design treatment with 6 weeks of sertraline at 50 mg per day or placebo and 2-mA anodal left/cathodal right prefrontal transcranial direct current stimulation (30-minute sessions each weekday plus two extra sessions every other week) or sham.
It included 120 antidepressant-naive patients with moderate-to-severe major depressive disorder but no psychotic or bipolar component, seen at a single outpatient center in an academic setting in São Paulo. The cohort had a relatively low degree of refractoriness and short duration of the index episode.
The only thing that wasn't better than inactive treatment at the end of the 6-week period was sertraline alone, with a mean difference of 2.9 points versus placebo (P=0.20).
The explanation may have been that 50 mg per day was a low dose for some participants, though there have been negative trials with sertraline in major depressive disorder, the researchers pointed out.
Transcranial direct current stimulation improved MADRS score by 5.6 points over sham (P=0.01).
The combination of the two appeared to work fastest, as that was the only group with a significant change in score at week two. Factorial analysis suggested that the initial effect was driven primarily by the electric stimulation treatment.
The two appeared to be additive rather than synergistic.
Clinical response with at least a 50% reduction in baseline MADRS score was significantly more common with transcranial direct current stimulation or combination treatment than with placebo (43% and 63% versus 17%).
Remission, with MADRS score falling to 10 points or less, occurred in 47% of the combo group and 40% of the electrical stimulation group, which were both significantly better than the 13% rate with placebo.
Sertraline alone induced remission in 30%, although this difference didn't reach significance.
No negative cognitive effects were seen with transcranial direct current stimulation, though skin redness was more common at the end of week two.
Of the seven episodes of treatment-emergent mania or hypomania, five were in the combined treatment group, including one severe manic episode requiring pharmacologic intervention.
Mania or hypomania induction may be similar with transcranial direct current stimulation as with antidepressants, so such events need careful monitoring in future trials, Brunoni's group noted.
Further research is needed into longer-term effects and into use in the inpatient setting, they added.
Their trial includes an open-label phase for sham nonresponders to cross over to 10 days of active transcranial direct current stimulation, as well as a 6-month follow-up phase for those who responded to active treatment in the first 6 weeks.