Is combining direct electrical stimulation with antidepressants more effective in depression? :JAMA Psy.April.2013


Recent times have witnessed a surge in research on Transcranial Direct Current Stimulation (tDCS). Trials in 1960s produced mixed results and though approved  for clinical use in many countries, (USA Israel, Canada, and Brazil etc),it has not been widely adopted in clinical settings.

The treatment involves application of weak, direct electrical current to the brain through  large electrodes  placed over the scalp. Anodal and cathodal stimulation increases and decreases cortical excitability, respectively.It is thought that this will induce significant long- lasting neuroplastic effects.Left dorsolateral prefrontal cortex (DLPFC) is hypoactive in depression and, anodal tDCS would  increase activity in this area and thus restore prefrontal activity. Recent studies show  mixed clinical results. Evidence for neurogenesis is emerging. A recent meta-analysis suggested that the technique might be effective for depression, but further trials are necessary for firm conclusions.

Andre R. Brunoni and colleagues from Brasil report the results of large RCT  with 120 participants having non psychotic depression. tDCS plus sertraline was compared against either alone.Participants were randomized to 4 groups: sham tDCS and placebo ( placebo), sham tDCS and sertraline (sertraline only), active tDCS and placebo (tDCS only), and active tDCS and sertraline (combined treatment).

Intervention entailed a short-term treatment period in which ten  30- minute  tDCS sessions were given to subjects in the first two weeks followed by single stimulation sessions on week 4 and week 6 . Patients  thus received total of 12 sessions. Study was continued as open label after this RCT phase.Stimulation (Brifrontal) was done with electrodes placed on areas corresponding to left and right DLPFC using a direct current of 2 mA for 30 min/d for 10 days, followed by 2 extra tDCS sessions every other week until the study end point (total charge density of 1728 coulombs/m2).Pharmacological intervention was a fixed dose of sertraline  50 mg/d.The primary efficacy outcome was the Montgomery-Asberg Depression Rating Scale (MADRS) score at 6 weeks.


Combined treatment differed significantly from placebo (mean difference, 11.5 points; 95% CI, 6.03 to 17.10; P=.001), tDCS only (mean difference, 5.9 points; 95% CI, 0.36 to 11.43; P = .03), and Sertraline only (mean difference, 8.5 points; 95% CI, 2.96 to 14.03; P=.002).No difference was observed between tDCS only and sertraline only. Greater response seen in patients with melancholic depression.resistant cases showed less response. greater baseline severity showed greater response to the combined treatment. Benzodiazepine use, even in low dosages, induced lower effects in the tDCS-only group.

 Conclusions: Combined treatment is more effective.tDCS is comparable to antidepressant. The efficacy of tDCS appeared to be greater compared with recent rTMS trials. tDCS is not associated with hazardous cognitive effects.

Limitations: Dose of Sertraline used is very low. The intervention require 20- to 30-minute daily sessions for several weeks (practical limitations). There were 7 episodes of treatment-emergent mania or hypomania, 5 of which occurred in the combined treatment group.


Confidence Interval:  CI  shows how “good” an estimate is ie how sure we are that the estimate of effect  will fall in the given range. In this study, we are 95% confident that the combined treatment will reduce the depression symptom score by a measure between 6.03 and 17.10 points. ie  if we repeated the trial for similar samples  (taken from the general population of patients with depression), then 95% of the estimates arising from those trials will be with in this range.

 Summary of the article:

 The Sertraline vs Electrical Current Therapy for Treating Depression Clinical Study: Results From a Factorial, Randomized, Controlled Trial.

Brunoni AR, Valiengo L, Baccaro A, Zanão TA, de Oliveira JF, Goulart A, Boggio PS, Lotufo PA, Benseñor IM, Fregni F.JAMA Psychiatry. 2013 Apr 1;70(4):383-91.

2 thoughts on “Is combining direct electrical stimulation with antidepressants more effective in depression? :JAMA Psy.April.2013

  1. Is 50 mg of Sertraline a “very low” dose??

    ‘ZOLOFT’ – FDA Approved prescribing indication–
    Dosage for Adults – Initial Treatment
    Major Depressive Disorder & OCD–ZOLOFT treatment should be administered at a dose of 50 mg once daily.
    Patients not responding to a 50 mg dose MAY benefit from dose increases up to a maximum of 200 mg/day. “

    • It is a starting dose only. In this cohort 20% were considered resistant cases to start with .if the team used modest dose , might have been more encouraging

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