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Direct current is inferior to SSRI? A RCT.

This paper was published in an important journal and the related editorial notes some flaws, particularly around an inability to know what is the correct dose of direct current stimulation. What the editorial notes is something I also saw: that direct current stimulation worked against placebo on response remission, and probably MADRS scores.

Outcomes matter. But this is not in the analysis.


In a single-center, double-blind, noninferiority trial involving adults with unipolar depression, we randomly assigned patients to receive tDCS plus oral placebo, sham tDCS plus escitalopram, or sham tDCS plus oral placebo. The tDCS was administered in 30-minute, 2-mA prefrontal stimulation sessions for 15 consecutive weekdays, followed by 7 weekly treatments. Escitalopram was given at a dose of 10 mg per day for 3 weeks and 20 mg per day thereafter. The primary outcome measure was the change in the 17-item Hamilton Depression Rating Scale (HDRS-17) score (range, 0 to 52, with higher scores indicating more depression). Noninferiority of tDCS versus escitalopram was defined by a lower boundary of the confidence interval for the difference in the decreased score that was at least 50% of the difference in the scores with placebo versus escitalopram.

A total of 245 patients underwent randomization, with 91 being assigned to escitalopram, 94 to tDCS, and 60 to placebo. In the intention-to-treat analysis, the mean (±SD) decrease in the score from baseline was 11.3±6.5 points in the escitalopram group, 9.0±7.1 points in the tDCS group, and 5.8±7.9 points in the placebo group. The lower boundary of the confidence interval for the difference in the decrease for tDCS versus escitalopram (difference, ?2.3 points; 95% confidence interval [CI], ?4.3 to ?0.4; P=0.69) was lower than the noninferiority margin of ?2.75 (50% of placebo minus escitalopram), so noninferiority could not be claimed. Escitalopram and tDCS were both superior to placebo (difference vs. placebo, 5.5 points [95% CI, 3.1 to 7.8; P<0.001] and 3.2 points [95% CI, 0.7 to 5.5; P=0.01], respectively). Patients receiving tDCS had higher rates of skin redness, tinnitus, and nervousness than did those in the other two groups, and new-onset mania developed in 2 patients in the tDCS group. Patients receiving escitalopram had more frequent sleepiness and obstipation than did those in the other two groups.

In a single-center trial, tDCS for the treatment of depression did not show noninferiority to escitalopram over a 10-week period and was associated with more adverse events,
N Engl J Med 2017; 376:2593-2594

But consider not the abstract. Consider this graph. Note that there is very little difference between DCS and medication: it is just significant. There is a singificant improvement in MADRS and response rate.

When you look at the other depression scales, the difference with escitalopram is higher, in part because of the measurement of anxiety symptoms. But consider the response rate (the same thing happens with remission. Put simply, both work, and there is not a significant difference.

There is more here than the authors suggest. Their design — non inferiority — is under powered so to not find a difference between the two active treatments. Expect more studies like this, and look at the supplementary data, for modern editors are moving as much as possible from the printed page.

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