Transcranial Direct Current Stimulation for Negative Symptoms of Schizophrenia: Why the Reader Must Choose a Clinically Relevant Outcome

Abstract

A recent, large, randomized controlled trial (RCT) of 10 twice-daily sessions of active vs sham transcranial direct current stimulation (tDCS), delivered across 5 consecutive days to schizophrenia patients with high negative symptom burden, found that active treatment was superior to sham treatment by a mean of 2.65 points on the Positive and Negative Syndrome Scale, negative subscale (PANSS-N), at 6 weeks. This was the primary endpoint of the study. Because a difference of 2.65 PANSS-N points between the average active vs sham tDCS patient is a very small advantage, it appears that the finding was statistically but not clinically significant; why this is so is explained in the context of how the PANSS-N is scored. The study also found that, with response defined as 20% attenuation of PANSS-N scores, significantly more (40% vs 4%) active than sham group patients responded at 6 weeks. This was one of many secondary outcomes that the study examined. Because response is a clinically important endpoint, it appears that the finding was clinically as well as statistically significant; why this is so is also explained in the context of PANSS-N scoring. As a final poser, whereas the advantage for active tDCS for both outcomes persisted at 12 weeks, at neither 6 nor 12 weeks was active treatment superior to sham treatment on a global measure of functioning; this suggests that the advantage for active tDCS does not translate into real-life gains. The reader is provided with an understanding of how to critically read a paper that describes an RCT; of how to interpret a continuous outcome measure that describes the average patient versus a categorical outcome measure that describes a clinically important outcome in an entire group; and, most important of all, of the need to choose an outcome that is relevant to clinical practice.