Although a study of prefrontal transcranial direct current stimulation (tDCS) was not shown to be significantly effective in supporting cognitive behavioral therapy (CBT) in depression, investigators discovered a biomarker that explains tDCS response variability and could be used to guide patient selection in future clinical trials, according to a study published in Neuropsychopharmacology.

For many patients with depression, standard treatments such as antidepressants and CBT are ineffective. This mechanistic double-blind, randomized controlled trial was performed to assess the efficacy of prefrontal tDCS for patients with major depressive disorder. Prior to CBT sessions, patients (n=71 approached and n=39 randomized) were given 8 weekly sessions of tDCS to the left prefrontal cortex. End points were to determine if tDCS improved CBT efficacy relative to sham stimulation and if neural measures could predict clinical response, defined as a 50% or greater reduction on the Hamilton Rating Scale for Depression (HAM-D).

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A modest, nonsignificant effect of tDCS on clinical outcome over and above CBT was found (active: 50%; sham: 31.6%; odds ratio 2.16; 95% CI, 0.59-7.99), and a strong relationship between baseline activation in the stimulated prefrontal region during a working memory task and symptom improvement was found. When symptom outcome analyses were repeated with the sample split according to this biomarker, it was shown that tDCS was significantly more effective than sham in participants with high activation in the left prefrontal cortex at baseline. Using this measure, investigators were able to predict clinical response with 86% accuracy. Furthermore, exploratory analyses showed several other brain regions where baseline activation was associated with subsequent response to CBT, regardless of tDCS treatment.

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Researchers concluded that while these findings do not support the use of tDCS as an adjunct to CBT in major depressive disorder, there was the discovery of “ … a biomarker explaining variability in tDCS response: baseline activation in the area of stimulation (L-DLPFC).” This biomarker appeared to be “… relatively strong and specific to active stimulation.” Additionally, researchers noted that the data collected “… speak to the potential utility of neuroscience techniques in developing novel mental health interventions; incorporating cognitive neuroscience measures into clinical trials could allow simultaneous assessment of clinical efficacy and detection of potential biomarkers of treatment response. Ultimately, these data could guide patient selection in larger clinical trials, and, if confirmed, inform clinical use of tDCS in depression.”

Nord CL, Halahakoon DC, Limbachya T, et al. Neural predictors of treatment response to brain stimulation and psychological therapy in depression: a double-blind randomized controlled trial [published online April 30, 2019]. Neuropsychopharmacology. doi: 10.1038/s41386-019-0401-0