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04. Efficacy and Safety of Transcranial Direct Current Stimulation for Treating Negative Symptoms in Schizophrenia

Published on July 1, 2020 Expired on April 1, 2023

James Phelps, M.D.

Research Editor - Psychopharmacology Institute

Key Points

  • Is transcranial direct current stimulation for negative symptoms in schizophrenia a good idea? The data so far are mixed but not entirely discouraging. Here is a recent review, an older meta-analysis, and a nifty electrode placement guide if you are going to use this.

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You are likely familiar with repetitive transcranial magnetic stimulation, rTMS. One of my colleagues even bought her machine for her solo office practice. You may also have seen that transcranial direct current stimulation is getting nearly as much study now. Here is a new study that might make you want to buy a device and start using it if you see many patients with schizophrenia. This time, we will look at a new randomized trial of transcranial direct current stimulation that just came out in JAMA Psychiatry. It is quite exciting because negative symptoms of schizophrenia can limit the quality of life. Moreover, a quick peek at the outcomes of this study suggests that it can help. So, let’s take a closer look.

First of all, what exactly is transcranial direct current stimulation? Well, there are devices on the internet for as little as $150. However, research teams use more sophisticated devices that allow positioning both the target and reference electrodes very deliberately. One form of stimulation depolarizes neurons and another hyperpolarizes them. So, manipulations can go in 2 directions, increasing regional activity or decreasing it, depending on electrode placement and current flow. This is not an electrotherapy device, where you clip electrodes on the earlobes and pass current from one to the other. It is not placing electrodes over the temples with a headband. It is more deliberate placement, with the anode centered over the left dorsolateral prefrontal cortex and the cathode over the left temporoparietal junction with a standard 2 mA of current. That is what this team did for the treatment of negative symptoms of schizophrenia: Left dorsolateral, prefrontal cortex (PFC), and the left temporoparietal junction.

Now, there have been several previous trials of direct current stimulation for negative symptoms in schizophrenia, and the results were mostly mixed. A team from the University of Sao Paulo set out to replicate one of the most positive studies. Moreover, there have been mixed findings before this one, which means that a new study—even like this one, which I am excited about, it should have stunning results—needs to be understood even still as part of a bigger, more complex picture.

So, what did the researchers find? Well, on the PANSS (Positive and Negative Symptoms of Schizophrenia Scale) overall, patients receiving active transcranial direct current stimulation had a statistically more significant reduction in their PANSS scores than those receiving sham treatment. It was the same setup, without 2 mA of current. The difference was 2.65 points on just the negative symptom subscale. So, if a PANSS score difference of 5 points is worth paying attention to, which is the standard, a difference in just the negative symptom subscale of 2.65 points is worthy of attention. In other words, this is a clinically significant change, at least as best we can tell from the literature.

Consumer versions of these devices cost as little as $150. With care, you could find one that would allow you to use the same precise electrode placements. In theory, you could buy one of these and try it with some patients at a little cost and slight risk. Adverse effects, for example in this study, 42% of the active group had a burning sensation on their scalp. However, it was minimal enough that they were only slightly better than the sham group at guessing after the study which group they were in. It did not lead to treatment discontinuation. Otherwise, there were no problems more severe than sham, and none that were serious—such a low cost. This looks like slight risk, shallow risk one might say.

To summarize, then, this randomized trial suggests that with transcranial direct current stimulation, 2 mA via an anode over the left dorsolateral prefrontal cortex, is more effective than sham treatment for decreasing negative symptoms of schizophrenia. If I were working in a clinic for people with severe mental illness, I think I would look into buying a device and beginning to try it with select patients. To learn more, first, you will have to research the various devices available, and there is quite a bit on the internet about that. And then, for electrode placement, there is a lovely rotatable 3-dimensional guide to find those specific points. F3 and T3 are the specific placement points. That is linked here from the Psychopharmacology Institute’s website for this Quick Take.

Abstract

Efficacy and Safety of Transcranial Direct Current Stimulation for Treating Negative Symptoms in Schizophrenia A Randomized Clinical Trial

Leandro da Costa Lane Valiengo, MD, PhD; Stephan Goerigk, MSc; Pedro Caldana Gordon, MD, PhD; Frank Padberg, MD; Mauricio Henriques Serpa, MD; Stephanie Koebe, BSc; Leonardo Afonso dos Santos, MD; Roger Alberto Marcos Lovera, MD; Juliana Barbosa de Carvalho, BSc; Martinus van de Bilt, MD, PhD; Acioly L. T. Lacerda, MD, PhD; Helio Elkis, MD, PhD; Wagner Farid Gattaz, MD, PhD; Andre R. Brunoni, MD, PhD

IMPORTANCE: Negative symptoms represent a substantial burden in schizophrenia. Although preliminary studies have suggested that transcranial direct current stimulation (tDCS) is effective for some clusters of symptoms, the clinical benefits for negative symptoms are unclear.

OBJECTIVE: To determine the efficacy and safety of tDCS vs sham as an add-on treatment for patients with schizophrenia and predominant negative symptoms.

DESIGN, SETTING, AND PARTICIPANTS: The double-blind Schizophrenia Treatment With Electric Transcranial Stimulation (STARTS) randomized clinical trial was conducted from September 2014 to March 2018 in 2 outpatient clinics in the state of São Paulo, Brazil. Patients with schizophrenia with stable negative and positive symptoms and a minimum score of 20 points in the negative symptoms subscale of the Positive and Negative Syndrome Scale (PANSS) were included.

INTERVENTIONS: Ten sessions of tDCS performed twice a day for 5 days or a sham procedure. The anode and the cathode were positioned over the left prefrontal cortex and the left temporoparietal junction, respectively.

MAIN OUTCOMES AND MEASURES: Change in the PANSS negative symptoms subscale score at week 6 was the primary outcome. Patients were followed-up for an additional 6 weeks.

RESULTS: Of the 100 included patients, 20 (20.0%) were female, and the mean (SD) age was 35.3 (9.3) years. A total of 95 patients (95.0%) finished the trial. In the intention-to-treat analysis, patients receiving active tDCS showed a significantly greater improvement in PANSS score compared with those receiving the sham procedure (difference, 2.65; 95% CI, 1.51-3.79; number needed to treat, 3.18; 95% CI, 2.12-6.99; P < .001). Response rates for negative symptoms (20% improvement or greater) were also higher in the active group (20 of 50 [40%]) vs the sham group (2 of 50 [4%]) (P < .001). These effects persisted at follow-up. Transcranial direct current stimulation was well tolerated, and adverse effects did not differ between groups, except for burning sensation over the scalp in the active group (43.8%) vs the sham group (14.3%) (P = .003).

CONCLUSIONS AND RELEVANCE: Transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia.

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Reference

Valiengo, L. D., Goerigk, S., Gordon, P. C., Padberg, F., Serpa, M. H., Koebe, S., Santos, L. A., Lovera, R. A., Carvalho, J. B., Van de Bilt, M., Lacerda, A. L., Elkis, H., Gattaz, W. F., & Brunoni, A. R. (2020). Efficacy and safety of transcranial direct current stimulation for treating negative symptoms in schizophrenia. JAMA Psychiatry, 77(2), 121.

Placements. (2020, March 8). focus – take charge. https://foc.us/placements/

Learning Objectives:

After completing this activity, the learner will be able to:

  1. Reassess the role of antidepressants in the treatment of bipolar depression in light of a new review and new data suggesting that antidepressants could induce treatment resistance.
  2. Compare current treatment options for adolescents with anorexia nervosa.
  3. Evaluate a randomized trial which purports to show memantine improved memory outcomes in older patients with depression when used as an adjunct to escitalopram.
  4. Examine the literature on the use of transcranial Direct Current Stimulation (tDCS) for negative symptoms in patients with schizophrenia. 
  5. Evaluate recent and older data on the use of repetitive transcranial magnetic stimulation for the treatment of auditory hallucinations in patients with schizophrenia.

Original Release Date: July 1, 2020

Review and Re-release Date: March 1, 2023

Expiration Date: April 1, 2023

Relevant Financial Disclosures: 

James Phelps declares the following interests:

- McGraw-Hill:  book on bipolar disorder

- W.W. Norton & Co.:  book on bipolar disorder

All of the relevant financial relationships listed above have been mitigated by Medical Academy and the Psychopharmacology Institute.

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