A randomized, double blind, sham-controlled trial of repetitive transcranial magnetic stimulation (rTMS) in the treatment of negative symptoms in schizophrenia

Brain Stimul. 2020 May-Jun;13(3):840-849. doi: 10.1016/j.brs.2020.02.016. Epub 2020 Feb 29.


Background: Research has implicated hypofrontality in the pathogenesis of Negative symptoms of schizophrenia.These symptoms are often resistant to treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) has been shown to reverse this hypofrontality. Higher frequency rTMS has shown better promise, but so far there has been very little research in this area.

Objective: We aimed to evaluate the efficacy of high-frequency (20 Hz) unilateral rTMS over the left Dorso-Lateral Pre-frontal Cortex (DLPFC) in the improvement of Negative symptoms in Schizophrenia.

Methods: 100 patients of schizophrenia with predominantly negative symptoms, were enrolled for this randomized, sham-controlled, double-blind trial.Each participant received 20 sessions of rTMS at 20 Hz frequency and 100% motor threshold, via either the active or the sham coil, over 4 weeks. A total of 2000 pulses were imparted in 10 trains per session. Negative symptoms were assessed with the SANS and PANSS. CDSS was used to rule out depressive symptoms. Assessments were carried out at baseline, post-intervention, and 1-month, 2-months, 3-months and 4-months follow ups.

Results: The improvement in the negative symptoms (Anhedonia, Alogia, Avolition, Attention impairment) in active group was statistically significant at 0.01 and 0.05 (p-value) as compared to sham group.

Conclusions: These results suggest that high-frequency rTMS may lead to improvement in negative symptoms of schizophrenia. It may be worth considering its use as an adjunct to pharmacological treatment of negative symptoms.

Keywords: Negative symptoms; Repetitive transcranial magnetic stimulation; Schizophrenia; rTMS.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anhedonia / physiology
  • Apathy / physiology
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Prefrontal Cortex / physiology*
  • Schizophrenia / diagnosis*
  • Schizophrenia / therapy*
  • Schizophrenic Psychology*
  • Transcranial Magnetic Stimulation / methods*
  • Treatment Outcome