Effect of high-frequency rTMS on cognitive deficits in schizophrenia: A randomized, double blind, sham-controlled trial.

Background: Cognitive deficits significantly contribute to the disability related to schizophrenia.

Aim: We aim to evaluate the efficacy of high-frequency rTMS intervention in the improvement of cognitive symptoms in schizophrenia.

Methods: One-hundred patients of predominantly negative schizophrenia having cognitive deficits were enrolled for this randomized, sham controlled, double-blind trial. Active group received 20 sessions of rTMS at 20 Hz frequency and 100% motor threshold with total 2000 pulses over 4 weeks. Those receiving 5 consecutive rTMS sessions were included in primary and safety analysis. The trial protocol was registered with the Clinical Trials Registry - India (CTRI/2019/05/019099). An intention to treat (ITT) analysis was conducted for the intervention.

Results: A total of 497 patients were screened, with 100 randomized to active (n = 50) and sham (n = 50) rTMS groups. Baseline demographic and clinical characteristics were comparable between groups. The mean total scores and dysfunction ratings on the PGI Memory Scale, as well as performance on other cognitive measures, did not differ significantly between active and sham groups at any assessment point. Within the active rTMS group, significant improvements over time were observed in total dysfunction rating ( = 0.018), delayed recall ( = 0.042), immediate recall ( = 0.039), and verbal retention of dissimilar pairs ( = 0.014). A significant between-group difference was found only for remote memory change at 1-month follow-up ( = 0.016). Two adverse events were reported in the active group (one partial seizure, one case of aggravated psychosis), leading to discontinuation of intervention; no serious adverse events occurred in the sham group.

Conclusions: High-frequency rTMS resulted in modest improvement in specific cognitive measures, most notably remote memory in the active group at 1-month follow-up, but did not demonstrate significant overall group differences in cognitive outcomes compared to sham. It builds ground for further research assessing for delayed effects using neuronavigational methods.