Accelerated Optimized Protocol of Intermittent Theta-Burst Stimulation for Negative Symptoms in Schizophrenia (ACTh-NS): A Randomized, Double-Blind, Sham-Controlled Study Design.

Abstract

Introduction: Intermittent theta burst stimulation (iTBS) has been associated with improvements in the negative symptoms (NSs) of schizophrenia. However, optimizing by shorter protocols remains necessary. Furthermore, understanding their impact on other clinical symptoms, sleep, and autonomic regulation is important to underlying therapeutic effects.

Objectives: Evaluate the efficacy of an accelerated iTBS protocol on reducing NSs in patients with schizophrenia. We hypothesize a 20% reduction in BNSS scores in the active group, as well as improvements in disorder-related aspects, including sleep patterns, symptoms severity, and cognition.

Methods: A double-blind, randomized, sham-controlled clinical trial design will be conducted to test the effects of the accelerated iTBS protocol in 60 participants with schizophrenia (30 active and 30 sham) with moderate NSs. iTBS protocol will consist of four daily sessions, with 600 pulses per session for five consecutive days. Patients will be assessed at three time points (baseline, after intervention and 30 days follow up) for clinical symptoms, cognition and heart rate variability. The primary outcome will be negative symptoms using the Brief Negative Symptom Scale (BNSS). Study register: Brazilian Registry of Clinical Trials (CAEE: 71102823.4.0000.5505).

Conclusions: The accelerated iTBS protocol has demonstrated promising effects on NSs. However, it is still necessary to establish an effective and feasible high-dosage protocol. This study will contribute to optimizing therapeutic protocols for schizophrenia, with a particular focus on clinical applicability. Additionally, it will provide an opportunity to deepen the understanding of the physiological effects of neuromodulation, contributing to the understanding of its underlying mechanisms.