Efficacy and Safety of Accelerated Intermittent Theta Burst Stimulation (aiTBS) for Negative Symptoms of Schizophrenia: A Randomised Controlled Trial

Schizophrenia has negative symptoms, including anhedonia, avolition, asociality, affect blunting and alogia, associated with high disability rates. Around 33% of schizophrenia patients do not fully respond to antipsychotic pharmacotherapy, and patients with predominantly negative symptoms more resistant to treatment. Recent meta-analysis of 57 studies involving 2633 schizophrenia patients revealed that Repetitive Transcranial magnetic stimulation (rTMS) had superior efficacy in alleviating negative symptoms compared with sham interventions. Intermittent theta burst stimulation (iTBS) has been approved for the treatment of depression and explored for negative symptoms among patients with schizophrenia. Evidence suggests that accelerated iTBS protocols over the left dorsolateral prefrontal cortex (L-DLPFC) with multiple daily sessions over a short span are safe, with faster clinical improvement. However, available evidence appears insufficient to support a robust recommendation in leading treatment guidelines for negative symptoms. Thus, the effectiveness of accelerated iTBS in ameliorating the negative symptoms of schizophrenia requires more investigation. Although previous trials demonstrated the relationship between cortical activity measured by fNIRS and symptoms of schizophrenia, no study has attempted to determine whether neural activity of specific regions, measured by fNIRS, would predict clinical benefits of aiTBS on negative symptoms in schizophrenia