Schizophrenia patients commonly present with persistent negative symptoms which remain the main reason for dysfunction after recovery from an acute episode of psychotic symptoms. Negative symptoms in schizophrenia exact significant burden with no effective pharmacological or behavior treatment options thus far. Neuromodulatory modalities present a novel and alternative treatment approach and recent trials have shown preliminary evidence for the efficacy of intermittent Theta Burst Stimulation (iTBS) to treat negative symptoms in schizophrenia. In this study, we aim to examine the effectiveness of an accelerated iTBS treatment protocol as an augmentation treatment regime for patient in rehabilitation care with persistent negative symptoms.

We propose a pragmatic, open label and single arm clinical trial. Forty patients with diagnosis of schizophrenia, who had been stabilized from psychotic symptoms and currently suffering from dominant negative symptoms will be recruited and undergo accelerated iTBS treatment for 5 consecutive sessions each day for 5 working days. Participants will be followed up immediately, 1 month and 3 months after the end of treatment. Clinical assessment includes, BNSS, The Brief Negative Symptom Scale; SANS, Scale for the assessment of negative symptoms; SAPS, Scale for the assessment of positive symptoms; PANSS, Positive and Negative Symptoms Scale; MoCA, Montreal Cognitive Assessment scale; CDSS, Calgary Depression Scale for Schizophrenia: SDS, Sheehans' disability scale and EQ-5D. The primary endpoint of the trial is the change of negative symptoms as assessed by PANSS, negative symptoms subscale immediately after the treatment.

This study will determine whether accelerated iTBS is effective to be delivered as an augmentation therapy for patients with persistent negative symptoms. The optimal treatment system for this population can be immediately translated to clinical practice and benefit patients in need.

Inclusion Criteria:

1. Age ≥21 and ≤65 years;
2. With primary diagnosis of schizophrenia or schizoaffective disorder;
3. Patients experienced prominent and persistent negative symptoms [Scale for the Assessment of Negative Symptoms (SANS) score ≥3 or Positive and Negative Symptoms Scale (PANSS)- negative subscale score ≥20] in past 6 months;
4. No clinically significant positive symptoms [PANSS positive subscale score <20];
5. No clinically significant depressive symptoms [Calgary Depression Scale for Schizophrenia (CDSS) score subscale <12];
6. Able to give consent.

Exclusion Criteria:

1. With current misuse of or dependence on illegal drugs or alcohol;
2. High Suicide risk;
3. History of epileptic seizures;
4. With severe brain trauma, injury or other neurological diseases;
5. Metal (implants) in the skull;
6. Pregnancy

Upon request, as approved by DSRB.