Accelerated Transcranial Magnetic Stimulation for People With Schizophrenia Treated With Clozapine

Accelerated Neuromodulation of Prefrontal Circuitry During Clozapine Treatment

In this study, the investigators will examine whether a type of repetitive transcranial magnetic stimulation called accelerated intermittent theta burst stimulation (iTBS) can augment neurocognition in individuals who receive treatment with clozapine. Following a baseline evaluation and magnetic resonance imaging (MRI), participants will undergo a session of iTBS +MRI and session of sham delivery + MRI. The order for these sessions will be blinded and randomized. The investigators predict that accelerated iTBS will enhance neurocognition relative to sham delivery.

Inclusion Criteria:

1. A current Diagnostic and Statistical Manual of Mental Disorders 5 (DSM 5)-defined diagnosis of schizophrenia or schizoaffective disorder
2. age 18-65 years
3. at least 4 months of clozapine treatment
4. history of at least 2 failed antipsychotic trials
5. competency and willingness to sign informed consent
6. A clinically optimized dosage of clozapine, unchanged for at least 1 month, with a minimum of 150 mg/day

Exclusion Criteria:

1. Serious neurologic or medical condition/treatment that impacts the brain
2. a significant risk of suicidal or homicidal behavior
3. cognitive or language limitations, or any other factor that would preclude subjects providing informed consent
4. pregnancy or postpartum (<6 weeks after delivery or miscarriage)
5. history of treatment with electroconvulsive therapy
6. contraindications for magnetic resonance imaging (e.g., a pacemaker)
7. Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders 5 (DSM 5)-verified moderate or severe substance use disorder, including alcohol use disorder
8. seizure disorder or prior history of seizures on clozapine
9. patients taking both bupropion and clozapine
10. prior issues with intermittent theta burst stimulation/transcranial magnetic stimulation administration

Concomitant treatment with serotonin and norepinephrine reuptake inhibitors will be examined on a case-by-case basis.