Version July 2025
ANC: absolute neutrophil count; CBC: complete blood count; ECT: electroconvulsive therapy; LAI: long-acting injectable; REMS: Risk Evaluation and Mitigation Strategy; rTMS: repetitive transcranial magnetic stimulation; TRRIP: Treatment Response and Resistance in Psychosis.
* Management of all individuals with schizophrenia is typically multimodal including pharmacologic management and psychosocial interventions. Refer to Inset 1 and UpToDate content for further discussion of the diagnosis and treatment of schizophrenia and treatment-resistant schizophrenia.
¶ Prior to prescribing clozapine, we review potential risks and benefits of clozapine treatment with the patient and family members. Refer to Inset 2 and UpToDate content for discussion of guidelines for prescribing clozapine.
Δ We consider a therapeutic clozapine trial to include at least 24 weeks with a documented plasma level above 350 mg/dL. Refer to UpToDate content for guidelines for prescribing clozapine.
◊ Our preference for ECT augmentation is 2 to 3 ECT treatments weekly for 4 to 6 weeks depending on tolerability and response. Some patients may prefer to not have ECT treatment. In these cases, we move on to the next treatment choice. Refer to UpToDate content for discussion of the use of ECT in psychiatric disorders.
§ We augment clozapine with a nonclozapine antipsychotic (typically aripiprazole) for 12 weeks prior to determining efficacy. Refer to UpToDate content for discussion choice of antipsychotic medication as clozapine augmentation.
¥ Refer to UpToDate content for discussion of monitoring for neutropenia during treatment with clozapine.
‡ Minimal data supports these treatments for resistant schizophrenia. Our preference is a trial of lamotrigine followed by topiramate or minocycline. Neuromodulation is a treatment option when other medication strategies and ECT are not an option or have not been effective.