Consultation clinic provides evaluation and education for patients who may benefit from clozapine

Clozapine is the treatment of choice for treatment-resistant schizophrenia, and yet it is highly underutilized in the United States. It is estimated that up to 30% of patients with schizophrenia do not respond to first-line antipsychotic medications and are thus considered treatment resistant. Clozapine has been shown to be more effective for treatment-resistant schizophrenia than other antipsychotics, with benefits including reduction in positive symptoms, negative symptoms and functional impairment, as well as improvement in quality-of-life ratings.

Despite these benefits, clozapine is estimated to be prescribed to only 4% of patients with schizophrenia nationally, suggesting the vast majority of patients who might benefit from clozapine are not receiving it. Clozapine’s underutilization is likely due to concern about adverse side effects and the burdens imposed by FDA requirements for hematologic monitoring and reporting to a national registry. Despite potential adverse effects, people who take clozapine have been shown to have a lower risk of premature mortality, as compared to patients on other antipsychotics.

Allison Brandt directs the Johns Hopkins Clozapine Consultation Clinic. The clinic is designed to provide an expert opinion about whether clozapine may be appropriate for a patient and, if so, to provide advice and education for patients, family members and clinicians about practical strategies for implementing clozapine treatment.

Who finds the consult clinic most helpful?

We help patients and family members who have questions about whether clozapine may be a beneficial treatment for them, or who have concerns about the potential risks and want to learn more. We work with psychiatric providers who may be unfamiliar with prescribing clozapine and would benefit from support in initiating it, including regulatory and clinical issues, and in managing adverse effects. We also see patients who have previously taken clozapine and experienced side effects. We work with these patients and their clinicians on when and how to safely reinitiate clozapine.

What are the best practices for hematologic monitoring in clozapine use?

A rare adverse effect of clozapine is agranulocytosis, the loss of production of neutrophils, an essential white blood cell for combating infections. Because of this potential side effect, the FDA requires all patients taking clozapine to undergo weekly monitoring of absolute neutrophil count for the first six months, followed by biweekly monitoring for months six to 12, and monthly monitoring thereafter. Ongoing research at Johns Hopkins, as well as a recently published study from Australia, suggests that the risk of clinically relevant neutropenia is low (less than 1%), and the risk is minimal after three months. Given this low risk, there are ongoing advocacy efforts to encourage the FDA to revise the current ANC monitoring requirement.

What are other potential adverse effects of clozapine?

Clozapine can have significant benefits for people with treatment-resistant schizophrenia. This must be weighed against a number of potential risks. In addition to neutropenia, clozapine has a number of both serious and non-serious side effects. These include seizures, myocarditis, severe constipation, orthostatic hypotension, drooling, sedation and weight gain. With proper dosing, monitoring and interventions, the risk or inconvenience of these side effects can be markedly reduced. The Johns Hopkins Clozapine Consultation Clinic provides patients and their clinicians advice on managing potential side effects.

References: 

Gurrera RJ, Gearin PF, Love J, et al. Recognition and management of clozapine adverse effects: A systematic review and qualitative synthesis. Acta Psychiatrica Scandinavica. 2022;145(5):423-441. doi:10.1111/acps.13406

Leung JG, de Leon J, Frye MA, Singh B, Cotes RO, McElroy SL. The Modernization of Clozapine: A Recapitulation of the Past in the United States and the View Forward. Journal of Clinical Psychopharmacology. 2022;42(6):565. doi:10.1097/JCP.0000000000001606

Northwood K, Myles N, Clark SR, et al. Evaluating the epidemiology of clozapine-associated neutropenia among people on clozapine across Australia and Aotearoa New Zealand: a retrospective cohort study. The Lancet Psychiatry. 2024;11(1):27-35. doi:10.1016/S2215-0366(23)00343-7