{"doi":"10.1002/mds.30295","title":"The <scp>FDA</scp> Has Ended Required Blood Monitoring for Clozapine Use—Will This Impact the Management of Parkinson's Disease Psychosis?","abstract":"Clozapine is currently the only effective antipsychotic (AP) for treatment-resistant schizophrenia,1 having been approved for this indication by the Food and Drug Administration (FDA) in 1989. At that time, due to the known risk of developing agranulocytosis (also known as severe neutropenia and typically defined as an absolute neutrophil count [ANC] <500/mm3 or μL), routine white blood cell monitoring was mandated for its use. Initially, the Clozaril Patient Management System (CPMS)2 required indefinite weekly blood draws. However, as evidence emerged showing that the highest risk for neutropenia occurs within the first 3 (84% of agranulocytosis cases) to 6 (96% of cases) months of treatment,1, 3 the requirements evolved. In 2005, the FDA changed the requirements to weekly ANC monitoring for the first 6 months, biweekly from 6 to 12 months, and monthly thereafter. Starting in 2015, CPMS was subsumed under the Risk Evaluation Mitigation Strategy (REMS) Program (https://www.newclozapinerems.com/home#). In February 2025, the FDA lifted the requirement to use the REMS program in conjunction with clozapine prescribing in the United States, aiming to simplify its prescription and increase utilization (https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-clozapine). Although various groups around the world have proposed alternative, less-restrictive hematological monitoring over the years,1 this shift in regulatory requirements introduces uncertainty. Specifically, prescribers are now solely responsible for determining what, if any, hematological monitoring to perform. Further complicating matters, the FDA-approved package insert for clozapine remains unchanged for the time being (https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/019758s106lbl.pdf), continuing to require the monitoring schedule that the REMS program put in place. Additionally, beyond the United States, global guidelines vary considerably with respect to monitoring frequency, discontinuation thresholds, and criteria for rechallenge, with some countries having no monitoring protocols at all.4 The primary rationale behind the stringent blood monitoring protocols is the risk for neutropenia, and subsequently agranulocytosis, associated with clozapine use, with potential for significant morbidity and even mortality. Early data from Europe in the 1970s suggested that up to 2% of patients taking clozapine developed agranulocytosis, contributing to several patient deaths.5 Following clozapine's introduction in the United States, a study was conducted to evaluate clozapine-induced agranulocytosis among 11,555 patients who initiated treatment post-marketing. The cumulative incidence was 0.8% at 12 months, but with very few incident cases after 6 months. Risk of agranulocytosis was independent of dose, although these data were based on patients treated for primary psychiatric disorders (i.e., schizophrenia) at usual doses. Higher age and female sex appeared to have an increased risk.3 A more recent, larger review confirmed the risk of agranulocytosis to be approximately 0.7%, with only 25% of those with mild neutropenia progressing to severe neutropenia.6 About 2% of clozapine-induced agranulocytosis cases were fatal.6 There is mixed evidence regarding whether the risk of developing neutropenia or agranulocytosis is higher for clozapine compared with other APs. Given that an association between clozapine and neutropenia had already been established, this AP has garnered the most attention when it comes to studying agranulocytosis in research and clinical contexts.7, 8 However, a study conducted in Iceland found that patients with schizophrenia being treated with clozapine had an equal risk of developing neutropenia compared with those on other APs.9 A meta-analysis from 2019 did not find a stronger association with clozapine for mild or severe neutropenia compared with risperidone, chlorpromazine, haloperidol, olanzapine, and ","journal":"Movement Disorders","year":2025,"id":570388,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1409869,"name":"Izabelle Schoen","orcid":null,"position":1,"is_corresponding":false},{"id":80309,"name":"Daniel Weintraub","orcid":"0000-0003-0633-7168","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T02:57:07.857542Z","pmid":"40662618","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}