The Great American Clozapine Initiative

The Angry Moms National Clozapine Modernization Initiative:

A Roadmap for Modernizing Clozapine Policy, Access, and Clinical Practice in the United States

Response to the U.S. Department of Health and Human Services RFI:

Making America Healthy Again: Chronic Disease Prevention and Treatment

Prepared by: The Angry Moms, July 2026

Great American Recovery - The Angry Moms National Clozapine Modernization Initiative.pdf

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The Angry Moms is a national grassroots organization of mothers, families, caregivers, patients, and clinicians dedicated to improving access to clozapine and other evidence-based treatment. We participated in the November 2024 FDA advisory committee meeting that contributed to the elimination of the Clozapine REMS program and respectfully submit the following recommendations to modernize clozapine policy in the United States.

1. Modernize national clozapine treatment guidelines.

2. Recognize clozapine's role in substance use recovery.

3. Eliminate "Shadow REMS" programs.

4. Modernize FDA prescribing information.

5. Modernize hematologic monitoring.

6. Expand access to finger-stick and point-of-care ANC testing.

7. Modernize the clozapine workforce and clinical education.

8. Prevent avoidable treatment interruptions.

9. Expand FDA indications.

10. Modernize available tablet strengths.

11. Improve access to GLP-1 therapy.

12. Develop a National Clozapine Action Plan.

13. Launch a National Clozapine Public Awareness Campaign.

14. Establish a National Pediatric Clozapine Initiative.

15. Validate pediatric finger-stick ANC testing.

16. Fund biomarker research for precision clozapine care.

17. Protect continuity through an emergency clozapine supply.

18. Protect the right to access clozapine.

19. Establish a National Clozapine Report Card.

20. Create a National Network of Clozapine Centers of Excellence.

    
    

Collectively, these recommendations provide a roadmap for improving patient safety and expanding access to the most effective treatment for schizophrenia.

Expanded Details and Supporting Evidence for The Angry Moms’ Twenty Recommendations to Modernize Clozapine Policy in the United States:

1. Modernize National Treatment Guidelines to Reflect Emerging Evidence Supporting Earlier Clozapine Use

Clozapine is the most effective medication for schizophrenia, yet too many patients spend years cycling through ineffective medications while losing their education, careers, families, housing, and sometimes their lives before clozapine is ever offered. National treatment guidelines should encourage earlier, individualized, evidence-based use of clozapine, including consideration as a second-line treatment for appropriate patients. We are especially concerned that clozapine's FDA-approved suicide indication has become "the forgotten indication." Too many clinicians mistakenly believe patients must first prove treatment resistance before clozapine can be prescribed for recurrent suicidal behavior. They do not. For individuals with schizophrenia or schizoaffective disorder who present with recurrent suicidal behavior, clozapine should be considered a first-line treatment option based on its unique FDA-approved indication. HHS should modernize national treatment guidelines and encourage the FDA and professional organizations to prominently feature the suicide indication, including consideration of listing it before treatment-resistant schizophrenia in prescribing information and educational materials.

Supporting Evidence: InterSePT (Meltzer et al., 2003) established clozapine as the only antipsychotic approved to reduce recurrent suicidal behavior in schizophrenia and schizoaffective disorder. The CATIE trial (Lieberman et al., 2005) demonstrated clozapine's superior effectiveness among patients who discontinued a previous antipsychotic because of inadequate efficacy, reinforcing its role as the most effective treatment for schizophrenia. Taipale et al. (2025) demonstrated superior outcomes when patients were switched to clozapine after their first relapse, challenging the longstanding third-line treatment paradigm. Okhuijsen-Pfeifer et al. (2018) concluded that earlier use of clozapine may improve outcomes in appropriate patients. de Leon (2025) estimated that increasing clozapine prescribing to just 10% of people with schizophrenia could prevent hundreds of thousands of suicide deaths worldwide while highlighting that the public health cost of underprescribing far exceeds the mortality from agranulocytosis. Zarzar described clozapine's anti-suicidal indication as "the forgotten indication," and Kelly (NAMICon 2026) emphasized that recurrent suicidal behavior is an independent FDA-approved indication that should prompt first-line consideration of clozapine rather than waiting for treatment resistance.

2. Recognize Clozapine's Role in Recovery from Co-Occurring Substance Use Disorders

Emerging evidence suggests clozapine may represent one of the most effective treatments available for co-occurring schizophrenia and substance use disorders, particularly cannabis use disorder. Observational studies, systematic reviews, registry studies, and real-world specialty practices consistently demonstrate substantial reductions in cannabis use, alcohol use, tobacco use, relapse, and hospitalization after clozapine initiation. These findings warrant a federally funded multicenter trial evaluating clozapine as a treatment for psychosis with co-occurring substance use disorders and consideration of expanded FDA indications if confirmed.

Supporting Evidence: Green et al. first demonstrated reduced substance use with clozapine compared with other antipsychotics. Brunette et al. and Rafizadeh et al. reported consistent reductions in alcohol, cannabis, and other substance use among individuals treated with clozapine. de Leon (2025) identified reduced substance use as one of clozapine's major public health benefits. Laitman (2022) reported that the Team Daniel cohort, a real-world cohort of more than 120 patients treated with a clozapine-centered approach, achieved an 82% recovery rate from substance use disorders after one year, including an 82% recovery rate from cannabis use disorder. These promising findings highlight the need for large prospective validation studies.

3. Eliminate “Shadow REMS” Programs That Continue to Restrict Access

The FDA eliminated the Clozapine REMS because the program had become a barrier to treatment access, but many patients are still living under REMS-like local rules. During the FDA advisory process, patients, caregivers, psychiatrists, pharmacists, APA, NAMI, and advocacy groups described dangerous interruptions caused by rigid monitoring and dispensing requirements. Now, some hospitals, clinics, pharmacies, and health systems continue to operate “Shadow REMS” programs: 7- or 14-day medication supplies, prescriptions held until ANC results are reviewed, repeated visits for blood draws and medication pickup, and treatment interruptions caused by transportation failures, lab delays, staffing problems, or liability fears rather than medical necessity. HHS should issue national guidance discouraging local policies that recreate REMS beyond current FDA recommendations and should make clear that clozapine continuity is a patient-safety priority.

Supporting Evidence: FDA (2025) eliminated the Clozapine REMS after determining it was no longer necessary to ensure safe use and had become a barrier to access. Richmond (2026) documented that one year later, some clinics still required twice-weekly visits, delayed dispensing until ANC results were reviewed, and issued only seven-day supplies, contributing to clozapine discontinuation and catastrophic relapse. Meyer & Rubio (2025) emphasized that clinicians must weigh the small long-term risk of severe neutropenia against the serious risk of clozapine interruption and should use shared decision-making when monitoring barriers threaten continuation. de Leon et al. (2026) reported that suicide risk increases sharply after clozapine discontinuation and emphasized avoiding nonadherence and treatment interruption, especially in high-risk patients. The Angry Moms (2024) documented patient and caregiver reports of “no blood, no drug” policies, medication rationing, delayed refills, and preventable interruptions before REMS ended.

4. Modernize FDA Prescribing Information to Support Precision Dosing and Safer Clozapine Initiation

Clozapine prescribing information should be modernized to reflect current scientific understanding of individualized dosing and adverse-effect prevention. The existing label continues to promote standardized titration schedules that may be too aggressive for many patients, particularly poor metabolizers and individuals of Asian or Indigenous American ancestry, while providing limited guidance regarding serum clozapine concentrations, smoking status, C-reactive protein (CRP) and other indicators of inflammation, CYP1A2 drug interactions, temporary dose reductions during infection or pneumonia, and safe cross-titration from previous antipsychotics. Too many patients are incorrectly labeled "clozapine intolerant" after experiencing preventable adverse effects caused by overly rapid titration rather than the medication itself. HHS should encourage the FDA and professional organizations to update prescribing information and national treatment guidelines to support precision medicine, including individualized titration, therapeutic drug monitoring, appropriate use of inflammatory biomarkers such as CRP, proactive management of common adverse effects, and evidence-based strategies that improve both safety and long-term treatment success.

Supporting Evidence: de Leon et al. (2020, 2025) proposed precision dosing strategies based on ancestry, smoking status, inflammatory biomarkers including CRP, serum clozapine concentrations, and metabolizer status, demonstrating that optimal maintenance doses may vary several-fold between patients and that slower, individualized titration can reduce inflammatory complications. An international Delphi consensus panel (Siskind et al., 2025) recommended substantially slower titration to reduce myocarditis risk while emphasizing individualized dosing and monitoring. Meyer & Rubio (2025) supported therapeutic drug monitoring, shared decision-making, and individualized dosing strategies in the post-REMS era. Laitman et al. (2026) described the Team Daniel approach, in which ultra-slow titration combined with aggressive side-effect management was associated with high rates of long-term recovery and treatment success.

5. Modernize Hematologic Monitoring to Preserve Safe Access to Clozapine

National clozapine monitoring recommendations should be modernized to reflect current evidence while ensuring that laboratory testing never becomes an unnecessary barrier to treatment. HHS should encourage the FDA and professional organizations to support flexible, individualized ANC monitoring based on time on therapy, patient risk factors, and clinical judgment. When standard laboratory testing remains impossible despite reasonable accommodations, clinicians should retain the ability to continue clozapine using informed consent, shared decision-making, individualized slow titration, routine vital signs, and careful monitoring for symptoms of neutropenia and other serious adverse effects when the risks of untreated schizophrenia outweigh the risks of continued treatment. Schizophrenia is a life-threatening illness. Every reasonable effort should be made to obtain laboratory monitoring. However, when every available option has been exhausted, the inability to obtain a blood sample should not automatically deny patients access to the most effective treatment available.

Supporting Evidence: FDA (2025) eliminated the Clozapine REMS after concluding that the program had become a barrier to treatment access while continuing to recommend ANC monitoring through the prescribing information. Siskind et al. (2025) developed international Delphi consensus guidelines recommending substantially reduced ANC monitoring after the initial treatment period, individualized risk-based monitoring, and greater emphasis on clinically meaningful adverse effects beyond neutropenia. Meyer & Rubio (2025) emphasized that clinicians should weigh the risks of clozapine discontinuation against the now very low long-term risk of severe neutropenia and supported individualized monitoring through shared decision-making. de Leon (2025) argued that the public health consequences of underprescribing and unnecessarily interrupting clozapine far exceed the mortality associated with agranulocytosis, estimating that substantially broader clozapine use could prevent hundreds of thousands of premature deaths worldwide. de Leon et al. (2026) further highlighted the marked increase in suicide risk following clozapine discontinuation and emphasized that maintaining continuity of treatment is a critical patient safety priority.

6. Expand Access to Finger-Stick and Point-of-Care ANC Testing

FDA-cleared finger-stick and other point-of-care ANC technologies should become a routine option for patients receiving clozapine. These technologies dramatically reduce the burden of repeated venous blood draws, improve treatment adherence, expand access in rural and underserved communities, and provide a reasonable accommodation for patients with autism, intellectual disability, severe anxiety, poor venous access, transportation barriers, or other conditions that make traditional laboratory testing difficult. Finger-stick testing also allows patients with low or borderline ANC values to be monitored more frequently when clinically appropriate, reducing unnecessary treatment interruptions and preventing avoidable clozapine discontinuation.

Federal policy should recognize point-of-care ANC testing as an essential component of equitable access to clozapine. Patients should not be forced to pay thousands of dollars out of pocket for technology that preserves access to a lifesaving medication, and clinics need clear reimbursement and billing pathways to support its routine use. Medicare, Medicaid, and commercial insurers routinely cover home glucose monitoring for diabetes and point-of-care coagulation monitoring (e.g., INR) because these technologies improve safety, access, and long-term outcomes. Individuals treated with clozapine deserve the same commitment to monitoring access and reasonable accommodation. The annual cost of clozapine, ANC monitoring, and point-of-care testing is substantially lower than many long-acting injectable antipsychotics and patented oral psychiatric medications while offering the greatest clinical benefit for many patients.

Supporting Evidence: Whiston et al. demonstrated that finger-stick point-of-care ANC testing provides accurate and reliable monitoring while substantially reducing the burden of venous blood draws for patients receiving clozapine. Kelly et al. showed that point-of-care ANC testing is feasible, acceptable to patients and clinicians, and has the potential to improve clozapine initiation, adherence, and continuity of care. FDA (2026) subsequently granted CLIA waiver for point-of-care finger-stick WBC/ANC testing, recognizing its suitability for routine clinical use. Richmond (2026) identified finger-stick testing as one of the most promising solutions for improving clozapine access in the post-REMS era while highlighting persistent reimbursement barriers. The international Delphi consensus (Siskind et al., 2025) further supported individualized monitoring strategies that reduce unnecessary barriers while preserving patient safety.

7. Modernize the National Clozapine Workforce and Clinical Education

The United States must rebuild clozapine competency across the entire healthcare workforce. For decades, clinicians have been taught that clozapine is a dangerous “last resort” medication, and that outdated message is still being taught in health professional programs today. The science changed. The FDA changed. REMS changed. Much of the education did not. HHS should fund a national clozapine education initiative across medical, nursing, psychiatric NP, PA, pharmacy, emergency medicine, hospital medicine, correctional health, and primary care training. Every clinician caring for people with schizophrenia should understand clozapine initiation, continuation, monitoring, side-effect management, treatment interruptions, and the risks of not using clozapine.

Supporting Evidence: Zarzar (2024) argued that clozapine proficiency should become a formal milestone in psychiatric training. Brito Castro et al. (2026) reviewed “clozaphobia” as a driver of clozapine underprescription, including clinician fear, misinformation, and overestimation of risks. Puzantian et al. (2019) identified lack of prescriber knowledge, lack of confidence, negative attitudes, administrative barriers, formulary limitations, and weak health-system infrastructure as major barriers to clozapine use. Leung & Cotes (2025) called for a national effort to increase clozapine use in the post-REMS era through improved clinician education, implementation support, and modernized prescribing practices. de Leon (2025) identified “clozaphobia” as a major contributor to worldwide clozapine underuse and emphasized the need for a massive educational effort.

8. Prevent Avoidable Clozapine Treatment Interruptions Through National Continuity Standards

Abrupt interruption of clozapine is a medical emergency—not merely a missed medication dose. Published literature describes cholinergic rebound, severe rebound psychosis, delirium, catatonia, autonomic instability, dopamine supersensitivity phenomena, increased suicide risk, and, in some patients, failure to fully regain the remarkable response they previously achieved with clozapine. These complications are largely preventable.

Unfortunately, avoidable interruptions remain commonplace. Clozapine is routinely withheld during emergency department visits, psychiatric hospitalizations, medical admissions, jail intake, prison transfers, pharmacy delays, insurance changes, and unnecessary "Shadow REMS" policies. No other medication capable of producing such serious withdrawal consequences would be managed this way.

We urge HHS to establish national clozapine continuity standards comparable to those used for insulin, anticonvulsants, transplant medications, and other medically critical therapies. Every hospital, emergency department, psychiatric facility, correctional facility, pharmacy, and behavioral health agency that serves individuals with schizophrenia should maintain a written Clozapine Continuity Plan subject to oversight by licensing and accrediting organizations. These plans should ensure uninterrupted access whenever medically appropriate, including during admissions, transfers, discharge, and temporary disruptions in laboratory testing.

Supporting Evidence: Blackman et al. (2022) comprehensively reviewed clozapine withdrawal syndromes, including cholinergic rebound, rebound psychosis, delirium, catatonia, autonomic instability, and relapse, and recommended avoiding abrupt discontinuation whenever possible. de Leon et al. described clozapine as the antipsychotic most consistently associated with clinically significant withdrawal syndromes. Chouinard et al. (2017) described dopamine supersensitivity psychosis following antipsychotic withdrawal.

9. Expand Clozapine Indications for Aggression and Other Severe Neuropsychiatric Conditions

HHS should direct FDA, NIMH, SAMHSA, and other federal partners to evaluate expanded clozapine indications for serious neuropsychiatric conditions where evidence already exists but no pharmaceutical sponsor has a financial incentive to act. The strongest immediate candidate is reduction of recurrent aggression and violence in serious mental illness. Clozapine’s anti-aggressive effects are recognized in major guidelines and supported by systematic reviews, yet the FDA label still fails to reflect this lifesaving benefit. Additional federal review should also examine treatment-resistant bipolar disorder and psychosis in Parkinson’s disease, where clozapine has evidence but limited commercial pathway. Patented drugs routinely receive new indications because companies fund the trials. Clozapine is generic, inexpensive, and uniquely effective, so expanded indications will require government-funded evidence review, trials, and regulatory action.

Supporting Evidence: Honigfeld (2025) petitioned FDA to add an indication for reducing recurrent aggressive behavior in serious mental illness, citing APA guidelines, TRRIP consensus, and systematic reviews supporting clozapine’s unmatched anti-aggressive effects. Frogley et al. (2012) and Faden & Citrome (2024) found substantial evidence supporting clozapine for persistent aggression and violence in schizophrenia and schizoaffective disorder. Li et al. (2015) reviewed evidence supporting clozapine in treatment-resistant bipolar disorder. Srisurapanont et al. (2024) found that clozapine was the most effective second-generation antipsychotic for Parkinson's disease psychosis, with minimal worsening of motor symptoms and high overall acceptability.

10. Modernize Available Clozapine Tablet Strengths

FDA and HHS should support development of higher-strength clozapine tablets to reduce pill burden for patients who require moderate or high daily doses. Large pill burdens make adherence harder, complicate medication administration in hospitals and correctional settings, increase dispensing complexity, and create unnecessary opportunities for missed doses or medication errors. Because clozapine is generic, this modernization may require federal encouragement, regulatory facilitation, or public-private partnership.

Supporting Evidence: Brito Castro et al. (2026) argued that, following the end of the Clozapine REMS, manufacturers should develop higher-strength clozapine tablets and long-acting injectable clozapine. The authors note that a single 400 mg tablet could replace four 100 mg tablets, reducing pill burden and potentially improving adherence in patients with severe psychotic illness.

11. Improve Access to GLP-1 Therapy for Clozapine-Associated Metabolic Disease

HHS should expand access to GLP-1 therapy for patients experiencing clozapine-associated weight gain and metabolic disease. Patients should not have to become diabetic before receiving effective treatment. Preventing obesity, diabetes, cardiovascular disease, kidney disease, disability, and premature mortality is better medicine and better fiscal policy than paying for decades of preventable comorbidity.

Supporting Evidence: Varshney et al. (2025) reviewed 14 studies, including randomized trials, and found that GLP-1 receptor agonists used in patients taking clozapine or olanzapine were consistently associated with lower weight gain and improvements in fasting glucose and HbA1c, with minimal reported psychological, cardiac, or other serious side effects. Larsen et al. (2017, JAMA Psychiatry) demonstrated in a randomized clinical trial that liraglutide improved body weight and glucose metabolism in patients with schizophrenia spectrum disorders treated with clozapine or olanzapine. Lim et al. (2025) reported that tirzepatide fully reversed severe clozapine-induced weight gain in one patient, while insurance-related discontinuation caused rapid weight regain, illustrating why reliable coverage matters.

12. Develop a National Clozapine Action Plan to Double Use in 5 Years

HHS should develop a five-year National Clozapine Action Plan to double appropriate clozapine use in the United States. The plan should coordinate federal efforts to modernize treatment guidelines, improve workforce competency, expand access to point-of-care testing, support continuity of care, reduce unnecessary barriers, fund priority research, and establish national performance measures.

Supporting Evidence: Despite decades of evidence demonstrating clozapine's superiority for treatment-resistant schizophrenia and suicide prevention, the United States has no coordinated national strategy to improve access. The end of the Clozapine REMS removed one federal barrier, but meaningful improvement now requires coordinated leadership across HHS, FDA, SAMHSA, CMS, NIH, professional organizations, and state Medicaid agencies.

13. Launch a National Clozapine Public Awareness Campaign

HHS should support a national public awareness campaign to reduce "clozaphobia" among patients, families, clinicians, and policymakers. Television commercials, social media campaigns, online videos, banner advertisements, and other public education efforts have made newer branded antipsychotics such as Cobenfy and Caplyta widely recognized by both patients and prescribers, while clozapine, the most effective medication for schizophrenia, remains largely unknown, misunderstood, and stigmatized. Clozapine deserves the same level of evidence-based public education emphasizing its effectiveness, FDA-approved suicide indication, modern monitoring options, and life-saving potential.

Supporting Evidence: Direct-to-consumer television and digital advertising has substantially increased awareness of newer branded antipsychotics, while generic clozapine receives virtually no public education because no manufacturer has a financial incentive to promote it. FDA has issued an untitled letter regarding misleading claims in a Cobenfy television advertisement, highlighting the importance of balanced, evidence-based public education. A federally supported clozapine awareness campaign could provide accurate information to both patients and clinicians, encourage appropriate prescribing, and improve access to the most effective treatment for schizophrenia.

14. Establish a National Pediatric Clozapine Initiative

HHS should fund a Pediatric Clozapine Initiative to support multicenter studies, pediatric labeling, clinical guidance, and workforce training for children and adolescents with severe treatment-resistant psychosis, recurrent suicidal behavior, and severe treatment-resistant aggression, including in autism and intellectual disability. Newer branded antipsychotics such as Vraylar have recently obtained pediatric indications, while clozapine, the gold-standard medication for treatment-resistant schizophrenia, still lacks adequate pediatric labeling, guidance, and access. Children with the most severe illness should not be denied the most effective treatment simply because clozapine is generic and lacks a commercial sponsor.

Supporting Evidence: FDA recently expanded pediatric indications for Vraylar, demonstrating that antipsychotic labeling continues to evolve as new evidence emerges. Adnan et al. (2022) concluded in a systematic review and meta-analysis that clozapine is a safe and effective treatment for childhood- and adolescent-onset schizophrenia and called for larger multicenter trials and updated clinical guidance. Schneider et al. (2014) concluded in a systematic review that clozapine is an effective and generally well-tolerated treatment for early-onset schizophrenia, while Schneider et al. (2015) reported favorable long-term treatment persistence and functional outcomes in a nationwide population-based study of youth treated with clozapine. Kumra et al. (1996, 2008), Shaw et al. (2006), and Sporn et al. (2007) demonstrated superior efficacy compared with other antipsychotics in treatment-resistant childhood-onset schizophrenia. Chalasani et al. (2001) and Kranzler et al. (2008) reported significant improvements in psychotic symptoms, aggression, and overall clinical outcomes among youth with treatment-resistant schizophrenia. Additional studies support further investigation of clozapine for severe aggression associated with autism spectrum disorder and intellectual disability.

15. Validate Pediatric Finger-Stick ANC Testing

HHS and FDA should fund pediatric validation studies for finger-stick ANC testing to expand evidence, regulatory support, and clinical adoption in children and adolescents receiving clozapine. Although finger-stick devices are already being used off-label in some pediatric settings, there is currently no FDA-cleared and CLIA-waived indication specifically for patients under 21. Pediatric validation would increase confidence, accelerate adoption, and improve access to clozapine monitoring, particularly in inpatient, residential, and other congregate care settings.

Supporting Evidence: FDA 510(k) K243348 cleared Athelas Home for quantitative WBC and neutrophil percentage testing using capillary finger-stick blood for patient self-testing and point-of-care settings. Whiston et al. (2025) reviewed point-of-care clozapine testing and concluded that capillary POCT devices can reduce venous blood draw burden, improve clozapine utilization and adherence, and provide acceptable accuracy, while also emphasizing the need for additional research in diverse patient populations, including varied ages.

16. Fund Biomarker Research for Precision Clozapine Care

HHS, FDA, and NIMH should fund research into HLA, Duffy antigen status, pharmacogenomics, inflammatory markers, and other biomarkers that may predict clozapine-associated neutropenia, agranulocytosis, myocarditis, toxicity, and safe long-term monitoring intervals. Better risk prediction could reduce unnecessary fear, personalize monitoring, prevent serious adverse events, and expand access to clozapine for patients who need it.

Supporting Evidence: Taylor et al. (2022) demonstrated that true clozapine-induced life-threatening agranulocytosis follows a distinctive rapid neutrophil decline pattern and recommended future genetic studies distinguish true agranulocytosis from benign or threshold-defined neutropenia. Pharmacogenomic studies have identified associations with HLA-DQB1, HLA-B, and related genetic variants. Kelly and colleagues' NIMH-funded research has investigated the Duffy (ACKR1/DARC) genotype and Benign Ethnic Neutropenia (BEN) as biomarkers to safely expand clozapine access.

17. Protect Continuity Through an Emergency Clozapine Supply

HHS should establish a national recommendation supporting an emergency clozapine supply, such as up to 14 days when clinically appropriate, to prevent avoidable treatment interruption while urgent clinical, pharmacy, laboratory, transportation, insurance, disaster, or care-transition issues are resolved. Clozapine should be treated like other medically critical therapies where short-term continuity planning is a patient-safety priority.

Supporting Evidence: CDC emergency preparedness guidance recommends maintaining a 7–10 day supply of prescription medications, and FEMA advises patients to plan for emergency access to medications and supplies. Clozapine discontinuation is associated with rebound psychosis, cholinergic rebound, delirium, catatonia, suicide risk, and avoidable relapse. Blackman et al. (2022), de Leon et al. (2020), and de Leon et al. (2026) support avoiding abrupt clozapine discontinuation whenever possible. National guidance supporting a limited emergency supply would help prevent avoidable interruptions during temporary access barriers.

18. Protect the Right to Access Clozapine

HHS should issue federal guidance recognizing access to clozapine as a patient-safety right when clinically appropriate. Patients should not be denied, delayed, interrupted, or rationed clozapine because of avoidable administrative barriers, rigid local monitoring rules, pharmacy delays, liability fears, or lack of reasonable monitoring accommodations. Guidance should also support appropriate clinician liability protections when providers use informed consent, shared decision-making, clinical judgment, and reasonable monitoring efforts to preserve access to clozapine.

Supporting Evidence: Arizona Senate Bill 1716 (2026) provides a model by prohibiting insurers, Medicaid contractors, jails, and prisons from denying, discontinuing, interrupting, delaying, or rationing clozapine when medically appropriate, while allowing modified or alternative hematologic monitoring under informed consent and clinical judgment. Brito Castro et al. (2026) described clinician fear of adverse events, legal liability, and “clozaphobia” as major contributors to clozapine underprescribing. Meyer & Rubio (2025) and de Leon et al. (2026) emphasize that clinicians must weigh rare serious adverse events against the substantial risks of clozapine discontinuation, relapse, suicide, and untreated schizophrenia. 

19. Establish a National Clozapine Report Card

HHS should establish a National Clozapine Report Card with annual public reporting of national clozapine quality measures. Just as diabetes, hypertension, cardiovascular disease, cancer screening, and other chronic illnesses are tracked using standardized quality measures and report cards, schizophrenia should receive the same commitment to measurement, transparency, accountability, and continuous quality improvement. Because clozapine is the only FDA-approved medication to reduce recurrent suicidal behavior in schizophrenia and schizoaffective disorder, national suicide prevention efforts should also include measurement of appropriate clozapine access and utilization among eligible patients.

Supporting Evidence: CMS, NCQA, CDC, and state Medicaid programs routinely use standardized quality measures and public reporting to improve outcomes for chronic diseases and to monitor national health priorities, including suicide prevention. A National Clozapine Report Card should include measures such as clozapine utilization among eligible patients with schizophrenia, appropriate use for patients with recurrent suicidal behavior, time to clozapine initiation, treatment interruption rates, continuity of care following hospitalization or incarceration, racial and geographic disparities, pediatric utilization, point-of-care testing adoption, hospitalization rates, suicide, mortality, and state-by-state performance. Annual reporting would benchmark progress, identify disparities, and measure the success of national clozapine modernization efforts.

20. Create a National Network of Clozapine Centers of Excellence

HHS should establish a national network of Clozapine Centers of Excellence to serve as regional referral, consultation, education, and implementation hubs. These centers would provide expert consultation for complex cases, clinician education, tele-mentoring, inpatient and outpatient implementation support, point-of-care testing expertise, research collaboration, and technical assistance to community providers. Similar to cancer centers, stroke centers, and Alzheimer's Disease Research Centers, Clozapine Centers of Excellence would ensure that every clinician has access to expert guidance regardless of geographic location. These centers could also serve as regional leaders for clinician education, pediatric consultation, biomarker research, quality improvement, and implementation of the National Clozapine Action Plan.

Supporting Evidence: The Maryland Clozapine CHAMPION-ECHO program, led by Dr. Deanna Kelly and colleagues, demonstrated that a statewide Project ECHO model can improve clinician knowledge, confidence, and competence in clozapine prescribing through expert tele-mentoring, case consultation, and implementation support. The CHAMPION program also integrated a statewide consultation service and point-of-care ANC testing to reduce barriers to treatment. Expanding this model into a national network of regional Clozapine Centers of Excellence would provide sustainable infrastructure for education, consultation, quality improvement, research, and implementation across the United States.

Conclusion:

The Angry Moms welcomes the opportunity to work collaboratively with HHS, FDA, SAMHSA, CMS, NIH, professional organizations, researchers, clinicians, patients, and caregivers to advance these recommendations and improve access to evidence-based clozapine treatment nationwide.

References

Government Documents and Guidance

Arizona Legislature. (2026). SB1716: Clozapine access, continuity of care, and informed consent.

Arizona Legislature. (2025). SB1720: Clozapine access and provider training.

Centers for Disease Control and Prevention. Emergency preparedness: Maintaining prescription medications during disasters.

Federal Emergency Management Agency. Emergency medication preparedness guidance.

U.S. Food and Drug Administration. (2003). Clozaril (clozapine) prescribing information.

U.S. Food and Drug Administration. (2025). Elimination of the Clozapine Risk Evaluation and Mitigation Strategy (REMS).

U.S. Food and Drug Administration. (2025). Untitled Letter regarding Cobenfy direct-to-consumer television advertising.

U.S. Food and Drug Administration. (2026). 510(k) Clearance K243348: Athelas Home WBC/ANC System.

U.S. Food and Drug Administration. (2026). CLIA Waiver for Athelas Point-of-Care WBC/ANC Testing.

Honigfeld G. (2025). Citizen Petition to Expand FDA Indications for Clozapine for Aggression.

Peer-Reviewed Literature

Adnan M, et al. Clozapine for childhood- and adolescent-onset schizophrenia: A systematic review and meta-analysis. Psychiatry Res. 2022.

Blackman G, et al. Reducing the risk of withdrawal symptoms and relapse following clozapine discontinuation—Is it feasible to develop evidence-based guidelines? Schizophr Bull. 2022;48(1):176-189.

Brito Castro J, et al. Underprescription of clozapine: A narrative review regarding clozaphobia. Hum Psychopharmacol. 2026.

Brunette MF, et al. Clozapine use and relapses of substance use disorder among patients with co-occurring schizophrenia and substance use disorders. Schizophr Bull. 2006;32(4):637-643.

Butler E, et al. Should clozapine be offered as a second-line antipsychotic? Lancet Psychiatry. 2025;12(2):85-86.

Chalasani L, et al. Clozapine impact on clinical outcomes and aggression in severely ill adolescents with childhood-onset schizophrenia. Can J Psychiatry. 2001;46(10):965-968.

Chouinard G, et al. Antipsychotic-Induced Dopamine Supersensitivity Psychosis: Pharmacology, Criteria, and Therapy. Psychother Psychosom. 2017;86(4):189–219.

de Leon J. Prescribing clozapine to 10% of patients with schizophrenia may save 320,000 lives and cost 2,400 deaths from agranulocytosis. Eur Neuropsychopharmacol. 2025;98:58-61.

de Leon J, et al. Clozapine and suicide in VigiBase: Most important fatal outcome in young males and differences between attempted and completed suicide. J Clin Psychopharmacol. 2026.

de Leon J, et al. A rational use of clozapine based on adverse drug reactions, pharmacokinetics, and clinical pharmacopsychology. Psychother Psychosom. 2020;89(4):200-214.

Faden J, Citrome L. A systematic review of clozapine for aggression and violence in patients with schizophrenia or schizoaffective disorder. Schizophr Res. 2024.

Frogley C, et al. A systematic review of the evidence of clozapine's anti-aggressive effects. Int J Neuropsychopharmacol. 2012;15(9):1351-1371.

Green AI, et al. The effects of clozapine on alcohol and drug use disorders among patients with schizophrenia. Schizophr Bull. 2000.

Kelly DL, et al. Feasibility and patient-reported satisfaction using a novel point-of-care fingerstick method for monitoring absolute neutrophil count for clozapine. Ann Clin Psychiatry. 2021;33(2):116-123.

Kelly DL, et al. FDA eliminates the Clozapine REMS—What comes next? JAMA Psychiatry. 2025.

Kranzler H, et al. Clozapine: Its impact on aggressive behavior among children and adolescents with schizophrenia. J Am Acad Child Adolesc Psychiatry. 2005;44(1):55-63.

Kumra S, et al. Childhood-onset schizophrenia: A double-blind clozapine-haloperidol comparison. Arch Gen Psychiatry. 1996;53(12):1090-1097.

Kumra S, et al. Clozapine and high-dose olanzapine in refractory early-onset schizophrenia: A 12-week randomized, double-blind comparison. J Child Adolesc Psychopharmacol. 2008;18(4):307-316.

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News and Other Sources

Markovich A. (2026). Arizona Center for Investigative Reporting. Treatment Interrupted

Ault A. (2025) Medscape. FDA Ended Clozapine REMS. But Will It Increase Prescribing?

Richmond L. (2026). Psychiatric News. One Year Later: The End of the Clozapine REMS

The Angry Moms. (2024). Patient and caregiver reports submitted during the FDA REMS review.

The Angry Moms. (2024). Interview with Dr. Ted Zarzar (https://www.theangrymoms.com/post/can-the-fda-be-trusted-with-clozapine)