Overcoming the barriers to identifying and managing treatment-resistant schizophrenia and to improving access to clozapine: A narrative review and recommendation for clinical practice

European Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: 84, P. 35 - 47

Published: April 23, 2024

Clozapine is the only approved antipsychotic for treatment-resistant schizophrenia (TRS). Although a large body of evidence supports its efficacy and favorable risk-benefit ratio in individuals who have failed two or more antipsychotics, clozapine remains underused. However, variations utilization across geographic clinical settings suggest that it could be possible to improve use. In this narrative review expert opinion, we summarized information available literature on mechanisms action, effectiveness, potential adverse events clozapine. We identified barriers leading discouragement prescription internationally, proposed practical solutions overcome each barrier. One main obstacles use lack appropriate training physicians: highlighted need develop specific professional programs train clinicians, both practicing residency, relevance TRS treatment, initiation, maintenance, management events. This approach would facilitate physicians identify eligible patients offer as treatment option early stage disease. also noted increasing awareness benefits among healthcare professionals, people with TRS, their caregivers can help promote Educational material, such leaflets videos, developed distributed achieve goal. The provided article may useful disease burden support patients, navigating complex pathways management.

Language: Английский

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Patterns of C-reactive protein trends during clozapine titration and the onset of clozapine-induced inflammation: a case series of weekly and daily C-reactive protein monitoring

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 21, 2024

Background International guidelines for clozapine titration recommend measuring C-reactive protein (CRP) weekly 4 weeks after initiation to prevent fatal inflammatory adverse events, including myocarditis. However, limited evidence exists regarding whether CRP monitoring can clozapine-induced inflammation. Aims We examined the relationship between trends and development of also explored usefulness limitations during titration. Method This study presents 17 cases daily initiation, respectively. Results Among patients with measurements, 7 had fever. Elevated levels were detected before onset fever in two seven patients. Of five remaining patients, on a previous test been low; however, developed suddenly. 10 no under monitoring, three elevated >3.0 mg/dL. Refraining from increasing dose may have prevented these four became febrile. In both cases, increased almost simultaneously Conclusion Weekly is valuable preventing inflammation, assessing its severity, guiding adjustments. not adequately predict inflammation some cases. Consequently, clinicians should be aware sudden even if are low. Daily better detecting

Language: Английский

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When, Why and How to Re-challenge Clozapine in Schizophrenia Following Myocarditis

CNS Drugs, Journal Year: 2024, Volume and Issue: 38(9), P. 671 - 696

Published: July 1, 2024

Clozapine-induced myocarditis (CIM) is among the most important adverse events limiting use of clozapine as effective treatment for schizophrenia. CIM necessitates immediate termination clozapine, often resulting in its permanent discontinuation with considerable detrimental effects on patients' psychopathology and long-term outcome. Consequently, a re-challenge after increasingly regarded viable alternative, published reports indicating success rate approximately 60%. However, cases re-challenges remain limited. Here, we provide narrative review current state research regarding epidemiology, pathophysiology, risk factors, diagnosis clinical management well synthesis recommendations re-challenging patients CIM. This includes step-by-step guide this crucial procedure based evidence pathophysiology factors Slow dose titration regimes addressing including concomitant valproate olanzapine are both to prevent ensure safe successful re-challenge. Furthermore, discuss utility C-reactive protein, troponin, N-terminal-pro hormone brain natriuretic peptide, therapeutic drug-monitoring cardiac magnetic resonance imaging screening post-CIM re-challenges.

Language: Английский

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Revealing the reporting disparity: VigiBase highlights underreporting of clozapine in other Western European countries compared to the UK

Schizophrenia Research, Journal Year: 2023, Volume and Issue: 268, P. 175 - 188

Published: Dec. 7, 2023

Pharmacovigilance studies indicate clozapine history is marked by adverse drug reactions (ADRs).

Language: Английский

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Clozapine-associated pericarditis and pancreatitis in children and adolescents: A systematic literature review and pharmacovigilance study using the VigiBase database

Schizophrenia Research, Journal Year: 2023, Volume and Issue: 268, P. 118 - 130

Published: Nov. 18, 2023

The literature has paid very little attention to pericarditis, pericardial effusion and pancreatitis during clozapine treatment in children adolescents.

Language: Английский

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Investigating in VigiBase® over 6000 cases of pneumonia in clozapine-treated patients in the context of the literature: focus on high lethality and the association with aspiration pneumonia

Expert Opinion on Drug Metabolism & Toxicology, Journal Year: 2024, Volume and Issue: 20(8), P. 857 - 871

Published: June 26, 2024

The literature associates clozapine with pneumonia/aspiration pneumonia.

Language: Английский

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Pharmacovigilance in Action: Utilizing VigiBase Data to Improve Clozapine Safety

Patient Preference and Adherence, Journal Year: 2024, Volume and Issue: Volume 18, P. 2261 - 2280

Published: Nov. 1, 2024

Clozapine is an antipsychotic which was approved in 1989 for treatment-resistant schizophrenia the United States (US). There were few randomized trials before its approval and potentially lethal clozapine adverse drug reactions (ADRs), such as agranulocytosis myocarditis identified by pharmacovigilance. VigiBase, WHO global database, a cornerstone of international pharmacovigilance efforts ADR identification during post-marketing surveillance. This systematic review literature explores additional contributions to knowledge ADRs from recent VigiBase studies.

Language: Английский

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Clinical and Demographic Predictors of Early Clozapine Discontinuation Across Mood and Psychotic Disorders

Journal of Clinical Psychopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Clozapine is effective for treatment-resistant schizophrenia and bipolar disorder but often discontinued due to adverse effects. This study compared early clozapine discontinuation rates reasons in patients with mood psychotic disorders. Data from all individuals or disorders who initiated the first time at inpatient psychiatric unit of Mayo Clinic, Rochester, Minnesota, between 2014 2022 were retrospectively analyzed. Early discontinuation, defined as within 90 days initiation, was primary outcome. Cox proportional hazards regression used assess factors associated discontinuation. Of 83 (mood group n = 37, psychosis 46), those older (P 0.022) more likely be nonsmokers 0.034). The overall 90-day rate 45.7%. significantly higher than (hazard ratio 2.41, 95% confidence interval 1.26-4.64, P 0.008). Other female sex 0.033), age 0.026), nonsmoking 0.001). In multivariable analysis, smoking status only factor inversely 0.47, 0.22-0.99, 0.048), while diagnostic group, sex, did not show significant associations (all > 0.05). Discontinuations primarily drug reactions both groups. Nearly half early, group. Studies should further explore potential pharmacodynamic pharmacokinetic including influence smoking. Careful monitoring personalized management side effects are crucial optimizing therapy improving treatment outcomes.

Language: Английский

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Association between the COX-2 rs689466 polymorphism and antipsychotic treatment: Impact on HDL cholesterol changes in clozapine-treated psychosis patients

Prostaglandins Leukotrienes and Essential Fatty Acids, Journal Year: 2025, Volume and Issue: unknown, P. 102665 - 102665

Published: Jan. 1, 2025

Language: Английский

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Letter to the FDA Proposing Major Changes in the US Clozapine Package Insert Supported by Clozapine Experts Worldwide. Part I

Journal of Clinical Psychopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Abstract Purpose/Background Clozapine was approved in the United States (US) using 1989 regulations and knowledge. After 30 years, many sections of US package insert (PI) are outdated. Methods We comprehensively reviewed literature to propose PI updates. present information 2 articles. In Part I, we focus on basic pharmacology based 407 relevant II focuses clinical aspects pharmacovigilance. Findings/Results Based more recent expectations Food Drug Administration regulations, clozapine including following: 1) clearance, 2) pharmacokinetics pharmacodynamics, 3) monitoring tools. identified 9 major problems pharmacological vivo studies indicate that is dependent CYP1A2 for its metabolism, minor role CYP2D6 metabolism requires removing recommendation lower doses poor metabolizers, nontoxic concentrations CYP3A4 has a potent inhibitors lack clinically effects, 4) several drug-drug interactions need be updated literature, 5) systemic inflammation may decrease increase risk intoxication, 6) obesity 7) patients Asian Indigenous American ancestry doses, 8) personalized titration c-reactive protein should considered until prospective available, 9) half-life section needs modified acknowledge single dosing at night frequent US. Implications/Conclusions An improvement lead PIs worldwide.

Language: Английский

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