4.54 a Retrospective Review of Clozapine use in Children and Adolescents

Komaryk, Ardelle L.D.; Elbe, Dean; Burgess, Leah

doi:10.1016/j.jaac.2019.08.294

Cited by 4 publications

(4 citation statements)

References 31 publications

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“…The level of response was determined by the differences in the CGI and CGAS scales before the pharmacogenetic intervention (basal) and after at least eight weeks of the resulting intervention (clinical dose adjustment or treatment change). Improvements of 3 or more in the CGI scores and of 20 or more in the CGAS scores were considered significant as the patient reached stabilisation and required less medical attention (no hospitalisation, less frequent visits to their clinician and no change or additional medication) [ 22 ]. Figure 1 and Figure 2 represent the changes in the CGI and CGAS scores pre- and post-pharmacogenetic intervention in the treatment-resistant cohort patients.…”

Section: Methodsmentioning

confidence: 99%

Pharmacogenetic Interventions Improve the Clinical Outcome of Treatment-Resistant Autistic Spectrum Disorder Sufferers

et al. 2022

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BACKGROUND: Autistic spectrum disorders (ASD) are severe neurodevelopmental alterations characterised by deficits in social communication and repetitive and restricted behaviours. About a third of patients receive pharmacological treatment for comorbid symptoms. However, 30–50% do not respond adequately and/or present severe and long-lasting side effects. METHODS: Genetic variants in CYP1A2, CYP2C19, CYP2D6 and SLC6A4 were investigated in N = 42 ASD sufferers resistant to pharmacological treatment. Clinical recommendations based on their pharmacogenetic profiles were provided within 24–48 h of receiving a biological sample. RESULTS: A total of 39 participants (93%) improved after the pharmacogenetic intervention according to their CGI scores (difference in basal-final scores: 2.26, SD 1.55) and 37 participants (88%) according to their CGAS scores (average improvement of 20.29, SD 11.85). Twenty-three of them (55%) achieved symptom stability (CGI ≤ 3 and CGAS improvement ≥ 20 points), requiring less frequent visits to their clinicians and hospital stays. Furthermore, the clinical improvement was higher than that observed in a control group (N = 62) with no pharmacogenetic interventions, in which 66% responded to treatment (difference in CGI scores: −0.87, SD 9.4, p = 1 × 10−5; difference in CGAS scores: 6.59, SD 7.76, p = 5 × 10−8). CONCLUSIONS: The implementation of pharmacogenetic interventions has the potential to significantly improve the clinical outcomes in severe comorbid ASD populations with drug treatment resistance and poor prognosis.

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Section: Methodsmentioning

confidence: 99%

Pharmacogenetic Interventions Improve the Clinical Outcome of Treatment-Resistant Autistic Spectrum Disorder Sufferers

et al. 2022

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“…Clozapine is an atypical antipsychotic effective in the treatment of refractory schizophrenia, schizoaffective disorder, and bipolar disorder in adults. [1][2][3] In children and adolescents, its use is supported by the recent literature 4,5 that has found significant improvement in negative 6 and positive symptoms. 7,8 Clozapine is superior to other atypical antipsychotics in psychosis.…”

Section: Introductionmentioning

confidence: 94%

A Systematic Review of Clozapine Concentration–Dose Ratio from Therapeutic Drug Monitoring Studies in Children and Adolescents Treated with Clozapine for Mental Disorders

Jiménez-Fernández,

Gurpegui,

Correll

et al. 2023

Therapeutic Drug Monitoring

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Background: Therapeutic drug monitoring of clozapine in children and adolescents has received insufficient attention. Calculation of concentration-to-dose (C/D) ratios from trough steady-state concentrations estimate drug clearance. Methods: A systematic electronic literature search was conducted in 3 article databases from inception until January 10, 2023, and articles reporting clozapine concentrations in children and adolescents were retrieved. The pharmacokinetic quality of the studies was assessed, and clozapine C/D ratios were calculated using the sample mean clozapine dose and concentration. Results: Of the 37 articles of potential interest, only 7 reported clozapine trough and steady-state concentrations. After excluding case reports and a study confounded by fluvoxamine, 4 studies on psychosis from Europe and the United States were included. The clozapine C/D ratios were similar to published adult values and ranged from 0.82 to 1.24 with a weighted mean of 1.08 ng/mL per mg/d. The weighted means were 334 mg/d for the dose and 380 ng/mL for the concentration. The stratified analysis of the weighted mean clozapine C/D ratios from 2 studies showed lower values in 52 male (1.05 ng/mL per mg/d) than in 46 female (1.46 ng/mL per mg/d) children and adolescents, with values similar to those reported for European adult nonsmokers. Two female adolescents had high clozapine C/D ratios (2.54 ng/mL per mg/d), an Asian American patient with borderline obesity and a patient with intellectual disability with low dosage (mean = 102 mg/d) and concentration (mean = 55 ng/mL). Conclusions: Reports on clozapine therapeutic drug monitoring in children and adolescents are limited in number and quality. Future studies should focus on basic pharmacokinetic issues, such as stratification by sex, smoking, and relevant comedications with inductive or inhibitory properties.

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“…There were no episodes of severe neutropenia, but a high rate of benign hematological adverse events was seen. The study concludes that most treatment-refractory children and adolescents requiring hospitalization improve with clozapine, and most were able to tolerate it despite high rates of largely manageable side effects [ 87 ].…”

Section: Reviewmentioning

confidence: 99%

Lost in Translation: Challenges in the Diagnosis and Treatment of Early-Onset Schizophrenia

Gupta¹,

Gupta²,

Esang³

2023

Cureus

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Early-onset schizophrenia (EOS) is a heterogeneous condition that has a serious, insidious clinical course and poor long-term mental health outcomes. The clinical presentations are highly complex due to the overlapping symptomatology with other illnesses, which contributes to a delay in the diagnosis. The objective of the review is to study if an earlier age of onset (AAO) of EOS has poor clinical outcomes, the diagnostic challenges of EOS, and effective treatment strategies. The review provides a comprehensive literature search of 5966 articles and summarizes 126 selected for empirical evidence to methodically consider challenges in diagnosing and treating EOS for practicing clinicians. The risk factors of EOS are unique but have been shared with many other neuropsychiatric illnesses. Most of the risk factors, including genetics and obstetric complications, are nonmodifiable. The role of early diagnosis in reducing the duration of untreated psychosis (DUP) remains critical to reducing overall morbidity. Many specific issues contribute to the risk and clinical outcomes. Therefore, issues around diagnostic ambiguity, treatment resistance, nonadherence, and rehospitalizations further extend the DUP. There is hesitancy to initiate clozapine early, even though the empirical evidence strongly supports its use. There is a growing body of research that suggests the use of long-acting injectables to address nonadherence, and these measures are largely underutilized in acute settings. The clinical presentations of EOS are complex. In addition to the presence of specific risk factors, patients with an early onset of illness are also at a higher risk for treatment resistance. While there is a need to develop tools for early diagnosis, established evidence-based measures to address nonadherence, psychoeducation, and resistance must be incorporated into the treatment planning.

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4.54 a Retrospective Review of Clozapine use in Children and Adolescents

Cited by 4 publications

References 31 publications

Pharmacogenetic Interventions Improve the Clinical Outcome of Treatment-Resistant Autistic Spectrum Disorder Sufferers

Pharmacogenetic Interventions Improve the Clinical Outcome of Treatment-Resistant Autistic Spectrum Disorder Sufferers

A Systematic Review of Clozapine Concentration–Dose Ratio from Therapeutic Drug Monitoring Studies in Children and Adolescents Treated with Clozapine for Mental Disorders

Lost in Translation: Challenges in the Diagnosis and Treatment of Early-Onset Schizophrenia

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