Clozapine for Treatment-Resistant Disruptive Behaviors in Youths With Autism Spectrum Disorder Aged 10-17 Years: Protocol for an Open-Label Trial
BackgroundAutism Spectrum Disorder (ASD) is a complex neurodevelopmental condition emerging in early childhood, characterized by core features such as sociocommunicative deficits and repetitive, rigid behaviors, interests, and activities. In addition to these, disruptive beha...
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JMIR Publications
2025-01-01
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| Online Access: | https://www.researchprotocols.org/2025/1/e58031 |
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| author | André Luiz Schuh Teixeira da Rosa Marina Ribeiro Barreto da Costa Gabriela Bezerra Sorato Felipe de Moura Manjabosco Érica Bonganhi de Bem Lucas Dellazari Arthur Bezerra Falcão Lucas de Oliveira Cia Olivia Sorato Bezerra Rogério Boff Borges Luis Augusto Rohde Ana Soledade Graeff-Martins |
| author_facet | André Luiz Schuh Teixeira da Rosa Marina Ribeiro Barreto da Costa Gabriela Bezerra Sorato Felipe de Moura Manjabosco Érica Bonganhi de Bem Lucas Dellazari Arthur Bezerra Falcão Lucas de Oliveira Cia Olivia Sorato Bezerra Rogério Boff Borges Luis Augusto Rohde Ana Soledade Graeff-Martins |
| author_sort | André Luiz Schuh Teixeira da Rosa |
| collection | DOAJ |
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BackgroundAutism Spectrum Disorder (ASD) is a complex neurodevelopmental condition emerging in early childhood, characterized by core features such as sociocommunicative deficits and repetitive, rigid behaviors, interests, and activities. In addition to these, disruptive behaviors (DB), including aggression, self-injury, and severe tantrums, are frequently observed in pediatric patients with ASD. The atypical antipsychotics risperidone and aripiprazole, currently the only Food and Drug Administration–approved treatments for severe DB in patients with ASD, often encounter therapeutic failure or intolerance. Given this, exploring pharmacological alternatives for more effective management of DB associated with ASD is essential. Clozapine, noted for its unique antiaggressive effects in schizophrenia and in various treatment-resistant neuropsychiatric disorders, independent from its antipsychotic efficacy, remains underexplored in youths with ASD facing severe and persistent DB.
ObjectiveThis study aimed to evaluate the efficacy, tolerability, and safety of clozapine for treatment-resistant DB in youths with ASD.
MethodsThis is a prospective, single-center, noncontrolled, open-label trial. After a cross-titration phase, 31 patients with ASD aged 10-17 years and with treatment-resistant DB received a flexible dosage regimen of clozapine (up to 600 mg/day) for 12 weeks. Standardized instruments were applied before, during, and after the treatment, and rigorous clinical monitoring was performed weekly. The primary outcome was assessed using the Irritability Subscale of the Aberrant Behavior Checklist. Other efficacy measures include the Clinical Global Impression Severity and Improvement, the Swanson, Nolan, and Pelham questionnaire-IV, the Childhood Autism Rating Scale, and the Vineland Adaptive Behavior Scale. Safety and tolerability measures comprised adverse events, vital signs, electrocardiography, laboratory tests, physical measurements, and extrapyramidal symptoms with the Simpsons-Angus Scale. Statistical analysis will include chi-square tests with Monte Carlo simulation for categorical variables, paired t tests or Wilcoxon tests for continuous variables, and multivariate linear mixed models to evaluate the primary outcome, adjusting for confounders.
ResultsRecruitment commenced in February 2023. Data collection was concluded by April 2024, with analysis ongoing. This article presents the protocol of the initially planned study to provide a detailed methodological description. The results of this trial will be published in a future paper.
ConclusionsThe urgent need for effective pharmacological therapies in mitigating treatment-resistant DB in pediatric patients with ASD underscores the importance of this research. Our study represents the first open-label trial to explore the anti-aggressive effects of clozapine in this specific demographic, marking a pioneering step in clinical investigation. Adopting a pragmatic approach, this trial protocol aims to mirror real-world clinical settings, thereby enhancing the applicability and relevance of our findings. The preliminary nature of future results from this research has the potential to pave the way for more robust studies and emphasize the need for continued innovation in ASD treatment.
Trial RegistrationBrazilian Clinical Trials Registry RBR-54j3726; https://ensaiosclinicos.gov.br/rg/RBR-54j3726
International Registered Report Identifier (IRRID)DERR1-10.2196/58031 |
| format | Article |
| id | doaj-art-b1ae6eb513014cacbf0ec0629d1727ce |
| institution | Kabale University |
| issn | 1929-0748 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | JMIR Publications |
| record_format | Article |
| series | JMIR Research Protocols |
| spelling | doaj-art-b1ae6eb513014cacbf0ec0629d1727ce2025-01-30T20:30:32ZengJMIR PublicationsJMIR Research Protocols1929-07482025-01-0114e5803110.2196/58031Clozapine for Treatment-Resistant Disruptive Behaviors in Youths With Autism Spectrum Disorder Aged 10-17 Years: Protocol for an Open-Label TrialAndré Luiz Schuh Teixeira da Rosahttps://orcid.org/0000-0003-4677-3562Marina Ribeiro Barreto da Costahttps://orcid.org/0000-0001-7388-1142Gabriela Bezerra Soratohttps://orcid.org/0009-0004-5798-9689Felipe de Moura Manjaboscohttps://orcid.org/0009-0003-8984-7995Érica Bonganhi de Bemhttps://orcid.org/0009-0000-2516-4229Lucas Dellazarihttps://orcid.org/0009-0008-8702-0827Arthur Bezerra Falcãohttps://orcid.org/0000-0002-5224-8708Lucas de Oliveira Ciahttps://orcid.org/0009-0003-6219-2095Olivia Sorato Bezerrahttps://orcid.org/0009-0004-1769-662XRogério Boff Borgeshttps://orcid.org/0000-0002-2548-1889Luis Augusto Rohdehttps://orcid.org/0000-0002-4552-4188Ana Soledade Graeff-Martinshttps://orcid.org/0000-0002-0108-1469 BackgroundAutism Spectrum Disorder (ASD) is a complex neurodevelopmental condition emerging in early childhood, characterized by core features such as sociocommunicative deficits and repetitive, rigid behaviors, interests, and activities. In addition to these, disruptive behaviors (DB), including aggression, self-injury, and severe tantrums, are frequently observed in pediatric patients with ASD. The atypical antipsychotics risperidone and aripiprazole, currently the only Food and Drug Administration–approved treatments for severe DB in patients with ASD, often encounter therapeutic failure or intolerance. Given this, exploring pharmacological alternatives for more effective management of DB associated with ASD is essential. Clozapine, noted for its unique antiaggressive effects in schizophrenia and in various treatment-resistant neuropsychiatric disorders, independent from its antipsychotic efficacy, remains underexplored in youths with ASD facing severe and persistent DB. ObjectiveThis study aimed to evaluate the efficacy, tolerability, and safety of clozapine for treatment-resistant DB in youths with ASD. MethodsThis is a prospective, single-center, noncontrolled, open-label trial. After a cross-titration phase, 31 patients with ASD aged 10-17 years and with treatment-resistant DB received a flexible dosage regimen of clozapine (up to 600 mg/day) for 12 weeks. Standardized instruments were applied before, during, and after the treatment, and rigorous clinical monitoring was performed weekly. The primary outcome was assessed using the Irritability Subscale of the Aberrant Behavior Checklist. Other efficacy measures include the Clinical Global Impression Severity and Improvement, the Swanson, Nolan, and Pelham questionnaire-IV, the Childhood Autism Rating Scale, and the Vineland Adaptive Behavior Scale. Safety and tolerability measures comprised adverse events, vital signs, electrocardiography, laboratory tests, physical measurements, and extrapyramidal symptoms with the Simpsons-Angus Scale. Statistical analysis will include chi-square tests with Monte Carlo simulation for categorical variables, paired t tests or Wilcoxon tests for continuous variables, and multivariate linear mixed models to evaluate the primary outcome, adjusting for confounders. ResultsRecruitment commenced in February 2023. Data collection was concluded by April 2024, with analysis ongoing. This article presents the protocol of the initially planned study to provide a detailed methodological description. The results of this trial will be published in a future paper. ConclusionsThe urgent need for effective pharmacological therapies in mitigating treatment-resistant DB in pediatric patients with ASD underscores the importance of this research. Our study represents the first open-label trial to explore the anti-aggressive effects of clozapine in this specific demographic, marking a pioneering step in clinical investigation. Adopting a pragmatic approach, this trial protocol aims to mirror real-world clinical settings, thereby enhancing the applicability and relevance of our findings. The preliminary nature of future results from this research has the potential to pave the way for more robust studies and emphasize the need for continued innovation in ASD treatment. Trial RegistrationBrazilian Clinical Trials Registry RBR-54j3726; https://ensaiosclinicos.gov.br/rg/RBR-54j3726 International Registered Report Identifier (IRRID)DERR1-10.2196/58031https://www.researchprotocols.org/2025/1/e58031 |
| spellingShingle | André Luiz Schuh Teixeira da Rosa Marina Ribeiro Barreto da Costa Gabriela Bezerra Sorato Felipe de Moura Manjabosco Érica Bonganhi de Bem Lucas Dellazari Arthur Bezerra Falcão Lucas de Oliveira Cia Olivia Sorato Bezerra Rogério Boff Borges Luis Augusto Rohde Ana Soledade Graeff-Martins Clozapine for Treatment-Resistant Disruptive Behaviors in Youths With Autism Spectrum Disorder Aged 10-17 Years: Protocol for an Open-Label Trial JMIR Research Protocols |
| title | Clozapine for Treatment-Resistant Disruptive Behaviors in Youths With Autism Spectrum Disorder Aged 10-17 Years: Protocol for an Open-Label Trial |
| title_full | Clozapine for Treatment-Resistant Disruptive Behaviors in Youths With Autism Spectrum Disorder Aged 10-17 Years: Protocol for an Open-Label Trial |
| title_fullStr | Clozapine for Treatment-Resistant Disruptive Behaviors in Youths With Autism Spectrum Disorder Aged 10-17 Years: Protocol for an Open-Label Trial |
| title_full_unstemmed | Clozapine for Treatment-Resistant Disruptive Behaviors in Youths With Autism Spectrum Disorder Aged 10-17 Years: Protocol for an Open-Label Trial |
| title_short | Clozapine for Treatment-Resistant Disruptive Behaviors in Youths With Autism Spectrum Disorder Aged 10-17 Years: Protocol for an Open-Label Trial |
| title_sort | clozapine for treatment resistant disruptive behaviors in youths with autism spectrum disorder aged 10 17 years protocol for an open label trial |
| url | https://www.researchprotocols.org/2025/1/e58031 |
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