Treatment-Refractory Schizophrenia in Children and Adolescents: An Update on Clozapine and Other Pharmacologic Interventions

Department of Psychiatry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Child and Adolescent Psychiatric Clinics of North America (Impact Factor: 2.6). 02/2006; 15(1):135-59. DOI: 10.1016/j.chc.2005.08.008
Source: PubMed


Treatment-refractory early-onset schizophrenia is a rare but severe form of the disorder associated with poor premorbid function and long-term disability. The currently available evidence suggests that clozapine remains the most efficacious treatment for the amelioration of both positive and negative symptoms of the disorder and problematic aggressive behaviors. Clozapine use in children and adolescents, however, is limited by its association with hematologic adverse events and an increased frequency of seizure activity. Further studies are needed to examine the usefulness of antipsychotic combinations and of augmentation therapies to antipsychotic medications in order to treat persistent residual psychotic symptoms in children and adolescents who have schizophrenia and who have not responded to several sequential trials of antipsychotic monotherapy.

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    • "Pour les enfants pharmacorésistants , la clozapine peut enfin être proposée en troisième intention [16]. Cet antipsychotique reste cependant, difficile d'emploi en raison de la surveillance biologique qu'il nécessite et des risques induits de crise convulsive, de myocardite et d'agranulocytose [17]. Une alternative à la chimiothérapie est apparue récemment avec l'utilisation de la stimulation magnétique transcrânienne (SMT) dans le traitement des hallucinations auditives pharmacorésistantes de l'adulte [18]. "
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    ABSTRACT: Auditory-Verbal Hallucinations (AVH) constitute extremely frequent positive symptoms in early-onset schizophrenia. These symptoms are all the more invalidating as they are often drug-resistant. The procedure of repetitive transcranial magnetic stimulation (rTMS), used in such cases in adult subjects with schizophrenia, showed good efficiency and tolerability. We present here the case of an 11-year-old child with a diagnosis of very-early onset schizophrenia including florid AVH and a massive delusion of alien control. His hallucinatory syndrome resistant to the antipsychotic treatments was considerably reduced by rTMS. This treatment allowed this child to attend school and to follow regular psychotherapeutic sessions. The spectacular and rapid response to rTMS reported here indicates that rTMS should occupy in future years a key role in the treatment of AVH in very early onset schizophrenia.
    Neuropsychiatrie de l Enfance et de l Adolescence 02/2009; 57(1):38–43. DOI:10.1016/j.neurenf.2007.07.017
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    ABSTRACT: This article presents responses to the question of whether clozapine is ever appropriate to use in the pediatric population. Among others, Jean A. Frazier also agreed that clozapine is appropriate for use in the pediatric population. Clozapine has truly revolutionized the treatment of refractory patients with schizophrenia at any age. This agent was approved by the U.S. Food and Drug Administration (FDA) in 1989 for use in individuals ages 18 years or older with treatment refractory schizophrenia. Subsequent to clozapine, the FDA has approved a number of atypical antipsychotics for the treatment of psychotic disorders, but none to date are approved for use in children and adolescents. Despite the superior efficacy of clozapine, its use has been limited because of its complex side effect profile, consisting of hypersalivation, weight gain, metabolic abnormalities, cardiovascular side effects, sedation, seizures, and agranulocytosis. Children may be more prone to developing these side effects than adults because of developmental differences in the metabolism of this agent.
    Journal of the American Academy of Child & Adolescent Psychiatry 04/2007; 46(3):423-8. DOI:10.1097/chi.0b013e3180ed94e · 7.26 Impact Factor
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    ABSTRACT: To describe self-reported patterns of prescribing atypical antipsychotics (ATAs) and monitoring practices of child psychiatrists and developmental pediatricians in Canada. We surveyed members of the Canadian Academy of Child and Adolescent Psychiatry and members of the Developmental Paediatrics Section of the Canadian Paediatric Society regarding the types and frequencies of ATAs they prescribed, the ages and diagnoses of patients for whom they prescribed these medications, and the types and frequencies of monitoring used. Ninety-four percent of the child psychiatrists (95% CI, 90% to 97%) and 89% of the developmental pediatricians (95% CI, 75% to 96%) prescribed ATAs, most commonly risperidone (69%). Diagnoses included psychotic, mood, anxiety, externalizing, and pervasive developmental disorders. Prescribing for symptoms such as aggression, low frustration tolerance, and affect dysregulation was also common. Twelve percent of all prescriptions were for children under age 9 years. Most clinicians monitored patients, but there were wide variations in the type and frequency of tests performed. Despite the lack of formal indications, ATAs were prescribed by this group of clinicians for many off-label indications in youth under age 18 years, including very young children. Neither evidence-based guidelines nor a consensus on monitoring exist for this age group.
    Canadian journal of psychiatry. Revue canadienne de psychiatrie 07/2007; 52(6):363-8. · 2.55 Impact Factor
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