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

ArticleinChild and Adolescent Psychiatric Clinics of North America 15(1):135-59 · February 2006with7 Reads
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.
    • "Since 1990, the Child Psychiatry Branch at the National Institute of Mental Health (NIMH) in Bethesda, MD has been conducting an ongoing study of COS. When compared to adult-onset schizophrenia (AOS), COS is often associated with more severe symptomatology and chronic disability (Nicolson et al., 2000, Kranzler et al., 2006). Despite the advent of multiple first and second generation antipsychotics, many children and adolescents with COS require long term treatment (Kranzler et al., 2005). "
    [Show abstract] [Hide abstract] ABSTRACT: Clozapine, a dibenzodiazepine antipsychotic, is the most effective medication for treatment-resistant schizophrenia. However, its use has been limited by the high risk of neutropenia. In children, the rate of neutropenia is higher when compared to adults. We decided to explore the use of lithium to manage neutropenia in childhood-onset schizophrenia (COS) through a systematic audit of COS cases. Medical records were reviewed for patients with COS who had been treated with the combination of clozapine and lithium carbonate. Seven patients were found to have been treated with both clozapine and lithium. After initiation of lithium, ANC increased significantly in six out of seven subjects by 29 to 106% with a mean of 66%. In addition, six out of seven subjects continued using both clozapine and lithium for over 2 years (range: 2.0-7.2 years) and do not have immediate plans for discontinuation of either medications. Our study bolsters support for the use of lithium in the management of neutropenia in children treated with clozapine. Although the coadministration of lithium and clozapine appears effective in the management of neutropenia, it is not without its risks and clinicians must be diligent in their joint use of these medications.
    Full-text · Article · Oct 2009
    • "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]. "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Feb 2009
  • [Show abstract] [Hide abstract] 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.
    Article · Apr 2007
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