Benefit-Risk Assessment of Atypical Antipsychotics in the Treatment of Schizophrenia and Comorbid Disorders in Children and Adolescents

Abstract

Evidence on the efficacy and safety of atypical antipsychotics in children and adolescents with schizophrenia is limited. The purpose of this review is to assess the published data on the use of atypical antipsychotics in children and adolescents with schizophrenia alone and with comorbid disorders, and to establish benefit-risk guidelines for clinicians.Risperidone, olanzapine and clozapine were found to be effective in the treatment of aggression and mania. Risperidone, and possibly also olanzapine, may be the drugs of choice in children with comorbid tic disorders. Ziprasidone has some monoamine reuptake inhibition properties and may be administered as an augmenting agent in children and adolescents with schizophrenia and comorbid anxiety and mood disorders. Compared with the typical antipsychotics, the atypical drugs seem to be more effective, better tolerated and lead to better patient adherence. Importantly, the atypical antipsychotics have a lower propensity to induce extrapyramidal symptoms and a potential (shown so far only in adults) to improve cognitive function and inhibit suicidal behaviour (especially clozapine). Yet, the adverse effects associated with these agents, especially weight gain, which may also have long-term effects, can lead to non-compliance in the young population. In children and adolescents receiving clozapine, olanzapine and quetiapine (but not ziprasidone, which does not have a pro-appetite effect), particularly those with obesity or a family history of diabetes mellitus, fasting blood glucose and lipid levels must be monitored frequently. Weight gain might be better controlled when the children and their parents are properly informed about this adverse effect and diet is regulated. Another major disadvantage of the atypical antipsychotics, especially risperidone, is their association with hyperprolactinaemia, which can lead to hypogonadism-induced osteoporosis, galactorrhoea, gynaecomastia, irregular menstruation and sexual dysfunction, all seen also with typical antipsychotics. Other atypical antipsychotics, namely olanzapine and ziprasidone, have been reported to be prolactin sparing in adults, but may not be completely devoid of hyperprolactinaemic effects in children and adolescents. Thus, prolactin levels should be assessed routinely in young patients treated with atypical antipsychotics. Further, children and adolescents with hyperprolactinaemia-related effects should be switched to a prolactin-sparing agent, such as quetiapine. All atypical antipsychotics may induce sedation and they are not devoid of extrapyramidal symptoms (especially risperidone). The use of typical antipsychotics has been limited to patients who are resistant to atypical antipsychotics, intolerant to their adverse effects, or require injections or depot preparations. Further double-blind, placebo-controlled trials and long-term safety assessments are needed before definitive conclusions can be reached about the place of atypical antipsychotics in the therapeutic armamentarium of childhood-onset schizop...

Use and tolerability of newer antipsychotics and antidepressants: a chart review in a paediatric setting

“…Despite small sample size, our analysis supports the results from previous study that risperidone is more likely to induce hyperprolactinemia than other atypical antipsychotics [24,25]. Since hyperprolactinemia in children and adolescents might lead to galactorrhoea, gynaecomastia, irregular menstruation and sexual dysfunction, it is recommended to routinely monitor prolactin levels in paediatric patients treated with any atypical antipsychotic, particularly during the first phases of therapy [26].…”

National Trends in the Outpatient Treatment of Children and Adolescents With Antipsychotic Drugs

“…17,18 Adverse metabolic effects of some secondgeneration antipsychotic medications may be even more severe in children and adolescents than in adults. [19][20][21][22][23] Consistent with previous studies of public 3 and commercially insured 4 youth, antipsychotic treatment was significantly more common in mental health visits by male patients than by female patients. Although this sex difference might be partially explained by the antipsychotic treatment of tic disorders, pervasive developmental disorders, or disruptive behavior disorders, all of which are more common in boys than girls, [24][25][26][27][28] mental health visits by male subjects remained significantly more likely to include antipsychotic treatment after controlling for these and other diagnoses.…”

Child and Adolescent Psychiatrists' Reported Monitoring Behaviors for Second-Generation Antipsychotics

“…However, our response rate parallels other surveys conducted using the AMA mailing list (Needle et al 2012) and the sex and age distribution from our sample were similar to that from the American Association of Medical Colleges' 2012 Physician Specialty list. (American Association of Medical Colleges, 2012) Further, research has highlighted different safety profiles across the SGAs (Stigler et al 2001;Schur et al 2003;Newcomer et al 2004;Toren et al 2004). However, questions about specific monitoring practices with individual SGAs was beyond the scope of this survey.…”