Metabolic and endocrine adverse effects of second-generation antipsychotics in children and adolescents: A systematic review of randomized, placebo controlled trials and guidelines for clinical practice

Abstract

Second-generation antipsychotics (SGA) are being used more often than ever before in children and adolescents with psychotic and a wide range of non-psychotic disorders. Several SGA have received regulatory approval for some paediatric indications in various countries, but off-label use is still frequent. The aim of this paper was to perform a systematic review and critically evaluate the literature on cardiometabolic and endocrine side-effects of SGA in children and adolescents through a Medline/Pubmed/Google Scholar search of randomized, placebo controlled trials of antipsychotics in children and adolescents (<18 years old) until February 2010. In total, 31 randomized, controlled studies including 3595 paediatric patients were identified. A review of these data confirmed that SGA are associated with relevant cardiometabolic and endocrine side-effects, and that children and adolescents have a high liability to experience antipsychotic induced hyperprolactinaemia, weight gain and associated metabolic disturbances. Only weight change data were sufficiently reported to conduct a formal meta-analysis. In 24 trials of 3048 paediatric patients with varying ages and diagnoses, ziprasidone was associated with the lowest weight gain (-0.04kg, 95% confidence interval [CI]: -0.38 to +0.30), followed by aripiprazole (0.79kg, 95% CI: 0.54 to 1.04], quetiapine (1.43kg, 95% CI: 1.17 to 1.69) and risperidone (1.76kg, 95% CI: 1.27 to 2.25) were intermediate, and olanzapine was associated with weight gain the most (3.45kg, 95% CI: 2.93 to 3.97). Significant weight gain appeared to be more prevalent in patients with autistic disorder who were also younger and likely less exposed to antipsychotics previously. These data clearly suggest that close screening and monitoring of metabolic side effects is warranted and that the least cardiometabolically problematic agents should be used first whenever possible. A good collaboration between child- and adolescent psychiatrists, general practitioners and paediatricians is essential to maximize overall outcomes and to reduce the likelihood of premature cardiovascular morbidity and mortality.

Antipsychotic Medication Prescribing in Children Enrolled in Medicaid

“…[11][12][13]. Best practice guidelines were considered as being met if the clinician indicated that he or she was performing a regular laboratory evaluation or was aware that another physician was performing it.…”

“…[9][10][11] Another source of concern pertains to the adverse effects of antipsychotic medications, some of which may be more common in youth compared with adults. These adverse effects include movement disorders, 12 metabolic problems, weight gain, 13 and sedation.…”

Clinical use of second-generation antipsychotics in children

“…Various studies show that the significant risk for metabolic and other SGA-induced adverse effects calls for appropriate monitoring (34)(35)(36)(37)(38). However, the content and schedule of the physical evaluations and follow-up practices of SGA medications have been diverse in child psychiatric clinical work (7,39,(44)(45)(46), as was also observed in this study.…”

“…Sedation, hyperprolactinemia, and metabolic disturbances, such as weight gain, dyslipidaemia, and hyperglycaemia, are known SGA adverse effects that can have far-reaching consequences through metabolic, endocrinological, cardiovascular, and psychological effects (34)(35)(36)(37)(38). We also know very little about the long-term effects of SGAs on the developing central nervous system.…”

Maculopapular rash associated with risperidone in a child

“…Risperidone is used for many indications in children and adolescents. These indications include bipolar mania, schizophrenia, disruptive behaviour disorders, and aggression associated with autism spectrum disorder/mental retardation [5].…”