Cardiometabolic adverse reactions suspected of being associated with second-generation antipsychotics in children and adolescents
Excess weight and obesity in the general population are increasing problems throughout the Western world, and this rise has also been observed in children and adolescents.Weight gain and obesity are known to be associated with diabetes, dyslipidemia and hypertension. In addition, weight gain is a well-established adverse reaction to second-generation antipsychotics ( SGAs ).
In Canada, there are 7 marketed second-generation antipsychotics: Clozapine, Risperidone, Olanzapine, Quetiapine, Paliperidone, Ziprasidone and Aripiprazole. Their date of marketing ranges from 1991 ( Clozapine ) to 2009 ( Aripiprazole ).
Recently, Aripiprazole ( Abilify ) was authorized for the treatment of schizophrenia in adolescents 15 to 17 years old. Previously, there were no authorized indications for the use of SGAs in children or adolescents under 18 years of age in Canada.
Pediatric drug use, in many circumstances, has been based primarily on information extrapolated from studies involving adults, as well as from other types of scientific evidence, including case reports, open studies of clinical experience and controlled clinical trials.
Second-generation antipsychotics have been prescribed for children and adolescents with mental health problems such as schizophrenia, bipolar I disorder, autism, pervasive developmental disorder, disruptive behaviour disorders ( including conduct disorder and attention-deficit hyperactivity disorder ), developmental disabilities and Tourette syndrome. The use of these drugs in the pediatric population has increased substantially over the last decade. Despite this increased use, data regarding their safety are limited.
The cardiometabolic effects of second-generation antipsychotics in pediatric patients, including age-inappropriate weight gain, obesity, hypertension, and lipid and glucose abnormalities, are of concern. Furthermore, children and adolescents with mental health problems often have multiple cardiovascular risk factors, including poor nutrition, inadequate exercise, substance abuse and lack of adequate health care monitoring. Some studies have shown that youth using antipsychotic agents may be at a higher risk of weight gain and metabolic effects than adults who use the same drugs. If weight gain is established in youth, it tends to persist into adulthood.
Because of differences in absorption, distribution and metabolism of antipsychotics in the pediatric population, higher doses per weight are required than in adults to achieve similar efficacy. Cardiometabolic effects are problematic during childhood because they tend to be predictors of adult obesity, metabolic syndrome, hypertension, cardiovascular morbidity and malignant disease.
Adverse effects such as weight gain have been found to vary significantly by SGA agent. Clozapine and Olanzapine seem to be associated with the highest risk of clinically significant weight gain in children and adults. Risperidone and Quetiapine generally show modest risk, whereas Ziprasidone and Aripiprazole are associated with the lowest risk. Limited data are available for Paliperidone. The risk of lipid elevation and increased blood sugar appears to be greatest with Olanzapine.
Health Canada received 29 reports of cardiometabolic adverse reactions in children and adolescents under 18 years suspected of being associated with Clozapine ( n=3), Risperidone ( n=13 ), Olanzapine ( n=10 ) and Quetiapine ( n=4 ). None of the reports implicated Paliperidone, Ziprasidone or Aripiprazole. The case reports included one or more of weight gain, hyperglycemia or new-onset diabetes, hypertension and hyperlipidemia. Of these cases, 21 involved boys and 7 involved girls ( sex not specified in one report ). The median age of the patients was 14 years. Some reports indicated the use of concomitant medications known to cause weight gain. ( Xagena )
Source: Health Canada - CARN, 2012