"Most of the studies, even in adults, are cross-sectional or based upon pharmacoepidemiologic data; there is very little prospective data available on these very important [safety] issues," he said. "And there is not a single study in kids that is prospective. So we can inform the field."
In April at the XX International Congress on Schizophrenia Research in Savannah, Ga., Correll presented a subanalysis of 93 antipsychotic-naive children taking olanzapine(Drug information on olanzapine), risperidone(Drug information on risperidone) or quetiapine(Drug information on quetiapine), reporting the effects of those SGAs on glucose metabolism and insulin resistance (Correll et al., 2005a). Being antipsychotic naive is important, Correll said, because there is the debate as to whether it is the underlying illness, the patient's lifestyle/behavior or the drugs that cause the insulin resistance, which is a precursor for diabetes and metabolic syndrome.
"We have people who are young and start out often not being obese, and then we follow them for several months, so we will be able more to determine the effect of the medications," he said.
In the subanalysis presented in April, the researchers reported on 93 participants who ranged in age from 5 to 18 (mean age=14.1±3.4) and who had psychotic, mood and/or disruptive behavior spectrum disorders (Correll et al., 2005a). More than half (54.8%) were male and 46.2% were white.
Participants' height, weight, fat mass and percentage (via impedantiometry), waist circumference, fasting glucose, insulin, prolactin, leptin, and SGA levels (ensuring compliance) had been measured at baseline and at four and 12 weeks. The homeostatic model (HOMA-IR=insulin umol x glucose mmol/22.5) was used to calculated insulin resistance.
In the antipsychotic-naive youngsters treated with risperidone (n=51), olanzapine (n=30) or quetiapine (n=12) for eight to 13 weeks, fasting glucose, insulin and insulin resistance increased significantly. One premorbidly obese youngster (1.1%) developed diabetes on quetiapine. Medications did not differ in their effect on glucose and insulin, or on absolute and relative HOMA-IR changes (olanzapine=0.81±1.6, 62.2%; quetiapine=0.95±-2.4, 19.1%; risperidone=0.30±1.5, 32.0%).
When individual SGAs were considered, increases in glucose reached significance only for risperidone, while changes in insulin and HOMA-IR were only significant for olanzapine. Glucose increase was correlated with low baseline glucose levels and male gender (R2=0.48, p<0.0001), while an increase in HOMA-IR was correlated with weight gain and a diagnosis of disruptive behavior disorders (R2=0.21, p<0.0001).
Based on their subanalysis, the researchers concluded, "Increased insulin resistance in young people after three months of treatment with olanzapine, risperidone or quetiapine ... is of considerable concern." They recommended that clinicians institute routine monitoring of weight and glucose metabolism in this population.