In a related subanalysis, data were presented on dyslipidemia in a larger set of 258 youngsters (mean age=13.8 ±3.5, 62.0% male, 47.9% white) who completed eight to 13 weeks of treatment with aripiprazole(Drug information on aripiprazole) (n=48), olanzapine(Drug information on olanzapine) (n=66), quetiapine (n=51), risperidone(Drug information on risperidone) (n=81) or ziprasidone(Drug information on ziprasidone) (n=12) (Olshanskiy et al., 2005). Dyslipidemia was defined as fasting cholesterol 200 mg/dL and/or triglycerides 150 mg/dL. Participants' height, weight, body mass index (BMI), fat mass (bioimpedantiometry), waist circumference, lipid profile, leptin and SGA levels (assessing compliance) were measured at baseline and monthly thereafter. With regard to the entire group, none of the individual lipid parameters increased significantly from baseline to end point, but 19.2% of youths developed new-onset dyslipidemia, without statistical differences between the medication groups.
Correll presented data from a larger cohort of that same study at the Society of Biological Psychiatry meeting and at the American Psychiatric Association meeting, both held in Atlanta. In an abstract prepared for the biological psychiatry meeting, the investigators discussed dyslipidemia in 131 antipsychotic-naive youngsters (mean age=14.1±3.5, 64.9% male, 49.6% white) treated with aripiprazole (n=15), olanzapine (n=37), quetiapine(Drug information on quetiapine) (n=15) or risperidone (n=64) for eight to 14 weeks (Correll et al., 2005b). They concluded, "New-onset dyslipidemia is a relevant side effect of SGA treatment in antipsychotic-naive youths." In the total group, fasting total cholesterol and triglycerides increased significantly compared to baseline.
Analyzing changes for each SGA, lipid increases in total cholesterol low-density lipoprotein (LDL) cholesterol and triglycerides were significant only for olanzapine. Differences between medications reached significance regarding total cholesterol and LDL cholesterol, with olanzapine causing significantly greater increases than risperidone. However, as reported in the earlier group of patients with mixed treatment histories (Olshanskiy et al., 2005), the rates of new-onset dyslipidemia in antipsychotic-naive youths were not different between groups.
Using logistic regression, cholesterol increase was correlated with low baseline cholesterol levels and weight gain. Increases in triglycerides were correlated with weight gain, low baseline triglycerides, divalproex (Depakote) co-treatment, and Asian or African-American race. Also, new-onset dyslipidemia was associated with weight gain and co-treatment with divalproex. Overall, the investigators recommended more frequent lipid monitoring.
At that same meeting, Correll presented data showing that SGAs can adversely affect body composition in children and adolescents (Correll et al., 2005c). Correll and colleagues analyzed prospective data from 301 youngsters, ranging in age from 4 to 19 (mean age=13.7±3.5) who had a DSM-IV diagnosis of schizophrenia spectrum (31.0%), mood (41.1%) or disruptive behavior (27.9%) disorders requiring initiation of SGA treatment. Of the participants, 63.3% were postpubertal, 64.7% were male, and 47.5% were white. They had completed eight to 14 weeks of SGA treatment.
According to Correll, in the entire sample--which included switchers and pretreated individuals as well as antipsychotic-naive participants--body weight, fat mass and waist circumference increased significantly for all SGAs, except aripiprazole, while BMI percentiles increased significantly only for patients on olanzapine and risperidone.
When switchers and pretreated youngsters were removed from the analyses, weight as well as age -and sex-adjusted BMI percentiles increased with all atypical antipsychotic drugs for which data in a sufficient number of never-treated youths were available (i.e., aripiprazole, olanzapine, quetiapine and risperidone). Individuals found to be at high-risk for adverse changes in body composition included those who were antipsychotic-naive, were older with schizophrenia or mood disorders, were treated with olanzapine, were relatively leptin-resistant, and experienced significant early weight gain.
Asked what clinicians should be aware of in terms of treating children and adolescents with second-generation antipsychotics, Correll responded that while novel antipsychotics have been shown to be effective for a number of psychiatric conditions, including nonpsychotic disorders, clinicians have to carefully weigh the risks and benefits of these treatments.