BERLIN — The most common second-generation antipsychotics prescribed to young people with various psychotic, mood, and behavioral disorders adversely affect all components of body composition and lead to dyslipidemia in this patient population, a study has shown.
Youths who have never taken antipsychotics and those cotreated with olanzapine (Zyprexa) and divalproex (Depakote) who experience significant early weight gain are at highest risk for the metabolic changes, Christoph U. Correll, M.D., said in a presentation at the 16th World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions.
“Second-generation antipsychotics are widely used in young patients, but limited comparative data exist on their effects on body composition and lipid metabolism,” said Dr. Correll of Zucker Hillside Hospital in Glen Oaks, N.Y. He, along with his colleagues, prospectively evaluated the relative effects on these factors of olanzapine, risperidone (Risperdal), or quetiapine (Seroquel)—the three most widely prescribed drugs in this particular class.
The open-label study included youths between the ages of 5 and 18 years with a DSM-IV diagnosis of psychotic, mood, and/or disruptive behavior disorders who had begun or switched to treatment with one of the three medications within 7 days of the start of the investigation. Exclusion criteria included a history of any eating disorder, active thyroid or severe medical disorder, and pregnancy.
All subjects were assessed at baseline and monthly for height, weight, body mass index, total fat mass and percentage fat (via bioimpedance measurement), and waist circumference. In addition, fasting blood leptin, prolactin, and antipsychotic serum levels were measured at baseline, week 4, and week 12.
After 12 weeks of treatment, the weight, body mass index (BMI), fat mass and percentage fat, and waist circumference of all of the 174 youth in the study—including 57 on olanzapine, 70 on risperidone, and 47 on quetiapine—increased significantly, Dr. Correll said. The greatest increase in all measures was seen in those youths taking olanzapine, followed by risperidone, then quetiapine, he said. Additionally, nearly 81% of the subjects taking olanzapine experienced extreme weight gain—described as an increase in weight from baseline of 7% or more—compared with 57% and 43% of risperidone and quetiapine subjects, respectively.
All of the study participants experienced significant increases in total cholesterol, LDL cholesterol, and triglycerides. A separate analysis comparing pretreated and antipsychotic-naive patients showed that only the olanzapine-induced cholesterol and triglyceride increases remained significant. “Nevertheless, 19.9% of the youths experienced new-onset dyslipidemia, with similar rates for all three drugs,” Dr. Correll reported.
Multiple regression analysis identified the following correlates of weight gain: weight increase at 4 weeks, baseline-to-end increases in leptin, antipsychotic naive status, olanzapine treatment, and divalproex cotreatment.
With respect to lipids, predictors for both cholesterol increase and for triglyceride increase were a low baseline cholesterol level, antidepressant cotreatment, and a 12-week BMI change. Male gender was a predictor for cholesterol increase only.
“Clearly what we're seeing is that these drugs have an impact on all aspects of body composition, and they lead to dyslipidemia, which further increases the cardiovascular risk profile. We're not suggesting they shouldn't be used because obviously these drugs have an important role, but they should be used carefully, and these side effects should be monitored regularly.
“Pretreatment dietary and lifestyle counseling, particularly among those at highest risk, cannot be overlooked,” Dr. Correll concluded.