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Atypical Antipsychotics No Better Than Older Antipsychotics in Treatment Trial

Atypical Antipsychotics No Better Than Older Antipsychotics in Treatment Trial

Recent headlines point to research that suggests atypical antipsychotics are no more effective than their older counterparts in the treatment of children and adolescents with schizophrenia and psychosis.

According to the New York Times,1 risperidone and olanzapine have been increasingly prescribed for children in the past 15 years. Risperidone has received FDA approval for use in children as young as 13 years with schizophrenia. Olanzapine has not been approved for this population. The Times cited a study by Sikich and colleagues2 that called current prescribing practices into question.

That study included 119 patients aged 8 to 19 years with psychotic symptoms. Participants received risperidone, olanzapine, or the first-generation antipsychotic molindone for 8 weeks. Of the sample, 34% who received olanzapine, 46% who received risperidone, and 50% who received molindone showed significant improvement at study completion. These results suggest that molindone is as effective as newer antipsychotic medications.

Those who took olanzapine or risperidone gained significant weight, possibly putting them at risk for heart disease and diabetes. The study sponsor, NIMH, halted recruitment to the olanzapine arm because of “weight gain and the resulting increase in cholesterol and glucose levels” among participants. Although typical and atypical antipsychotics block dopamine receptors in the brain, the newer drugs also interact with serotonin receptors and, unlike older drugs, cause fewer muscle adverse effects. There were more reported cases of restlessness with molindone, even though participants treated with this drug were also required to take benztropine to decrease muscle cramps and stiffness.

Another recent study also found weight gain to be significant among those treated with the atypicals. Fraguas and colleagues3 treated 66 children and adolescents for 6 months with risperidone (n = 22), olanzapine (n = 20), or quetiapine (n = 24). Over half the enrolled patients had schizophrenia or other psychoses.

After 6 months, body mass index scores increased significantly in patients who received olanzapine and risperidone; half the patients showed significant weight gain. The number of patients at risk for hypertension, impaired vascular function, dyslipidemia, atheroma, type 2 diabetes, systemic inflammation, and oxidative stress increased from 11 to 25 (P = .018); this increase was significant only in the olanzapine group. The authors urged careful monitoring for weight gain, dyslipidemia, glucose intolerance, and hypertension and recommended clinical intervention to reduce the risk of these sequelae.



1. Carey B. Study of newer antipsychotics finds risks for youths. New York Times. September 15, 2008:A17. http://www.nytimes. com/2008/09/15/health/research/15drug.html. Accessed October 13, 2008.
2. Sikich L, Frazier JA, McClellan J, et al. Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early onset schizophrenia spectrum disorders (TEOSS) study. Am J Psychiatry. 2008 Sept 5; [Epub ahead of print].
3. Fraguas D, Merchan-Naranjo J, Laita P, et al. Metabolic and hormonal side effects in children and adolescents treated with second-generation antipsychotics. J Clin Psychiatry. 2008; 69:1166-1175.
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