Clinical and Research News
Schizophrenia Drugs Differ Considerably In Metabolic-Syndrome Risk
Psychiatric News
Volume 41 Number 8 page 39-39

In the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, in which patients were randomly assigned to receive olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone, CATIE's phase 1 results showed that patients in the olanzapine group gained more weight than patients in any other group, with an average weight gain of two pounds a month.

Further, a larger proportion of patients in the olanzapine group than in the other groups gained 7 percent or more of their baseline body weight.

"Olanzapine had effects consistent with the potential development of the metabolic syndrome and was associated with greater increases in glycosylated hemoglobin, total cholesterol, and triglycerides after randomization than the other study drugs, even after adjustment for the duration of treatment," the CATIE authors wrote.

The initial report from the CATIE study appeared in the September 22, 2005, New England Journal of Medicine.

A 2004 study by Newcomer and Henry Nasrallah, M.D., cited one meta-analysis of antipsychotic use and weight gain that found therapy with clozapine and olanzapine was associated with an average increase in body weight of 9.9 pounds and 9.2 pounds, respectively, while those treated with risperidone or ziprasidone gained an average of 4.7 and 0.9 pounds, respectively. (That meta-analysis, "Antipsychotic-Induced Weight Gain: A Comprehensive Research Synthesis," appeared in the November 1999 American Journal of Psychiatry.

Clozapine and olanzapine also appear to carry the greatest risk of increased triglyceride and lipid levels, hyperglycemia, and onset of type II diabetes, Newcomer and Nasrallah wrote.

Their report, "Atypical Antipsychotics and Metabolic Dysregulation: Evaluating the Risk/Benefit Equation and Improving the Standard of Care," appeared in the October 2004 Journal of Clinical Psychopharmacology, supplement 1. It was supported by a grant from Pfizer Pharmaceuticals, manufacturer of ziprasidone.

William Carpenter, M.D., director of the Maryland Psychiatric Research Center, noted that clozapine is the only antipsychotic drug that has FDA approval for the treatment of refractory schizophrenia. "Many studies fail to document superior effects of second-generation antipsychotics, and it is not clear that olanzapine is superior in general or even if some individuals are uniquely responsive," he said.

But Ron Landbloom, M.D., associate medical director for neuroscience at Eli Lilly and Co., which manufactures olanzapine, noted that in the CATIE study olanzapine was associated with a greater reduction in psychopathology, longer duration of successful treatment, and lower rate of hospitalizations for an exacerbation of schizophrenia.

"All the atypicals have been associated with metabolic changes," he said. "It comes down to a risk-benefit discussion that physicians must have with all patients about what is the optimal treatment."

Landbloom also said Lilly supports educational efforts aimed at psychiatrists and endocrinologists about identifying and monitoring metabolic syndrome, and advocates a "complete wellness" approach to treatment aimed at the mental and physical health of people with mental illness.

More information on this approach is posted online at<www.completewellnessapproach.com>.

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