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