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Health Risks Associated with Certain Antipsychotics Warrant Extra Monitoring

Science Update

Some atypical antipsychotics may be more likely than others to cause metabolic and cardiovascular side effects, according to recent analyses using data from the NIMH-funded Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). The two studies were published recently in Schizophrenia Research.

Metabolic changes that lead to weight gain or signs of insulin resistance (e.g., elevated blood glucose or increased serum triglycerides) are known side effects of several antipsychotics. In addition, people with serious mental illnesses (SMIs) like schizophrenia are at higher risk for cardiovascular disease compared to people without SMI. Such risk may be associated with antipsychotic treatment or inadequate treatment of common conditions like high blood pressure. They may also result from lifestyle factors, such as smoking or limited exercise.

Participants of CATIE were randomly assigned to treatment with one of five antipsychotics—olanzapine, risperidone, ziprasidone, quetiapine or perphenazine. All are atypical antipsychotics except the older medication perphenazine. Results from the CATIE trial have been previously reported.

Jonathan Meyer, M.D., of the University of California, San Diego, and colleagues compared baseline data with data collected three months later from 281 CATIE participants. They found that the prevalence of metabolic syndrome increased the most among those on olanzapine (from 35 percent to 44 percent), even if they had preexisting metabolic problems. The prevalence of metabolic syndrome decreased for those on ziprasidone from 38 percent to 30 percent, and remained about the same for risperidone, quetiapine and perphenazine. Those on olanzapine and quetiapine gained the most weight—waist size increased an average 0.7 inches. Waist size of those taking risperidone grew an average 0.4 inches, while those taking ziprasidone showed no change in waist size, and those taking perphenazine lost a small amount of weight on average. Olanzapine also was associated with significant increases in fasting triglycerides, which are a marker of insulin resistance and potential for developing diabetes.

Meyer and colleagues then studied changes in nonfasting triglyceride levels, which are taken when a person has more than one meal in an eight-hour time frame. These levels also may be associated with cardiovascular risk. Using data from 246 different CATIE participants who had provided nonfasting triglyceride baseline and three-month data, they found the greatest increase in levels among those taking quetiapine and olanzapine. Among those taking ziprasidone or perphenazine, there was no change in nonfasting triglyceride levels. Levels for those taking risperidone decreased.

The researchers conclude that the need for frequent and routine monitoring of metabolic and cardiovascular factors is crucial, especially if patients are taking olanzapine and quetiapine, and if they have preexisting metabolic issues.


Meyer JM, Davis VG, Goff DC, McEvoy JP, Nasrallah HA, Davis SM, Rosenheck RA, Daumit GL, Hsiao J, Swartz MS, Stroup TS, Lieberman JA. Change in metabolic syndrome parameters with antipsychotic treatment in the CATIE Schizophrenia trial: Prospective data from phase 1 . Schizophrenia Research. 2008 Apr;101(1-3):273-286.

Meyer JM, Davis VG, McEvoy JP, Goff DC, Nasrallah HA, Davis SM, Daumit GL, Hsiao J, Swartz MS, Stroup TS, Lieberman JA. Impact of antipsychotic treatment on nonfasting triglycerides in the CATIE Schizophrenia trial phase 1.  Schizophrenia Research. 2008 Aug;103(1-3):104-9. Epub 2008 Jun 4.