Antipsychotics Rapidly Boost Cardiovascular Risk

Fran Lowry

February 16, 2011

February 16, 2011 — The risk for cardiovascular disease in people with psychosis increases after their first exposure to antipsychotic drugs, according to new research published online February 7 in the Archives of General Psychiatry.

"This change in risk is evident early in the course of treatment, within several weeks of continuous use, but may continue over years," study investigator Debra L. Foley, PhD, of the University of Melbourne in Australia, told Medscape Medical News.

Schizophrenia is associated with a reduced life expectancy, and most early deaths are due to cardiovascular disease.

"We wanted to review what was known about the role of antipsychotic drugs in altering early risk factors for cardiovascular disease," Dr. Foley explained.

Dr. Foley and coauthor Katherine I. Morley, PhD, from the Wellcome Trust Sanger Institute, Hinxton, United Kingdom, undertook a systematic review of baseline and posttreatment risk factors for cardiovascular disease in patients receiving drug treatment for psychosis for the first time. The analysis included 25 studies published between January 1990 and June 2010.

All subjects were experiencing their first treated episode of psychosis and were either antipsychotic naive or had been exposed to antipsychotics for between 9 days and 16 weeks. Eight of the studies also included controls that were recruited from hospital staff, universities, the general community, and a workplace-screening program.

Rapid Metabolic Change

The investigators found that changes in weight, body mass index, and waist circumference were evident in the patients receiving the antipsychotic drugs after 1 month.

After 6 weeks, there was a significant increase in interleukin 12. After 10 weeks, there was a significant increase in subcutaneous and intra-abdominal fat, a 3-fold increase in leptin level, and a significant increase in total and low-density lipoprotein cholesterol, triglyceride, and nonfasting glucose levels.

After 6 to 12 months, total body weight increased by 10% to 12%, and most of this increase occurred in the first 6 months. Between 36% and 42% of patients were overweight or obese at baseline, the same as in the broader community, but after 6 months, 58% to 71% were overweight or obese, the study authors report.

Patients who continued to take antipsychotic medication also continued to steadily gain weight.

After 1 year, the average weight gain reported with olanzapine was 11 to 17 kg; amisulperide, 10 kg; clozapine, 10 kg; quetiapine, 10 kg; risperidone, 8 to 9 kg, haloperidol, 4 to 11 kg; chlorpromazine, 6 kg; ziprasidone, 5 kg; and perphenazine, 1 kg.

All patients treated with antipsychotics need to be monitored for any clinically significant change in risk factors for heart disease.

"Early identification of these changes may minimize risks if coupled with appropriate interventions," Dr. Foley said.

Her hope is that the message from this study will compel health services for patients who must be taking these drugs to monitor them regularly for early changes in risk factors for cardiovascular disease.

"Any changes in risk factors for cardiovascular disease should be treated following recommended guidelines. Doctors and their patients who are taking these drugs must work together to minimize risk," she said.

Drugs or Poor Lifestyle?

Commenting on this study for Medscape Medical News, J. Steven Lamberti, MD, professor of psychiatry at the University of Rochester School of Medicine in New York, said schizophrenia itself is associated with metabolic disturbances, either directly or indirectly through poor lifestyle habits. It has also been previously shown that antipsychotic drugs have metabolic side effects.

However, he added, it has been a challenge to tease out the two. This study gives a snapshot of how people look before they received medication and after, so it helps us sort out where these metabolic problems are coming from," he noted.

People with psychosis will most likely have many modifiable risk factors for heart disease, such as poor diet, lack of exercise, and higher rates of cigarette smoking. Plus, they must take antipsychotic medication, a risk factor that is not modifiable.

"All of these risk factors play together and are contributing to the increased mortality that we see in people with schizophrenia. This paper is telling us that we need to pay attention to these risk factors at the very beginning of treatment, that when somebody is getting an antipsychotic drug for the first time, we can expect the risk for cardiovascular disease is going to increase shortly after the very first exposure, and so we need to do a better job of prevention. We need to intervene earlier. That's really the take-home message of this paper," said Dr. Lamberti.

Dr. Foley, Dr. Morley, and Dr. Lamberti have disclosed no relevant financial relationships.

Arch Gen Psychiatry. Published online February 7, 2011.

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