Metabolic side effects of antipsychotics are known, but rarely monitored

Psychiatrists are doing a “modest” job of monitoring for weight gain, diabetes and other metabolic problems that may result from use of the newer antipsychotics for schizophrenia, researchers say.

Nearly all of the 258 members of the American Psychiatric Association in Georgia, Ohio and Iowa responding to a survey said they considered metabolic side effects serious or very serious, say researchers from the Medical College of Georgia, University of Iowa and Northcoast Behavioral Healthcare in Ohio.

However monitoring for these problems – including getting baseline data on personal and family health history as well as baseline and regular checks of height and body weight, waist circumference, blood pressure, fasting blood glucose and lipid levels – largely goes undone, researchers say of findings being presented during the 10th International Congress on Schizophrenia Research April 2-6 in Savannah, Ga.

“What we have found is that metabolic problems often associated with these drugs are a substantial concern and that clinicians are slowly beginning to change their practice to reflect that concern,” said Dr. Peter F. Buckley, lead investigator on the study and chair of the MCG Department of Psychiatry and Health Behavior.

Antipsychotics, such as clozapine and risperidone, which have come on the market in the last 10-15 years are touted for an improved ability to treat the delusions and hallucinations of schizophrenia without damaging muscle control, Dr. Buckley says. Parkinson-like tremors have been associated with older antipsychotics.

“These newer drugs are definitely more effective, they are just not without their own side effects,” Dr. Buckley says. “Some of those side effects fit unfortunately well with what’s happening in the world and America with rampant problems with obesity and type 2 diabetes.”

Groups such as the American Diabetes Association, the American Psychiatric Association and the American Association for Clinical Endocrinologists, have weighed in, making recommendations for evaluating and monitoring adverse metabolic effects. However, much like the current study, a 2004 phone survey of 300 psychiatrists commissioned by a pharmaceutical company showed while most were aware of metabolic consequences many had not incorporated recommendations for dealing with them into their practice.

“We still have a way to go,” says Dr. Buckley, who had just met with a young woman with schizophrenia already struggling with her weight. “I was telling her she needs a drug for her illness and that, unfortunately, there is also a risk that this drug will make her gain weight. She said she didn’t want to take it. I said you really don’t have a choice to take nothing. It’s awful having to present people with such difficult choices, especially when they’re already stressed dealing with mental problems,” he says.

Noncompliance has long been a problem for schizophrenics, because of movement problems associated with older drugs, and because many patients don’t realize they are ill, he says. The newer class of drugs work effectively to silence the over-communication in the brain that causes hallucinations, the hallmark of schizophrenia, by dampening the action of the neurotransmitter dopamine. Somehow in that process of altering brain chemistry, they also make people hungrier and likely alter metabolism, Dr. Buckley says.

Whether genetics will one day help a physician identify which drugs are most likely to have this impact is the focus of another federally funded collaborative study with the University of Iowa being presented at the schizophrenia meeting. “In this study,” says Buckley, “we discovered that a patient’s genetic make-up of their serotonin receptors can predict whether a patient will gain weight or not during treatment with clozapine.”

Another study being presented seeks to give physicians and patients information on which of the newer drugs are best for cognition.

Impaired cognition – problems with the ability to think, learn and remember – has been recognized as a symptom of schizophrenia for more than a century, says Dr. Alvin V. Terry Jr., pharmacist and pharmacologist at the University of Georgia and MCG.

While antipsychotics weren’t developed with cognition in mind, the older ones, called typical antipsychotics, are known to further impede cognition while the newer atypicals are believed to improve it.

Dr. Terry is principal investigator on a $1.1 million grant from the National Institutes of Health examining the impact of long-term use of atypicals.

“We are still finding in most of our cognition studies that the older drugs are worse than the newer drugs, however within the newer drugs, some are better than others,” says Dr. Terry. “Part of my goal is to differentiate the new drugs.”

He started his studies in healthy animal models to first determine the drugs’ impact on cognition, with behavioral tests as well as to analyze the drugs’ impact on different circuitry involved in memory function.

The early findings he’s presenting in Savannah show a modest reduction in this circuitry with long-term use of risperidone or Risperdal®. “What we are finding in this study is that risperidone actually decreases alpha 7 nicotinic receptors in the hippocampus and cortex, big areas for memory,” says Dr. Terry.

As an expert in drug function, he notes that it’s probably impossible to develop a drug that has only positive actions without side effects. But he hopes his research, along with studies such as Dr. Buckley’s, will enable patients to get the most effective drug with the least side effects.