By: Richard A. Pizzi
While treatment options for severe mental illnesses such as schizophrenia have improved greatly over the past few decades, there is increasing concern among clinicians and researchers that a certain class of antipsychotic medication may have disturbing side effects.
Some of these drugs, called “atypical” or “second generation” antipsychotics (SGAs), have been shown to cause significant weight gain and glucose intolerance in patients, leading the Food and Drug Administration (FDA) to issue a blanket warning on the whole class that associates their use with increased risk of type 2 diabetes.
Link to diabetes causes concern
When studies began to show that troubling side effects like considerable weight gain, glucose intolerance and increased prevalence of type 2 diabetes were not uncommon in patients using SGAs, physicians, scientists and the FDA took notice.
A study appearing the April 2002 issue of American Journal of Psychiatry, found there was an association of diabetes with the use of SGAs. The study used data from a large national sample of patients with a diagnosis of schizophrenia to compare the prevalence of diabetes. Patients treated with SGAs received prescriptions for Clozaril (clozapine), Zyprexa (olanzapine), Risperdal (risperidone) or Seroquel quetiapine).
A total of 22,648 participants received SGAs. Of this group, 5.3 percent received Clozaril, 48.4 percent received Zyrexa, 4.2 percent received Seroquel and 43.7 percent received Risperdal.
The researchers found that “… patients who received [SGAs] were 9 percent more likely to have diabetes than those who received [first-generation antipsychotics], and the prevalence of diabetes was significantly increased for patients who received clozapine, olanzapine, and quetiapine, but not risperidone.”
They added, however, that for patients below 40 years of age, all of the SGAs were associated with a significantly increased prevalence of diabetes.
Diabetes Health first discussed the association between SGA therapy and diabetes incidence in its November 2002 issue (“Oh, the Irony: Does an Insulin Maker’s Schizophrenia Drug Cause Diabetes?”), when it reported the results of a July 2002 study appearing in Pharmacotherapy. According to the journal, Duke University and FDA researchers identified 237 cases of diabetes between January 1994 and May 2001 in people taking Zyprexa. Of this group, 188 were newly diagnosed cases. Of the total, 80 people developed ketosis, 41 had glucose levels of 1,000 mg/dl or higher, and there were 15 deaths. Nearly three-quarters of the cases began within six months of starting treatment with Zyprexa.
Both Clozaril and Zyprexa are also associated with the greatest increases in total cholesterol and triglycerides. The SGA Risperdal may also have an increased risk of high blood glucose, according to an August 2004 FDA warning.
Other SGAs have a mixed, though somewhat better, record on risk factors for type 2 diabetes. Geodon (ziprasidone) is relatively new, but early studies suggest that it is weight-neutral and does not appear to increase the risk of type 2 diabetes.
Abilify (aripiprazole) is a very new SGA, but clinical trials indicate that, like Geodon, it has a better cardiovascular profile than the other SGAs and does not show an increased risk for diabetes.
According to a Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes, convened by the American Diabetes Association (ADA), most of the available data on the prevalence of obesity and type 2 diabetes in SGA users comes from studies of patients with schizophrenia. In defense of their products, the manufacturers of the various medications claim that, regardless of drugs used, these patients tend to have higher rates of obesity and type 2 diabetes than does the general population. The prevalence of obesity and diabetes in schizophrenics and people with affective disorders is almost twice as high as that of people who do not have such illnesses. Forty-two percent of schizophrenia patients are obese, and 75 percent smoke tobacco, which contributes to a death rate from cardiovascular disease that is two times the national average.
In all, the average life expectancy of a person with schizophrenia is 20 percent shorter than that of the average American without mental illness.
Weighing the benefits and the risks of SGAs
These facts notwithstanding, the FDA and the participants in the ADA conference recognize that there is an increased prevalence of obesity, impaired glucose tolerance and type 2 diabetes in people treated with SGAs. This does not mean, however, that SGAs should not be used in the treatment of psychiatric illness. While this class of drugs may produce metabolic side effects, they also offer tangible benefits to people suffering from mental illness.
According to the October 2004 Journal of Clinical Psychopharmacology, one 2003 poll of psychiatrists found that 43 percent believed diabetes to be an “acceptable risk factor” in the use of SGAs. These clinicians thought that eliminating the psychotic features of schizophrenia, such as hallucinations and delusions, was of more immediate importance than the risk of developing type 2 diabetes.
The ADA conference concluded, in line with most of the research, that clinicians should choose antipsychotic medications based primarily upon treatment efficacy but should also take the risks of obesity, metabolic syndrome and type 2 diabetes into consideration. Of utmost importance is the need to screen patients for impaired glucose tolerance and other diabetes risk factors and to continue monitoring these factors throughout treatment.
As one physician at a recent psychopharmacology conference suggested, it appears that psychiatrists must now become “de facto endocrinologists.”
Two generations of antipsychotic meds
Although antipsychotic medications were first developed about 50 years ago, SGAs rose to prominence in the 1990s, as psychiatrists searched for medications that would effectively treat severe psychotic illnesses and other psychiatric conditions without the distressing and often disabling side effects common to other antipsychotic drugs.
The medications originally produced for treatment of psychotic conditions are known as “first generation” antipsychotics (FGAs). These medications are still available but are not as widely used as SGAs. The names of some of the more popular FGAs, like Thorazine (chlorpromazine) and Haldol (haloperidol), are instantly recognizable. Like the newer SGAs, the FGAs successfully treat symptoms of psychosis such as hallucinations and delusions. Because they are so effective and better tolerated than FGAs, psychiatrists tend to prescribe SGAs before other drugs and, given the nature of the illness they are treating, continue their use for extended periods of time.