SAN DIEGO — All atypical antipsychotics carry the same risks for the development of diabetes, according to the Food and Drug Administration, but some experts have a more nuanced view.
Everyone agrees that some atypical antipsychotics are more likely to cause weight gain than are other drugs of the same class. That's enough to make some experts outside the FDA believe that there's also a tiered risk for diabetes in patients who take these medications, Stephen M. Stahl, M.D., said at a psychopharmacology congress sponsored by the Neuroscience Education Institute.
Clozapine (Clozaril) and olanzapine (Zyprexa) cause the most weight gain among atypical antipsychotics. Risperidone (Risperdal) and quetiapine (Seroquel) inhabit a middle ground, and little or no weight gain is seen in patients on ziprasidone (Geodon) or aripiprazole (Abilify).
“As goes weight, so goes risk for diabetes,” said Dr. Stahl of the University of California, San Diego. He has been a consultant for—or received financial support from—the companies that make olanzapine (Eli Lilly & Co.), quetiapine (AstraZeneca), and ziprasidone (Pfizer Inc.).
The divide between the FDA warnings and other expert opinions might be understood as a division between concern about acute hyperglycemic events and the development of diabetes over time, Ramachandiran Cooppan, M.D., said at the same session in a copresentation with Dr. Stahl.
Because there are not enough long-term data to rule out an increased risk for diabetes with all the atypical antipsychotics, and because they seem to have equal risks for causing acute hyperglycemic events, the FDA decided to err on the side of caution and place a blanket warning for diabetes risk on the whole class, said Dr. Cooppan of the Joslin Diabetes Center, Boston.
He has been a speaker or consultant for, or received grants from, the companies that make olanzapine and ziprasidone.
The useful point of the FDA warning is that “there is a myth out there that type 2 diabetes patients can't go into diabetic ketoacidosis. We need to change that,” because up to 40% of people with type 2 diabetes can slip into diabetic ketoacidosis, he noted.
On the other hand, at the time that most case reports of acute hyperglycemic events emerged in patients on atypical antipsychotics, most psychiatrists were not screening patients for impaired glucose tolerance or other diabetes risk factors. “It doesn't take much weight gain to tip you over [into diabetes] if you're genetically predisposed,” Dr. Cooppan said.
The American Diabetes Association guidelines on diabetes risk consider other factors that the FDA did not address, such as changes in lipids, blood pressure, or coagulation, he and Dr. Stahl said.
Comparisons of separate pharmaceutical company-sponsored studies suggest that aripiprazole can significantly reduce triglyceride levels in patients previously treated with an atypical antipsychotic, and that clozapine and olanzapine are associated with the largest elevations in triglyceride levels, Dr. Stahl said. The triglyceride effects of other atypical antipsychotics fall between these two zones.
“We think that there may be a differential risk” for diabetes among atypical antipsychotics, but only time will tell, Dr. Cooppan said.
Dr. Stahl still uses clozapine and olanzapine when needed, despite their potentially higher risk for diabetes.
The important thing is to start balancing the benefits of the drugs with risk differentials when choosing therapy, he explained.
Physicians who prescribe these drugs must be prepared to monitor all severely mentally ill patients for diabetes risk factors regardless of the drug used, he emphasized.
On the front of each chart, put the patient's blood pressure, lipid levels, recent triglyceride level, weight or body mass index, and “maybe even a waist circumference” measurement. “People like us have leverage on our patients to get them to change their lifestyles,” Dr. Stahl said. “None of [this] is very simple, but we should at least try.”
KEVIN FOLEY, RESEARCH/ANGIE RIES, DESIGN