FDA to Require Diabetes Warning On Antipsychotics

“The FDA was in a very difficult position,” Newcomer noted. If the agency had done nothing, it would have been accused of being nonresponsive. If the FDA ordered selective labeling—only certain drugs within the class—then the agency “would really have been on the spot to justify that position.”

In ordering warnings across the entire class of atypicals, however, Newcomer believes the agency may have been trying for the middle ground—not wanting to single out one medication. Yet by avoiding the weight issue, he said, the FDA appears to have caught the ire of a number of specialists familiar with the issue.

“Clearly, the NIH [and] the [American Diabetes Association] say that weight gain is a major risk factor for diabetes mellitus and that it should be watched. Yet there is little mention of it in the FDA warning,” Newcomer said.

In addition, he maintains that the warning could have been more specific on what physicians should do if a patient develops serious diabetic complications, as well as how patients taking atypical antipsychotic medications should be monitored to catch any impairment in glucose control early. Newcomer also believes that “the FDA could have identified that there are differences in short- and long-term weight gain among the individual medications that are already detailed in the package inserts and should be considered as part of monitoring and treatment decisions.”

In its letter to Lilly, the FDA “acknowledge[s] that additional labeling changes may be required as new information becomes available. Areas that require additional research include, but are not limited to, identification of subpopulations at greatest risk for diabetes mellitus adverse events, exploration of the relative risk for diabetes mellitus adverse events among the different antipsychotics, and evaluation of potential mechanisms of action.”

Each of the companies involved continues to pursue these and other research questions in an attempt to resolve the issue, and most of the companies told Psychiatric News that they will review the requested labeling changes and work out final language with the FDA.

Endocrinologists are intimately involved in attempting to answer key questions as well. The American Diabetes Association (ADA) has scheduled a November 19 consensus development conference to address the relationship between antipsychotic medications and diabetes.

Newcomer is a member of the ADA consensus panel’s planning committee. (He noted that the final consensus committee will be made up of endocrinologists and senior psychiatrists who—like himself—have no research or financial interest in the companies that make the medications at issue.) The ADA conference is currently targeted at primary care physicians and endocrinologists, Newcomer said, who have not yet heard much about the diabetes problems that psychiatric patients are encountering. However, the results of the conference will have obvious relevance beyond those fields.

APA is also working on the issue, having established an antipsychotics and diabetes subcommittee under the Corresponding Committee on Research on Psychiatric Treatments. Newcomer also is on this subcommittee.

“What remains to be seen is whether the ADA comes out with a consensus statement that is in line with or different from the FDA’s language,” Newcomer said. “Will there be any clarity to the monitoring and treatment recommendations? APA’s subcommittee will watch this very closely and will be in a position to add to or clarify the ADA statement, so that we get the most accurate and complete information out in a timely manner.”