Vitamin D Reduces Hyperglycemia Risk Associated With Atypical Antipsychotics

Vitamin D may help reduce the risk of diabetes side effects associated with atypical antipsychotics, according to a recent study published in Scientific Reports.

Atypical antipsychotics have long been associated with an increased risk of hyperglycemia—which can lead to new-onset diabetes, diabetic ketoacidosis, coma, and even death. Some proposed mechanisms for this effect include weight gain, decreased insulin secretion from pancreatic beta cells, and insulin resistance.

To determine whether there were any medications that could decrease this likelihood of hyperglycemia, researchers analyzed the FDA’s Adverse Event Reporting (FAERS) system—a database that logs self-reported adverse effects or medication errors submitted by patients. By cross-referencing atypical antipsychotics and hyperglycemia, the study authors found that patients who had been simultaneously prescribed to take vitamin D and quetiapine were somehow less likely to have hyperglycemia.

Subsequent tests on mice produced similar results; mice that were given vitamin D and quetiapine turned out to have significantly lower levels of blood sugar than those that were given only quetiapine. Lead author Takuya Nagashima explained this effect as vitamin D inhibiting quetiapine from reducing a key enzyme necessary for hyperglycemia in the body. Among common atypical antipsychotics, the strongest association (odds ratio [OR] >20) was observed for quetiapine and olanzapine, while an intermediate association (5&thinsp;<&thinsp;OR&thinsp;<&thinsp;20) was observed for risperidone, aripiprazole, and ziprasidone.

Based on the results, the authors propose a “novel vitamin D/antipsychotic combination pharmacotherapy in which vitamin D can efficaciously safeguard against antipsychotic-induced hyperglycemia accompanied by insulin resistance.”

The study, conducted by Kyoto University researchers, may offer important cost-benefit implications by pinpointing what could reduce potentially pricey side effects. Having to use additional drugs (such as metformin) to treat antipsychotic-induced hyperglycemia not only “poses a risk of an added side effect burden, but increased costs on someone receiving the antipsychotic,” said Lindsay DeVane, PharmD, a professor at the Medical University of South Carolina. These additional treatments are necessary because antipsychotic-induced hyperglycemia is complex and difficult to treat with a single-drug therapy. Adding vitamin D would be a relatively small price to pay in comparison to adjunct diabetic treatment.

“Vitamin D would cost the patient pennies in the grand scheme of things. It never hurt anyone to take extra vitamins, and if doing so could help reduce the risk of hyperglycemia in just one case—that’d be a success,” said Craig Liljeberg, PharmD, a pharmacist at Northern Nevada Adult Mental Health Services.

The study was also important in helping bring the utilization of computerized information databases to the forefront of medical studies.

"Databases like FAERS aren't just for making drug regulations; they have so much potential for side-effect relief using pre-existing drugs," lead author Shuji Kaneko said in a statement. "There's a lot we can hope for from reverse translational research like this."