Unusual combo reduces health risk from atypical antipsychotic

The consequences of developing diabetes from taking antipsychotics are dire, as they occasionally cause life-threatening conditions and sometimes even death.

Members of Shuji Kaneko's lab at Kyoto University looked for potential antidotes on the US FDA's Adverse Event Reporting (FAERS) system, which is the largest database of self-reported adverse side effects. "We found that patients who had coincidentally been prescribed vitamin D with quetiapine were less likely to have hyperglycaemia," says Kaneko. "It's unusual for vitamin D to be prescribed with quetiapine because it is typically prescribed to treat osteoporosis; in fact, there were only 1232 cases in the world where vitamin D was prescribed with quetiapine. Data mining proved helpful in locating these cases."

The team confirmed this finding with further tests on mice; the group of mice that was fed vitamin D along with quetiapine had significantly lower levels of blood sugar than those that took only quetiapine.

"Interestingly, vitamin D on its own doesn't lower diabetes risk, but it certainly defends against the insulin-lowering effects of quetiapine," elaborates lead author Takuya Nagashima. "We clarified the molecular mechanisms of how quetiapine causes hyperglycaemia using datasets in a genomics data repository. Through this we found that quetiapine reduces the amount of a key enzyme called PI3K that gets produced. Vitamin D stops quetiapine from lowering PI3K production."

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