If you’re taking a single prescription drug, it’s not so hard to know which side effects to look out for.

But if you’re taking more than one, there are potential side effects for each drug to keep track of, plus a possibility the drugs will interact to create problems on a whole other level.

It’s not a trivial problem. Nearly a third of adult Americans take five or more different medications a week, according to an estimate cited by the Institute of Medicine a few years back.

Some interactions are predictable because scientists and doctors understand the paths the medicines take inside the body. Others, though, are discovered only after the medicines are on the market and doctors notice trouble.

Yet so few drugs are studied in combination with other drugs that there’s a real possibility that something could go wrong for quite a while without anyone catching on to a pattern.

Some academic researchers who are looking for new ways to crack the problem just published an intriguing paper that found an interaction nobody ever expected.

A combination of the antidepressant Paxil (or paroxetine, generically) and cholesterol-fighter Pravachol (or pravastatin) was associated with a big increase in blood sugar. Each of those medicines is prescribed to more than 15 million Americans each year.

The connection turned up when the researchers combed nearly 13,000 reports of adverse reactions made to the Food and Drug Administration looking for diabetes-related complications that might be related to pairs of drugs.

To figure out how big a problem it might be for patients taking Paxil and Pravachol, the researchers combed electronic medical records for hospitals affiliated with Stanford, Vanderbilt and Harvard to find people who had been prescribed both medicines.

They dug into the data for 239 people who fit the bill and found the combination led to blood sugar increases of about 19 milligrams per deciliter of blood, overall, and 48 milligrams per deciliter in diabetics. (Normal fasting blood sugar is less than 100 milligrams per deciliter or lower.)

The results were just published online by the journal Clinical Pharmacology & Therapeutics.

Lead author Nicholas Tatonetti, a doctoral candidate in Stanford’s biomedical informatics program, tells Shots the change in blood sugar could be enough to push someone over the line into diabetes territory or to complicate treatment for somebody already diagnosed with diabetes.

Intriguingly, there was no indication that other antidepressants like Paxil or statins other than Pravachol combined for the same effect.

To be sure, the paper stresses that the “clinical significance of our finding is not clear.” A mechanism to explain the effect isn’t obvious, and there could be some unknown variable that could be confounding the results.

Still, Tatonetti is confident the paper helps prove the principle that mining adverse event reports can yield significant and unexpected results when it comes to drug combinations.

Did it take some ultraslick supercomputer to do the job? Nope. Nicholas says his MacBook Pro was up to the task. It’s just a matter of training the right software algorithm to look for specific side effects and turning it loose, he says. The analysis only takes a few minutes.

He believes the technique can be used to find “hidden interactions that are going on all the time…from data we already have.”

Bonus Checker: To look for known drug interactions, try this online checker at Drugs.com