Which allergy medication works the best? It’s complicated.

But here’s our best advice.

This post has been updated. It was originally published on April 19, 2020.

We may not know much about allergies, but gosh darn it do we have some great drugs for them. In the United States, the allergy medication aisle in a typical pharmacy is a veritable Baskin Robbins of drug options. Nasal sprays. 24-hour non-drowsy pills. Sleep-inducing, decongesting, grape-flavored serums. We’ve got it all.

But how do you choose? Ask your friends, and you’ll probably get five different recommendations on which is absolutely the best. And unfortunately for you, they’re all correct.

“Figuring out which medications are right for you is like trying to navigate a complex roadmap for a long road trip,” says Sarena Sawlani, Medical Director at Chicago Allergy and Asthma. “There usually isn’t a ‘one size fits all’ approach.” She explains that different medications—and combinations of them—will suit individuals differently, and the results depend a lot on the situation. Is the user in an area with a new potential allergen? Do they take other drugs that alter their immune system?

[Related: These are the most common allergies (and the deadliest.)]

Even if the context seems pretty neutral, Sawlani says that “we are all wired a bit differently, and so a personalized approach to finding the right medications for each individual is important. The medications may work through the same mechanisms, but we all may respond differently depending on what’s causing the symptoms and how our bodies handle them.”

Different medications work for different people—we’re just not sure why

Antihistamines aren’t all created equal—but it’s pretty close. The pills labeled as such in the allergy aisle all work on the same basic principle.

Allergy symptoms are caused by your body reacting to irritants like pollen or pet dander and releasing large quantities of a chemical called histamine. Histamine expands your blood vessels and increases mucus production, among other things, by attaching to receptors on the cells in your nose and sinuses. Antihistamines work because they look kind of like histamine, and can therefore bind to histamine receptors—except better. They’re designed to have a very high affinity for histamine receptors, such that they compete with histamine for the sites. The difference is that antihistamines don’t activate the receptor, and thus block the effects.

The only real differences between pills like Allegra (fexofenadine), Zyrtec (cetirizine), and Claritin (loratadine) are how the body metabolizes them. Loratadine gets processed a lot by your liver, whereas cetirizine and fexofenadine don’t as much. This shouldn’t have an effect on how well they bind to histamine receptors, but depending on your personal metabolism and liver, it may change the side effects. We don’t know much about what these metabolites might affect or how exactly they alter the overall function of the drug. We just know that some people won’t react the same way to the same drug, so if the metabolites of loratadine don’t sit well with you, another brand may be better.

Some of the antihistamines also work a bit better on rashes and other skin symptoms. Cetirizine and fexofenadine tend to accumulate more in your skin tissue, so they have a slightly higher impact on the histamine receptors there than loratadine does. But again—your mileage may vary.

Nasal sprays definitely seem to work better for allergy relief

The one thing that holds clear across all the drug options is that corticosteroids seem to work the best. Corticosteroids are the active ingredient in those nasal sprays you see, and though they take longer to become fully effective, they control symptoms better in the long term. That’s because they don’t just prevent histamine from binding to its receptor—they prevent inflammatory cells from starting to react even before histamines can enter the picture.

[Related: Local honey might help your allergies—but only if you believe it will.]

This system works best after the steroids have built up a bit in your system and have had longer to modulate your immune response, so it’s best to start taking them a few weeks before allergy season begins.

Pro tip: try combining an antihistamine and a corticosteroid. Since they work through slightly different mechanisms, the combination could help get rid of those last few pesky symptoms. Though as Sawlani noted, different combinations will work better for some people and not for others, so expect some trial and error.

What you think will work for your symptoms probably will

It’s also important to point out here that the placebo effect is quite strong for all things allergy-related. Studies of allergy treatments all have to contend with this issue, and one notable study found that the placebo effect holds even if you tell people they’re taking a placebo. Their symptoms will decrease anyway.

This doesn’t mean that allergies are all in your head—it just means your head is more powerful than you think. So if your current allergy cocktail seems useless, changing brands or delivery methods might help simply by making you feel like you’re taking action.