Chronic Hives and Antihistamines

Reviewed by: HU Medical Review Board | Last reviewed: November 2022

Antihistamines are the most common treatment for chronic hives. They work by preventing the action of a body chemical called histamine. For most people with chronic hives, this controls symptoms to some degree.1-2

What is histamine?

Histamine is a chemical that helps with different things in the body. Some of these include:3

  • Helping your stomach make acid
  • Playing a role in inflammation
  • Making your blood vessels wider
  • Affecting the muscles in your intestines and lungs
  • Affecting your heart rate

Histamine is also a key player in the immune response. It helps to protect the body against infection and disease. When histamine is released by the body during an allergic reaction, it is trying to protect you from something that it thinks is harmful. But, in some people, histamine can cause more harm than good. If you have an allergy, your body overreacts to a harmless substance by releasing histamine. This can lead to a range of uncomfortable and potentially dangerous symptoms. Histamine is responsible for the itchy welts that appear on the skin with chronic hives.3

How do antihistamines work?

More than half of people with chronic hives can be treated using 1 or a combination of antihistamines. They reduce the major symptoms of chronic hives, including:1

Antihistamines work by blocking a protein called the H1 receptor. This prevents histamine from activating the protein and leading to symptoms of chronic hives. This is why these drugs are sometimes called H1 blockers or H1 antagonists.2

Examples of antihistamines

There are 2 types of antihistamines: drowsy and non-drowsy. Drowsy versions are older, so they are often called “first-generation.” Non-drowsy options came afterward and are often called “second-generation.” In the United States, many of these are available without a prescription.4

Drowsy antihistamines can enter the brain and block a brain chemical called acetylcholine. This causes drowsiness. Examples of drowsy antihistamines include:1

  • Hydroxyzine (Vistaril®)
  • Diphenhydramine (Benadryl®)
  • Chlorpheniramine (Chlor-Trimeton®)
  • Doxepin (Zonalon®), which is an antidepressant with antihistamine properties

Non-drowsy antihistamines are just as effective as drowsy ones. Doctors often suggest non-drowsy versions first because they do not get into the brain and cause drowsiness. Different people respond better to different non-drowsy antihistamines. Examples of non-drowsy antihistamines include:1

  • Cetirizine (Zyrtec®)
  • Levocetirizine (Xyzal®)
  • Fexofenadine (Allegra®)
  • Loratadine (Claritin®)
  • Desloratadine (Clarinex®)

Many doctors will first suggest a normal dose of cetirizine. If symptoms remain after 2 to 4 weeks, your doctor may increase the dose or change to a different non-drowsy option. If symptoms are still not controlled, they may suggest drowsy versions or other drugs.2,5

What are the possible side effects of antihistamines?

Drowsy antihistamines can cause serious side effects. About 20 percent of people experience significant drowsiness. This can be dangerous and interfere with activities, such as driving a car. Drowsy antihistamines can also affect sleep and learning. Other possible side effects include:6

  • Dry mouth
  • Double or blurry vision
  • Trouble urinating

Drowsy antihistamines can also cause problems when taken with certain other drugs. Children under 2 years old should not take drowsy antihistamines. Older adults should take extra caution when taking them.1

Non-drowsy antihistamines have very few side effects. In most cases, they do not cause problems when taken with other drugs. However, talk to your doctor if you notice any changes in symptoms.2,6

Because of this, some experts recommend that drowsy antihistamines should only be used when non-drowsy options are unavailable. Other experts say healthy people can safely take drowsy antihistamines at bedtime. Combining this with a non-drowsy antihistamine during the day is a possible option. Talk with your doctor about what is right for you.2,6

These are not all the possible side effects of antihistamines. Talk to your doctor about what to expect when taking these drugs. You also should call your doctor if you have any changes that concern you when taking antihistamines.

Things to know about antihistamines

Take antihistamines exactly as your doctor prescribes. Most doctors suggest taking them at the same time every day. Even if symptoms come and go, take your medicine regularly. Taking antihistamines on a regular basis is more effective than taking them as-needed.1

Dosage is important for non-drowsy antihistamines. For some people, a higher dose may control symptoms better without causing side effects. Increasing your dose is often the first thing doctors may try if the standard dose does not work.2,7

Combining antihistamines with asthma drugs may be more effective than antihistamines alone. Your doctor may try this if antihistamines do not control your symptoms. Drugs known as leukotriene receptor antagonists (LTRAs) are often used like this. These include:1,2

  • Montelukast (Singulair®)
  • Zafirlukast (Accolate®)

Before beginning treatment for chronic hives, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs.

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