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Medications That May Cause Headache as a Side Effect

woman grabbing her head in pain

Headaches are very common. Most people experience them multiple times in their lifetime. Headache pain can be sharp, throbbing, dull, constant, or episodic. The location, severity, and frequency of headaches can vary. There are many types of headaches with different causes. A relatively lesser-known cause of headaches is a side effect of an over-the-counter or prescription medicine. Please continue reading to find out which medications can cause a headache as an adverse reaction. 

What are the different types of headaches?

The International Headache Society classifies headaches into primary and secondary headache disorders. 

Primary headache disorders are conditions in which the headache is not triggered by any type of illness, allergy, or infection. In other words, the pain in your head is the condition, and there is no underlying problem. The cause of primary headaches are complicated, but it is believed that genetics can be a factor, making some more prone than others. Changes in blood flow and chemical activity in your brain due to muscle activity in your head and neck can also contribute to headaches. Even though primary headaches are not symptoms of an underlying problem, lifestyle factors can sometimes trigger them. The good news is that you can take control of these triggers; examples include certain foods, especially processed, nitrate-containing deli meats, alcohol, stress, changes in sleep habits, lack of sleep, and prolonged poor postures. Some of the most common types of primary headaches include migraine headaches, cluster headaches, tension headaches (episodic tension-type headaches and other subtypes in this group), and another type of primary headache, also classified as a chronic daily headache due to its long-lasting effect. 

Secondary headaches occur due to an underlying health condition. Though rare, it can be a sign of a brain tumor, aneurysm, head or neck injury, or meningitis (brain inflammation caused by bacterial or viral infections). They can start suddenly and cause severe pain. A secondary headache is much more serious than a primary headache because it is a warning sign of a severe health problem.

What could be the cause of chronic daily headaches?

Chronic daily headaches are not a specific type of headache. Various factors can cause severe headaches on a daily basis. Rather, chronic headaches are any headache that occurs 15 days or more a month for three months or longer. 

Chronic daily headaches can be short-lasting or long-lasting (at least four hours). There are five types of chronic daily headaches: chronic migraines, chronic tension-type headaches, new daily persistent headaches, chronic post-traumatic headaches, and hemicrania continua (a continuous headache on one side of the head). 

Why do certain medications cause headaches? 

Different medications with different mechanisms can cause headaches for people who use them short-term, long-term, or even after drug discontinuation. There are not many studies on headaches as adverse reactions to medications. However, in most cases, when it comes to drug-induced headaches, there are two main causes of this adverse drug reaction (ADR): vasodilation (widening of the blood vessels) and an increase in intracranial pressure.

What is a medication overuse headache?

You may be surprised to learn that medications used to treat headaches can cause headaches. These are called medication overuse headaches (MOH), previously referred to as analgesic rebound headaches. 

MOH can be debilitating as the headache sufferers take more than the recommended dosage to alleviate their headache pain which, in turn, causes daily or near-daily severe headaches. When someone uses pain medicines several times a week to relieve headaches, a medication overuse headache can happen. Once the medication wears off, the pain returns, prompting headache sufferers to take more pain medicine. This leads to a vicious cycle of having severe headaches and taking increasingly more headache medication, hoping for relief. Consequently, the headache returns more severe and frequent. 

To prevent medication overuse headaches, you should take prescription medications exactly as prescribed by your family medicine doctor and avoid self-treating with non-prescription medicines. For over-the-counter pain relief, do not use more than the recommended dose to treat chronic headaches. Consult your family or internal medicine doctor if you have a headache history or your headache becomes more frequent and severe. A referral to a headache specialist may be beneficial for you.

If your doctor suspects a rebound headache, they may ask you to maintain a headache diary. Discontinuation of overused medication is the treatment of choice for this type of headache. Your doctor will instruct you either to stop the medication abruptly or taper down slowly.  Below are some of the common medicines that can cause rebound headaches:

Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs)

Over-the-counter pain medicines such as acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs like aspirin, ibuprofen (Advil, Motrin), and naproxen (Aleve) can cause rebound headaches. The risk is especially high if you take more than the recommended daily dose. Medication misuse headache is common with the combination of non-prescription medicine containing acetaminophen, aspirin, and caffeine. This headache pattern is believed to be in part due to caffeine withdrawal symptoms.

Prescription pain medicines

Various migraine medications, including triptans (Zomig, Imitrex, Maxalt, Amerge, Frova, Relpax, Axert, and others), have been linked to medication overuse headaches. In addition, prescription pain medicines like opioids (for example, combinations of acetaminophen and codeine) have a high risk of causing rebound headaches.

Which medications can cause headaches as a side effect?

Some medicines that can cause headaches as a side effect are described below.

Birth control pills 

Headache is a frequent side effect of hormone therapy such as birth control pills, patches, shots, rings, implants, and hormonal intrauterine devices (IUDs). In fact, many women discontinue the use of birth control pills and other types of hormone therapy because of increasing headache frequency.

Blood pressure medications

Blood pressure medicines called calcium channel blockers work by causing vasodilation (widening of the blood vessels). This effect can lead to a drug-induced headache. Headaches induced by blood pressure medicines are more likely at higher doses.


Nitrates (nitroglycerine, isosorbide, and others) are medications used to treat chest pain (angina) in people with heart disease. These drugs work by promoting blood flow to the heart by widening the blood vessels. Some people develop a mild to moderate nitroglycerin-induced headache immediately (within an hour of taking a dose). Others develop a severe migraine-like headache 3-6 hours after taking a nitrate dose. Nausea, vomiting, and sensitivity to light are some other possible side effects. Don’t stop taking nitroglycerin if you develop a headache, as it can lead to serious consequences. You should talk to your doctor if the headaches become severe and bothersome. Also, keep in mind that some headache medicines are not safe for those with heart diseases. 

Erectile dysfunction drugs

Medications used to treat erectile dysfunction can also cause headaches as a side effect. Approximately 1 in 4 people who are prescribed sildenafil (Viagra) experience headaches. For those with a history of cluster headaches, it may be beneficial to consider a lower dose of other drugs of the same class.

What is the treatment for headaches caused by adverse drug reactions?

Many medications can induce headaches as an unwanted side effect or adverse drug reaction. However, establishing a direct link between a medication and a headache may not always be possible. 

Headache induced by medications can be treated by:

  • Reducing the dose of the offending medicine.
  • Drug discontinuation.
  • Use of preventive medications for headaches.
  • Use of other medications to treat headaches.
  • Alternative therapies like acupuncture, biofeedback, and relaxation techniques.



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