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It’s estimated that migraine impacts 12 percent of people in the United States. Treatment for migraine generally includes medications. These medications typically have two functions: they may either treat acute migraine symptoms or help prevent migraine attacks from occurring.

Cyproheptadine is a medication that’s sometimes used to prevent migraine attacks, particularly in children. Below, we’ll discuss cyproheptadine for migraine in more detail, its potential side effects, and how effective it is.

Cyproheptadine is a type of antihistamine. It’s used to treat allergic reactions like allergic rhinitis and hives.

In some instances, cyproheptadine may be used off-label to prevent migraine. Off-label means that a drug is being used for a purpose that differs from what the Food and Drug Administration (FDA) has approved it for.

Cyproheptadine is mainly used for migraine prevention in children and adolescents. It may also be a potential option during pregnancy, as many preventative migraine medications aren’t safe to use if you’re pregnant.

Serotonin is a type of neurotransmitter that helps to facilitate communication between nerve cells. Changes in serotonin levels can lead to migraine attacks.

Cyproheptadine is both an histamine and a serotonin antagonist. That means that it can compete with serotonin for receptor sites in the brain. In this way, it can block the activity of serotonin, helping to prevent a migraine attack.

Read more about migraine.

It’s estimated that the prevalence of migraine is about 3 percent in younger children and about 20 percent in adolescents. Cyproheptadine is often used to prevent migraine attacks in this population.

While cyproheptadine hasn’t undergone clinical trials for this purpose, it’s been reported to be effective at reducing both the frequency and intensity of migraine attacks in children and adolescents.

In addition to cyproheptadine, other preventative migraine medications that can be used for children include:

  • Propranolol. A type of blood pressure medication, propranolol is a beta-blocker, which helps control heart rhythm.
  • Topiramate. Primarily used to treat seizures, topiramate is most often prescribed in conjunction with other medications to treat partial and tonic-clonic type seizures.
  • Amitriptyline. A tricyclic antidepressant, amitriptyline is mainly prescribed to help alleviate the symptoms of depression.

Cyproheptadine is available as an oral tablet. Each tablet contains 4 milligrams (mg) of cyproheptadine.

According to the prescribing information for cyproheptadine, the recommended dosage is:

  • Age 2 to 6: 2 mg, or one half of a tablet, given 2 to 3 times per day. Do not exceed 12 mg in a day.
  • Age 7 to 14: 4 mg given 2 to 3 times per day. Do not exceed 16 mg in a day.
  • Age 15 and over: The dosage used is typically between 4 and 20 mg per day, although in some instances 32 mg per day may be needed. It’s recommended that cyproheptadine is started at 4 mg per day and adjusted from there.

The total dose of cyproheptadine for migraine prevention has been reported to range between 12 to 36 mg per day. Doses may be given either 2 to 3 times per day or at bedtime to prevent daytime sleepiness.

Since cyproheptadine is used off-label for migraine, always follow your doctor’s instructions carefully when taking it. Be sure to follow up with them if you have bothersome side effects or cyproheptadine isn’t effective at preventing migraine attacks.

According to GoodRx, the average cost of filling a prescription of cyproheptadine is $54.28.

But the cost of cyproheptadine can vary based on other factors. Some examples include the pharmacy that you fill your prescription at as well as the type of insurance that you have, if applicable.

The most common side effects of cyproheptadine are sleepiness (sedation) and weight gain. It’s also possible that excitability may occur, particularly in younger children.

Other less common side effects of cyproheptadine are:

It’s also possible to take too much cyproheptadine. Potential signs of an overdose can include:

If you suspect that someone has overdosed on cyproheptadine, seek medical attention immediately. Go to the emergency room or call 911.

Monoamine oxidase inhibitors (MAOIs), a type of antidepressant, can interact with cyproheptadine. When an MAOI is taken with cyproheptadine, the effects of cyproheptadine can be enhanced and prolonged.

Because cyproheptadine has a sedating effect, it can enhance the effects of other drugs that also have sedative properties. As such, it’s important to avoid taking cyproheptadine along with alcohol or other sedatives, including:

  • benzodiazepines like Xanax and Valium
  • barbiturates like Luminal and Nembutal
  • hypnotics like Ambien
  • opioids like OxyContin and Vicodin

Who should avoid taking cyproheptadine?

Individuals who should avoid taking cyproheptadine include:

It’s important to talk with your doctor before taking cyproheptadine if you have the following health conditions:

Now that we’ve covered many of the details of cyproheptadine for migraine, let’s discuss how effective it is.

Effectiveness in children

Although cyproheptadine is often used to prevent migraine in children and adolescents, studies on its effectiveness in this population are limited. Overall, larger, high-quality clinical trials are needed.

A 2019 review on migraine prevention in children mentions the results from a 1977 study. In this study, cyproheptadine was given for 3 to 6 months. Improvement was seen in 68 percent of participants while a remission occurred in 21 percent.

Effectiveness in adults

As in children, studies into the effectiveness of cyproheptadine for migraine prevention in adults are scarce.

An old 2000 study compared the effectiveness of cyproheptadine, propranolol, or both in 204 people between the ages of 17 and 53. While the combination was most effective at preventing migraine, 4 mg of cyproheptadine per day was found to be as effective as 80 mg of propranolol per day.

A small 2013 study observed the effects of 4 to 8 mg of cyproheptadine in 12 individuals who hadn’t responded to other preventative medications. A decrease in migraine frequency was seen, with an average attack frequency of 2.6 attacks per month, compared to over 10 attacks per month prior to cyproheptadine.

Other even older studies are mentioned in a 2019 review, which concluded that there was currently insufficient support for using antihistamines like cyproheptadine in migraine prevention in adults. These older studies were:

  • A 1964 study where improvement was seen in 46 percent of participants receiving 12 to 24 mg per day of cyproheptadine. But this result wasn’t statistically analyzed compared to the placebo.
  • A 1970 study where 40 percent of people receiving 4-8 mg of cyproheptadine 3 times a day reported improvement after 1 month.

Cyproheptadine is a type of antihistamine. It can be used off-label to prevent migraine attacks, particularly in children and adolescents.

Although clinical trial data is limited, clinical observations have found that cyproheptadine can decrease migraine frequency and intensity in children and adolescents. Other types of preventative medications are often used in adults.

Cyproheptadine is given 2 to 3 times per day or before bedtime. The most common side effects are sedation and weight gain. Let your doctor know if cyproheptadine is causing unpleasant side effects or isn’t working to prevent migraine attacks.