Amitriptyline for migraines and headaches

In this article:

• Does amitriptyline treat migraines?
• Mechanism of action
• Timeline
• Dosage
• Interactions and side effects
• Amitriptyline alternatives

In this article

• Does amitriptyline treat migraines?
• Mechanism of action
• Timeline
• Dosage
• Interactions and side effects
• Amitriptyline alternatives

Affecting over 37 million people in the United States, migraines are a disabling type of headache that causes intense pain. Unfortunately, migraines are often a recurrent condition, and preventive therapy is key to improving the quality of life for many. A wide range of medications are used for migraine prevention, with amitriptyline being one of them. But is amitriptyline good for migraines? As a tricyclic antidepressant (TCA), amitriptyline is a prescription drug that’s approved by the U.S. Food and Drug Administration (FDA) to treat depression. However, it’s also used off-label for migraine prevention. 

Read on to learn more about amitriptyline and migraines.  

Does amitriptyline treat migraines?

Amitriptyline is an antidepressant, but it has many additional off-label uses, including migraine prevention. While off-label use means the FDA hasn’t approved the drug for this particular use, there is substantial evidence from 12 studies that amitriptyline can be effective. However, because amitriptyline has a considerable risk of side effects, the American Headache Society and American Academy of Neurology only classify amitriptyline as “probably effective” for migraine prevention. Examples of studies supporting its use are:

• A 2010 review and meta-analysis evaluated the safety and effectiveness of TCAs, including amitriptyline, for treating migraines, tension-type headaches, and mixed headaches. Researchers found that TCAs were effective for migraine and tension-type headache prophylaxis (prevention). 
• A 2019 review found amitriptyline has the best evidence among antidepressants for use in migraine prevention. However, they note that the side effect profile of antidepressants is a concern. 

How does amitriptyline work for migraine headaches?

According to amitriptyline’s prescribing information, the drug works by increasing the levels of certain neurotransmitters, or chemicals, in the brain. These include serotonin and norepinephrine. 

Migraine headaches occur for various reasons, and researchers believe low serotonin levels may be one of the causes. Serotonin acts on nerve endings and blood vessels during a migraine attack. By doing so, it affects how the body perceives pain. More research is needed to fully understand how amitriptyline works for migraine headaches, but this may explain why amitriptyline is considered an effective antimigraine agent. 

How long does it take for amitriptyline to work for migraines?

In most cases, migraine prevention therapy takes time to work and doesn’t occur immediately. According to the American Headache Society, prevention plans are usually followed for at least eight weeks before their effectiveness is determined. Response to amitriptyline, in particular, is typically seen within four weeks. 

Amitriptyline dosage for migraines

According to American Family Physician, the recommended starting dose of amitriptyline is 10 mg once daily for migraine prevention. If this dosage isn’t preventing your migraine headaches, your healthcare provider may increase your dose gradually until you reach a dose that works for you. The recommended daily dose is typically 25 mg to 150 mg once daily. The maximum recommended dose of amitriptyline in adults is 150 mg to 300 mg per day, according to StatPearls. 

Amitriptyline is available as an oral tablet that should be swallowed whole. It comes in six strengths: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg. Because amitriptyline can cause drowsiness, it’s best to take your dose at night. It can be taken with or without food. 

Amitriptyline interactions and side effects

Like other drugs, amitriptyline has risks, including adverse effects and drug interactions. It can cause a wide variety of side effects. Fortunately, most of the common side effects are relatively mild. According to the prescribing information, these can include:

• Constipation
• Dry mouth
• Dizziness
• Drowsiness
• Headache
• Weight gain

Serious side effects may also occur. However, they are less common. These may include: 

• Confusion
• Mania
• Seizures
• Stroke
• Hallucinations
• Heart problems, including heart attack or arrhythmias
• Changes in blood sugar levels
• Eye problems

It’s important to note that, like other antidepressants, amitriptyline has a boxed warning for the risk of suicidal thoughts and behaviors in children and young adults. Taking the drug can increase the risk of suicidal thoughts and behaviors in children, adolescents, and young adults in the first few months of treatment. The risk is greater if you or your family have a risk of bipolar disorder or suicidal thoughts or actions. Due to this risk, doctors typically won’t prescribe amitriptyline for patients 24 years of age or younger unless the potential benefits outweigh the risks. Talk to a healthcare professional immediately if you or your loved ones notice any changes in mood, behaviors, thoughts, or feelings. 

Several drug interactions can occur with amitriptyline. These include prescription medicines, over-the-counter (OTC) drugs, and supplements. Interactions can alter the effects of amitriptyline or cause side effects. Some examples of drugs that may interact with amitriptyline include:

• Opioids, such as Roxicodone (oxycodone) or MS Contin (morphine)
• Monoamine oxidase inhibitors (MAOIs), including Nardil (phenelzine)
• Selective serotonin reuptake inhibitors, such as Prozac (fluoxetine)
• Triptans, including Imitrex (sumatriptan)
• Benzodiazepines, including Xanax (alprazolam)
• Sleep aids, such as Ambien (zolpidem)
• Wellbutrin (bupropion)
• Benadryl (diphenhydramine)
• Topamax (topiramate)
• St. John’s wort

Because amitriptyline can interact with quite a few drugs, it’s important to provide your healthcare provider or pharmacist with an updated medication list so they can screen for drug interactions. Additionally, amitriptyline can interact with certain foods, such as grapefruit and alcohol. 

Amitriptyline alternatives

While amitriptyline has evidence supporting its effectiveness in migraine prevention, the drug isn’t right for everyone. Luckily, a number of alternative medications are available. The following table outlines alternative medications recommended for migraine prevention.

As with any medication, it’s important to consider potential side effects and interactions and discuss them with your healthcare provider. If amitriptyline isn’t suitable, other alternatives may better fit your needs.