Is low-dose amitriptyline (Amitriptyline) effective in preventing migraine episodes?

From the Guidelines

Low-dose amitriptyline is effective in preventing migraine episodes, as supported by the most recent guidelines from the American College of Physicians 1. The typical preventive dose ranges from 10-50 mg daily, usually taken at bedtime to minimize daytime sedation. Treatment should begin at a low dose (often 10 mg) and gradually increase if needed and tolerated, as recommended by the clinical guideline from the American College of Physicians 1. Patients should take amitriptyline consistently for at least 2-3 months before determining its effectiveness, as preventive benefits may take time to develop. Some key points to consider when prescribing amitriptyline for migraine prevention include:

• Initiating treatment at a low dose and gradually increasing as needed and tolerated
• Considering the use of a headache diary to determine treatment efficacy and identify analgesic overuse
• Reevaluating the balance of benefits, harms, and costs of preventive treatment with the patient after a reasonable trial period
• Discussing potential adverse events, particularly in people of childbearing potential and those who are pregnant or breastfeeding Amitriptyline works by increasing levels of serotonin and norepinephrine in the brain, which helps regulate pain pathways and stabilize the trigeminal system involved in migraine generation, as noted in the guideline from the American College of Physicians 1. It also has effects on sleep quality, which can be beneficial since poor sleep is a common migraine trigger. Patients with heart conditions, glaucoma, urinary retention issues, or those taking certain medications like MAO inhibitors should use caution or avoid amitriptyline, as recommended by the guideline 1. The medication should be continued for 6-12 months if effective before considering a gradual taper to determine if ongoing treatment is necessary, based on the clinical guideline from the American College of Physicians 1.

From the FDA Drug Label

1. Dosage and Administration Oral Dosage Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance. The usual maintenance dosage of amitriptyline HCl is 50 to 100 mg per day. In some patients, 40 mg per day is sufficient.

The FDA drug label does not answer the question.

From the Research

Effectiveness of Low-Dose Amitriptyline in Preventing Migraine Episodes

• The study 2 found that low doses of amitriptyline were effective and well-tolerated in treating chronic headache disorders, with approximately 3/4 of patients experiencing improvement.
• The same study 2 also suggested that using low doses of amitriptyline may improve medication persistence, which is an important consideration in managing chronic conditions like migraines.
• Another study 3 recommended amitriptyline as a first-line agent for migraine prevention, along with other medications like propranolol and topiramate.
• A more recent study 4 considered amitriptyline as a second-line medication for migraine prophylaxis due to a greater number of adverse events, but still acknowledged its effectiveness.
• Other studies 5, 6 also listed amitriptyline as a viable option for migraine prophylaxis, although they may have ranked it differently in terms of efficacy and evidence compared to other treatments.

Comparison with Other Treatments

• A study 6 compared botulinum toxin A with other interventions, including amitriptyline, and found that botulinum toxin A was associated with a small to modest benefit for chronic daily headaches and chronic migraines.
• The same study 6 found that botulinum toxin A was not significantly different from amitriptyline in reducing migraine headaches per month.
• Another study 5 listed amitriptyline as one of the first-choice drugs for migraine prophylaxis, along with beta-blockers and topiramate.

Dosage and Tolerability

• The study 2 found that the most commonly reported adverse effect of amitriptyline was daytime fatigue, affecting approximately 11% of patients.
• The same study 2 also found that most patients were started on a dose of 10 mg daily, and the maximum dosing ranged from 2.5 to 100 mg daily, with most patients taking 10-25 mg.
• The study 2 suggested that using low doses of amitriptyline may improve tolerability and reduce the risk of adverse events.