What is the recommended dosage of Amitriptyline (a tricyclic antidepressant) for headache treatment?

From the Guidelines

Amitriptyline should be initiated at a low dose of 10-25 mg once daily at bedtime for headache prevention, with gradual increases as needed and tolerated, to minimize side effects and optimize efficacy. The dosage may be increased to 25-100 mg per day if needed and tolerated, as this medication works by increasing levels of serotonin and norepinephrine in the brain, which helps regulate pain pathways 1. It's essential to note that amitriptyline is not used for acute headache relief but rather as a preventive treatment that may take 4-6 weeks to show full effectiveness. Side effects can include drowsiness, dry mouth, constipation, and weight gain, which is why it's typically taken at night. Patients should start at the lowest effective dose to minimize side effects, and this medication requires a prescription and should only be taken under medical supervision, as dosage needs to be individualized based on response and tolerability.

Some key points to consider when prescribing amitriptyline for headache prevention include:

• Starting with a low dose and gradually increasing as needed and tolerated
• Monitoring for side effects, such as drowsiness, dry mouth, constipation, and weight gain
• Individualizing dosage based on response and tolerability
• Avoiding use in patients with certain heart conditions, glaucoma, or those taking MAO inhibitors
• Considering the use of a headache diary to determine treatment efficacy and identify analgesic overuse 1.

It's also important to note that the use of amitriptyline for headache prevention is supported by guidelines, which recommend initiating pharmacologic treatment at a low dose and gradually increasing the dose until desired outcomes are achieved 1. Additionally, the guidelines suggest considering the use of alternative treatments, such as ACE inhibitors, ARBs, or SSRIs, if amitriptyline is not tolerated or effective 1. However, the most recent and highest quality study on this topic is from 2021, which recommends starting with a low dose of 10 mg amitriptyline once a day and titrating slowly to a maximum of 30–50 mg once a day for irritable bowel syndrome, but this can be extrapolated to headache prevention 1.

From the FDA Drug Label

For outpatients, 75 mg of amitriptyline HCl a day in divided doses is usually satisfactory. If necessary, this may be increased to a total of 150 mg per day Adolescent and Elderly Patients In general, lower dosages are recommended for these patients Ten mg 3 times a day with 20 mg at bedtime may be satisfactory in adolescent and elderly patients who do not tolerate higher dosages. The usual maintenance dosage of amitriptyline HCl is 50 to 100 mg per day. In some patients, 40 mg per day is sufficient.

The recommended dosage of amitriptyline for headache is not explicitly stated in the label, but the usual dosage range for outpatients is 75-150 mg per day. For adolescent and elderly patients, a lower dosage of 10 mg 3 times a day with 20 mg at bedtime may be satisfactory. The maintenance dosage is typically 50-100 mg per day 2.

From the Research

Amitriptyline Dosage for Headache

• The initial dose of amitriptyline for headache treatment can be as low as 10 mg daily, with most patients started on this dose 3.
• Maximum dosing can range from 2.5 to 100 mg daily, with most patients taking 10-25 mg daily 3.
• Low doses of amitriptyline (≤25 mg daily) may be effective and well-tolerated for chronic headache disorders 3.
• A study found that amitriptyline was superior to placebo in reducing headache frequency at 8 weeks, but not at subsequent time points, with a dose of 25 mg daily 4.
• Another study found that amitriptyline was effective in reducing headache frequency and severity in patients with chronic daily headache, with a dose range of 10-50 mg daily 5.

Efficacy and Safety

• Amitriptyline has been shown to be effective in reducing headache frequency and severity in patients with migraine and chronic daily headache 3, 4.
• The most commonly reported adverse effect of amitriptyline is daytime fatigue, occurring in approximately 11% of patients 3.
• Amitriptyline may be more effective than placebo in reducing headache frequency in patients with chronic tension-type headache, but the evidence is limited and inconclusive 6.

Comparison to Other Treatments

• Amitriptyline may be more effective than selective serotonin reuptake inhibitors (SSRIs) in reducing headache frequency and severity in patients with chronic tension-type headache 6.
• Amitriptyline may be less effective than botulinum toxin type A in reducing headache frequency and severity, but the evidence is limited and inconclusive 7.