Indomethacin Protocols for TACs

Indomethacin: a diagnostic and therapeutic medication used in specific trigeminal autonomic cephalalgias

Indomethacin occupies a unique position in headache medicine.

A complete and sustained response to indomethacin strongly supports the diagnosis of:

• Paroxysmal hemicrania

• Hemicrania continua

This response is so characteristic that it forms part of the formal diagnostic criteria for these conditions.

Indomethacin is therefore not simply another anti-inflammatory medication — it is often used as a diagnostic trial.

Why indomethacin is different

Many medications reduce headache intensity. Indomethacin is different.

In the appropriate clinical context, it can lead to:

• Complete resolution of pain

• Disappearance of associated autonomic symptoms

• Sustained control while on therapeutic dosing

A partial response (e.g., “somewhat better”) is not typical and may suggest that the diagnosis should be reconsidered.

This clear, binary response is what makes indomethacin so valuable diagnostically.

This distinction is critical. A complete response to indomethacin can help avoid years of ineffective migraine-directed therapy when a different headache disorder is present.

An indomethacin trial is a structured medication trial of indomethacin, and has the following characteristics:

1. Start at low dose

Typically, for most patients we start at indomethacin 25 mg orally 3 times per day for 3 days.

2. Gradual increase

If tolerated and there is an incomplete response at lower dose, we usually increase to indomethacin 50 mg orally 3 times per day for 3 days.

3. Assess response

Each time the dose of indomethacin is increased, a response is evaluated. If there is complete response to indomethacin, then there is no further increase needed in the dose.

4. Maximum dose threshold

For many patients, we will increase the dose of indomethacin to a maximum of 75 mg orally 3 times per day.

5. Trial duration

A typical trial of indomethacin is 9 days long: 3 days at 25 mg orally 3 times per day, 3 days at 50 mg orally 3 times per day, and 75 mg orally 3 times per day.

6. Stop if no response

If there is no complete response after 3 days at this dose, the indomethacin trial is considered "negative" and the medication is stopped.

Gastro-protection

Indomethacin can irritate the stomach lining.

For this reason, it is usually prescribed with a proton pump inhibitor (PPI) to reduce the risk of:

• Stomach pain

• Gastritis

• Ulcers

• Gastrointestinal bleeding

This protection is an important part of a safe trial.

What to expect from indomethacin

What does “complete response” mean?

A complete response means:

• The headache stops entirely

• Flares resolve

• Pain remains absent while on adequate dose

It does not mean slight improvement, reduced intensity, or fewer attacks but ongoing pain.

The distinction is clinically important.

Safety and monitoring

Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) and can cause side effects, particularly at higher doses or with prolonged use.

Potential risks include:

• Stomach irritation or ulcer formation

• Increased blood pressure

• Kidney function changes

• Increased cardiovascular risk in certain individuals

To reduce risk, we:

• Use the lowest effective dose

• Prescribe gastric protection when indicated

• Review cardiovascular risk factors

• Monitor kidney function when appropriate

• Limit duration when possible

Next steps

If you experience a strictly one-sided headache that never switches sides, particularly one that has not responded to migraine treatments, an indomethacin trial may help clarify the diagnosis.

Discuss with your doctor whether you can benefit from a referral to the Ottawa Headache Centre for specialist assessment.

Disclaimer

This material is provided for educational purposes and does not replace independent clinical judgment or institutional protocols. Management decisions remain the responsibility of the treating clinician.