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Can I take Amitriptyline and Modafinil together?

Drug interaction guide

Taking amitriptyline and modafinil together can increase the levels of amitriptyline in your body. This may lead to an increased risk of side effects such as extreme sleepiness, dry mouth, blurred vision, constipation, or a fast heartbeat. In some cases, it can also increase the risk of heart rhythm problems or seizures.

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Why this happens

Modafinil can slow down the liver enzymes (specifically CYP2C19) that are responsible for breaking down amitriptyline. Because the body cannot clear the amitriptyline as quickly as usual, the drug builds up in your system. Additionally, both drugs can affect heart rate and brain activity, which may lead to additive effects.

You should consult your doctor before taking these two medicines together. Your doctor may need to adjust your dose of amitriptyline or monitor you more closely for side effects. Seek medical help immediately if you experience a very fast or irregular heartbeat, severe dizziness, or fainting.

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Suicidal thoughts and mood changes

Amitriptyline can increase the risk of suicidal thoughts or self-harm, particularly when first starting treatment or changing doses. Seek immediate medical help if your mood changes or you feel depressed.

Heart conditions

Do not take amitriptyline if you have recently had a heart attack or have heart rhythm problems (arrhythmias), as it can affect the electrical signals in your heart.

Hormonal contraception (Pill, patch, or implants)

Modafinil makes hormonal contraceptives less effective. You must use an additional barrier method (like condoms) during treatment and for 2 months after stopping.

Severe skin rash

Stop taking modafinil and seek urgent medical help if you develop a rash, skin peeling, or mouth sores, as it can cause rare but life-threatening skin reactions.

Alcohol

You should avoid or strictly limit alcohol while taking amitriptyline. Both substances cause drowsiness and slow your reactions; combining them can lead to dangerous levels of sedation, impaired coordination, and increased risk of falls. Alcohol can also worsen the side effects of the medication.

Caffeine (Coffee, tea, energy drinks)

Limit your intake of caffeine while taking modafinil. Because both are stimulants, combining them can increase the risk of side effects such as a racing heart (palpitations), anxiety, jitters, high blood pressure, and difficulty sleeping.

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Taking multiple medicines? Our Medicines Interaction Checker helps you check whether your prescriptions, over-the-counter medicines, and supplements are safe to take together. Simply search for your medicines to see potential interactions and what to do about them.

Disclaimer

This information is for general educational purposes only and should not be relied upon as a substitute for professional medical advice. Always consult your GP, pharmacist, or another qualified healthcare professional before making decisions about your medications. Individual circumstances may vary, and only a healthcare professional who knows your medical history can provide personalised guidance.

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Article history

The information on this page is written and peer reviewed by qualified clinicians.

  • 25 Jan 2026 | Originally published
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