Amitriptyline: off-label uses for certain types of pain

Amitriptyline often sold as a generic or under the brand name Elavil, is a tricyclic antidepressant drug (TCA) originally developed in the 1960s. It works by increasing the amount of substances in the brain called norepinephrine and serotonin.

While amitriptyline is approved by the FDA for the treatment of depression, it has many off-label uses as well and can be used to treat certain types of chronic pain, including conditions like fibromyalgia, nerve pain, migraines and other headaches, and bladder pain. It can also be prescribed for irritable bowel syndrome and chronic fatigue syndrome (Thour, 2020).

We’ll cover everything you need to know about amitriptyline, what it’s used for, how it works, and what potential side effects you might experience when taking it. 

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Initially developed as a treatment for depression, research has demonstrated that the drug is far more versatile, landing it “off-label” use as a pain medication. Off-label means that a drug hasn’t gone through the stringent and lengthy process required for FDA (Food and Drug Administration) approval for that use. 

Healthcare providers may, at their discretion, prescribe medications for conditions other than those the FDA has explicitly approved them for. Anything outside of the original FDA approval is considered off-label. Typically, the FDA approves a new drug for a specific use in a specific group, basically offering their seal of approval that the drug is safe and effective. 

Using a drug off label isn’t fringe, though. Off-label uses are often based on years of research and/or experience in the field. A 2001 report by the National Disease and Therapeutic Index indicated that up to 21% of prescriptions are off-label (Radley, 2006). 

Amitriptyline is one of the 100 most commonly prescribed medications in the United States, prescribed to nearly 2 million people in the US in 2018 alone (AHRQ, 2020). Low doses of some types of antidepressants–particularly tricyclic ones like amitryptiline–have been shown to alleviate pain associated with certain conditions in some patients. While the antidepressant effects of TCAs can take two to four weeks, the pain-relieving effects tend to appear even faster–sometimes within one week of starting treatment, and at a much lower dose than is typically used to treat depression (Lynch, 2001).

Amitriptyline is an option for pain management in certain situations, but it won’t work for everything or everyone. We’ve got a list of some of the conditions that can improve with amitriptyline. 

Fibromyalgia

Fibromyalgia (FM) is a condition characterized by chronic pain all over the body, tender spots, and tingling or numbness in the arms and legs. While we aren’t sure exactly what causes it, and we have yet to find a cure, science has shown that a multi-disciplinary approach combining medications and behavioral changes (like exercise and cognitive behavioral therapy (CBT) can make people living with fibromyalgia feel a whole lot better (CDC, 2020).

Until recently, amitriptyline was the most commonly prescribed medication for FM patients, though in the early to mid-2000s, new drugs came on the market. Pregabalin (Lyrica), duloxetine (Cymbalta), and milnacipran (Savella) all received FDA approval for treatment of FM. However, amitriptyline remains one of the common first-line treatments for FM. An analysis of multiple studies showed about 24% of FM patients found significant pain relief with amitriptyline (Moore, 2015-a).

Chronic fatigue syndrome (CFS)

Chronic fatigue syndrome (CFS) is a condition characterized by muscle and joint pain and tiredness, and it’s what’s called a “diagnosis of exclusion,” which means that it can only be diagnosed when all other conditions have been ruled out (Bhatti, 2019). Tricyclic antidepressants have been shown to be effective in some patients at reducing pain and promoting better sleep (Castro-Marrero, 2017).

Neuropathic pain

Neuropathic pain, unlike pain from a cut or a bruise in which nerves receive signals from the tissues, neuropathic pain is pain caused by damage to the nerves themselves. Nerve damage is often described as burning or shooting pain, “pins and needles,” numbness or itching. It can be caused by a range of underlying conditions, but some of the more common causes include:

• Diabetic neuropathy, typically in the hands and feet (peripheral neuropathy), is found in over 20% of type 1 diabetes patients and 50% of type 2 patients (Pop-Busui, 2016).

• Postherpetic neuralgia: If you had chickenpox as a child, you might be at risk of developing a condition called shingles. This condition typically becomes more common the older you get, but it can occur at any age in a person who had chickenpox. This type of nerve pain is the most common complication of shingles (Johnson, 2004).

• Post-stroke pain, affecting just over 10% of stroke patients (Treister, 2016).

Irritable bowel syndrome (IBS)

Irritable bowel syndrome (IBS) is a condition characterized by frequent abdominal pain and diarrhea or constipation, affecting an estimated 11.2% of people globally (Card, 2014). Amitriptyline has been shown to be an effective treatment for alleviating symptoms of IBS in adults and adolescents (Chao, 2013; Bahar, 2008).

Interstitial cystitis

Interstitial cystitis (also called “bladder pain syndrome”) is ongoing pain in the lower abdomen and/or bladder, often accompanied by a constant feeling like you need to pee and frequent urination. It’s far more common in women than in men, and the cause of it remains unknown (NIDDK, 2017). It is usually initially treated with lifestyle and diet changes, as well as physical therapy. Multiple studies have shown amitriptyline to be a relatively safe and effective treatment for many patients (Hanno, 1989; Ophoven, 2005).

Chronic tension and migraine headaches

Chronic tension and migraine headaches are an unfortunate part of life for many people, with the latter being particularly debilitating, as anyone who has suffered them can tell you. Amitriptyline is considered one of the most effective first-line options (Silberstein, 2009).

Amitriptyline is generally well-tolerated in low doses. In one study, though, up to 18% of patients chose to stop therapy due to side effects (Bryson, 1996). The most common side effects of amitriptyline can include (MedlinePlus, 2017):

• Drowsiness/sleepiness

• Nausea or vomiting

• Headaches

• Dry mouth

• Weight gain/appetite changes

• Difficulty peeing

• Constipation

• Blurred vision

• Confusion

• Dizziness

• Changes in libido

• Nightmares

While it may be tempting to stop taking this medication, it’s important to consult with your healthcare provider first since some people can experience withdrawal symptoms, including nausea, fatigue, and headaches, when stopping the medication suddenly, and your healthcare provider may prefer to lower your dosage gradually.

Amitriptyline has also been reported to cause serious side effects, including (MedlinePlus, 2017):

• Heart attack

• Stroke

• Irregular heartbeats

• Chest pain

• Numbness in the arms or legs

• Slurred or difficult speech

• Skin rash or hives

• Swelling of the face and/or tongue

• Yellowing of the skin and/or eyes

• Lowered blood pressure/orthostatic hypotension (sudden drop in blood pressure when you stand up)

• Upper body muscle spasms in the jaw, neck, and back.

• Fainting

• Seizures

• Hallucinations

If you notice any of the above adverse effects, contact your healthcare provider immediately. Talk to your doctor before abruptly discontinuing treatment.

Tell your healthcare provider about any medications you are already taking before starting treatment with amitriptyline. Certain medications, when combined with amitriptyline, can cause potentially dangerous drug interactions. These include, but are not limited to (MedlinePlus, 2017):

• Monoamine oxidase inhibitors (MAOIs). You should not take amitriptyline if you are taking or have recently taken MAOIs. It is recommended that at least 14 days elapse between the end of MAOI therapy and starting amitriptyline.

• Cisapride (Propulsid) for nighttime heartburn

• Guanethidine (Ismelin) for high blood pressure

• Quinidine (Quinidex) used to treat irregular heartbeats or malaria

• Selective serotonin reuptake inhibitors (SSRIs) or any antidepressants

• Sedatives, sleeping pills, or tranquilizers.

• Thyroid medications

Your doctor will want to know if any of the following conditions apply to you, as you may be at a higher risk for some side effects (MedlinePlus, 2017):

• If you are pregnant, plan to become pregnant, or are nursing

• If you have a heart problem or have suffered a heart attack recently 

• If you have any liver or kidney disease

• If you are a heavy drinker of alcohol

• If you are diabetic

• If you have had glaucoma

• If you have ever had a seizure

This is not an exhaustive list, of course, and your healthcare provider will ultimately determine if amitriptyline is right for you. 

Amitriptyline is available in doses from 10-150 mg and is sometimes taken in smaller doses throughout the day and/or a higher dose at bedtime due to its potential sedative effects. Your dosage will depend on your particular condition, age, and weight and will be determined by your doctor. 

Often patients will begin at a low dose, which is slowly increased to test tolerance. In case of a missed dose, take it when you realize it unless it is close to the time for your next dose. Never take a double dose of amitriptyline as an overdose can occur. Symptoms of overdose can include seizure, hallucinations, and coma, among others (MedLinePlus, 2017).

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Current version

November 03, 2020

Written by

Seth Gordon

Fact checked by

Yael Cooperman, MD

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About the medical reviewer

Yael Cooperman, MD, Ro

Yael Cooperman is a physician and works as a Senior Manager, Medical Content & Education at Ro.