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If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.
What is amitriptyline, and how does it work?
Amitriptyline (brand name Elavil) is a prescription medication commonly used to treat depression. It belongs to the tricyclic antidepressant drug class. The exact mechanism of how it works is not entirely understood, but amitriptyline affects the levels of norepinephrine and/or serotonin in the central nervous system. Both norepinephrine and serotonin are specialized chemicals in the brain (neurotransmitters) that are important for communication between nerves and affect mood. Amitriptyline also blocks histamine, causing you to feel sleepy after taking it, as well as receptors called muscarinic receptors, leading to effects like dry mouth, blurred vision, and confusion (Thour, 2020). Other examples of tricyclic antidepressants include desipramine and nortriptyline.
What is amitriptyline used for?
Amitriptyline is FDA-approved to treat major depressive disorder (DailyMed, 2019):
Major depressive disorder (often simply called depression) is more than just “feeling sad” or “blue.” It is one of the most common mental health disorders in the U.S. and can affect all aspects of your life, like working, sleeping, eating, relationships, social life, etc. (NIMH, 2018). Common symptoms of depression include (NIMH, 2018):
- Angry outbursts or irritability
- Feelings of worthlessness, helplessness, or guilt
- Feeling hopeless, sad, or anxious
- Trouble concentrating
- Loss of interest or pleasure in everyday activities and hobbies
- Difficulty sleeping (insomnia) or sleeping too much
- Feeling tired all of the time
- Increased or decreased appetite and weight changes
- Unexplained physical problems, like headaches or stomach issues
- Frequent thoughts of death or suicide, or suicide attempts
Everyone has experienced a “bad day” or “feeling down,” sometimes triggered by life stressors; however, these episodes usually last for a short time. If, on the other hand, you are experiencing any of these symptoms almost every day, for two weeks or more, then you may have depression. The mainstay of treatment usually includes psychotherapy, medication, or some combination of the two (NIMH, 2018). Amitriptyline may help improve the symptoms of depression.
Sometimes healthcare providers use amitriptyline “off-label”—this means that the FDA hasn’t approved amitriptyline for that specific purpose. Examples of “off-label” uses for amitriptyline include treating chronic pain, trouble sleeping (insomnia), irritable bowel syndrome, interstitial cystitis (bladder pain syndrome), migraines, post-herpetic neuralgia (lasting pain after a shingles infection), and sialorrhea (excessive drooling) (Thour, 2020).
Many conditions, including chronic fatigue syndrome, fibromyalgia, and diabetic neuropathy, can give you long-lasting or chronic pain, and amitriptyline may improve pain symptoms. Chronic fatigue syndrome is a long-term illness that causes severe fatigue, sleep problems, muscle aches, joint pain, and headaches (CDC, 2020). Amitriptyline may improve both chronic pain and sleep problems.
Fibromyalgia causes pain all over, sleep problems, and fatigue, as well as depression, tingling or numbness, and digestive issues. You are at an increased risk for developing fibromyalgia if you are female, have post-traumatic stress disorder (PTSD), or a family history of fibromyalgia. No one knows what causes fibromyalgia, but treatment may improve symptoms. Drugs like amitriptyline may help, especially if combined with stress management strategies, exercise, improved sleep habits, and cognitive behavioral therapy (CDC, 2020).
Diabetic neuropathy occurs when diabetes damages your nerves, commonly the ones to your hands and feet (peripheral neuropathy). Up to half of all people with diabetes have peripheral diabetic neuropathy (NIDDK, 2018). Symptoms of diabetic neuropathy include pain (also referred to as neuropathic pain), tingling, numbness, burning, and weakness. Tricyclic antidepressants, like amitriptyline, can help with the pain, but it won’t change the nerve damage. Managing your diabetes is the best way to keep your diabetic neuropathy from getting worse.
Chronic pain syndrome: what is it, symptoms, treatment
Everyone has experienced sleepless nights because of one reason or another—work stress, relationship issues, trauma, etc. Usually, this goes back to normal after a few days or weeks. However, insomnia is a sleep disorder in which you have trouble falling asleep, staying asleep, or both and lasts for a month or more. It is often caused by some other problem, like caffeine or alcohol use, medical conditions, medications, or other sleep disorders. Amitriptyline can make you sleepy, so some have found it helpful in treating their insomnia.
Irritable bowel syndrome (IBS)
Irritable bowel syndrome (IBS) is caused by a problem with how your gut and brain work together. Most people experience abdominal pain, along with constipation, diarrhea, or both. We don’t know what causes IBS, but it may be related to stress, a history of abuse, depression, bacterial infections, or food intolerances (NIDDK, 2017). Amitriptyline may improve abdominal pain from IBS, along with improved sleep, exercise, and decreased stress.
Interstitial cystitis (bladder pain syndrome)
Interstitial cystitis, also known as bladder pain syndrome, causes long-term feelings of pain and pressure in your bladder. Many people also experience urinary tract symptoms like needing to urinate more frequently or urgently, stream starting and stopping during urination, straining, feeling like your bladder is still full after urinating, etc. The first phase of treatment involves lifestyle changes, like decreasing stress and limiting irritating food/drink (AUA, n.d.). Amitriptyline may help with the symptoms of interstitial cystitis by slowing down the nerves that carry pain sensations and decreasing bladder spasms (AUA, n.d.)
A “bad headache” doesn’t do a migraine headache justice. A migraine is a throbbing headache that is often made worse by sudden head movements, loud sounds, or light—this is why some people with migraines lock themselves in a dark room until the episode passes. Migraines sometimes come with other symptoms like double vision, nausea, vomiting, and dizziness. Many will experience an aura (visual signs like colored lines or sensory changes like temporary numbness or weakness of a limb) that lets them know that a migraine is coming. Amitriptyline can help decrease the frequency of migraine headaches (Modi, 2006).
Shingles (also called herpes zoster) is a reactivation infection with the varicella-zoster virus, the same virus that causes chickenpox. After having chickenpox, usually as a child, the virus goes into hiding in your nervous system. At some point, it may reactivate, affecting only the nerve where it was hiding—that is why shingles typically only shows up in a specific location, the area fed by that unfortunate nerve. The rash of a shingles outbreak often comes with a burning, painful sensation that usually lasts about 2–4 weeks.
Unfortunately, approximately 10% of people with shingles will experience continued pain for three months or longer after the rash—this is called post-herpetic neuralgia (Hadley, 2016). Tricyclic antidepressants like amitriptyline may help with the symptoms of this chronic pain, especially when combined with other treatments.
Shingles rash: how to identify, treat, and prevent it
Sialorrhea (excessive drooling)
Drooling is a condition that most people associate with babies. However, if it persists beyond the age of four, it becomes a pathologic medical condition called sialorrhea (Hockstein, 2004). Sialorrhea is excessive drooling that may accompany neurologic conditions like cerebral palsy, Parkinson’s disease, or strokes. This drooling is often due to poor facial muscle control. Sialorrhea causes physical and psychosocial consequences, like chapping of the skin around the mouth, dehydration, embarrassment, and social withdrawal. Amitriptyline may slow the production of saliva, thereby improving drooling (Hunter, 1995).
Side effects of amitriptyline
Black box warning from the U.S. Food and Drug Administration (FDA, 2014): Antidepressants, like amitriptyline, increase the risk of suicidal thoughts and behaviors, especially in children, teenagers, or young adults. Families and caregivers should be on the lookout for mood changes, suicidal thoughts, or suicidal attempts, especially during the first few months of using amitriptyline or if the dose increases. Amitriptyline is not FDA-approved for use in people under 18 years of age.
Common side effects (MedlinePlus, 2017):
- Weight gain
- Dry mouth
- Blurred vision
- Skin rash
- Change in libido
Serious side effects (DailyMed, 2019):
- Withdrawal symptoms: stopping amitriptyline suddenly may lead to withdrawal symptoms of nausea, headache, and feeling unwell
- Heart attacks
- Irregular heartbeats (arrhythmias)
- Low blood pressure (hypotension), especially after standing from sitting (orthostatic hypotension)
- Angle-closure glaucoma
- Bone marrow suppression
This list does not include all possible side effects of amitriptyline, and others may occur. Seek medical advice from your pharmacist or healthcare provider for more information.
Antidepressants that cause weight loss
Before starting amitriptyline, seek medical advice regarding any other medications to avoid any potential drug interactions. Tell your healthcare provider or pharmacist if you are taking other prescription or over-the-counter medicines, as well as herbal supplements. Possible drug interactions include (DailyMed, 2019):
- Topiramate: Topiramate treats seizures and decreases the frequency of migraine headaches. If you take it with amitriptyline, you may have an increase in your amitriptyline concentration and may need a dose adjustment to prevent side effects.
- Drugs that block the liver’s p450 system: Amitriptyline is metabolized by the liver’s p450 system. Taking this drug with medications that block the p450 system increases the levels of amitriptyline and can lead to toxicity. Examples of medicines that fall into this category include cimetidine, quinine, and selective serotonin reuptake inhibitors (SSRIs) like fluoxetine (brand name Prozac; see Important Safety Information), sertraline (brand name Zoloft; see Important Safety Information), and paroxetine (brand name Brisdelle, Paxil; see Important Safety Information).
- Monoamine oxidase inhibitors (MAOIs): You should not use amitriptyline within fourteen days of taking MAOIs antidepressants like selegiline (brand name Emsam), tranylcypromine (brand name Parnate), phenelzine (brand name Nardil), and isocarboxazid (brand name Marplan). Both MAOIs and amitriptyline affect serotonin levels, and using them together can lead to serotonin syndrome (fever, high blood pressure, confusion, and at worst case, death).
- Cisapride: Cisapride is a drug used to promote gastrointestinal tract movement. Taking cisapride with amitriptyline may interfere with the electrical signaling in the heart and increases the risk of irregular heartbeats (arrhythmias).
- Guanethidine: This medication is used to treat high blood pressure. Combining it with amitriptyline may make guanethidine less effective at lowering blood pressure.
This list does not include all possible drug interactions with amitriptyline, and others may exist. Check with your pharmacist or healthcare provider for more information.
Who should not use amitriptyline (or use with caution)?
Certain groups of people are at higher risk of side effects with amitriptyline and should either avoid using it or use it with caution and careful monitoring. Examples of these groups include (DailyMed, 2019):
- Pregnant or Nursing Women: According to the FDA, amitriptyline is Pregnancy Category C; this means that there is not enough data to say whether or not amitriptyline is safe during pregnancy. There have been a few reports of adverse effects in infants whose mothers took amitriptyline. Also, research shows that amitriptyline enters breast milk. Therefore, the decision to take amitriptyline should consider both the potential risks to the baby and the benefits to the mother.
- People with bipolar disorder: Amitriptyline may precipitate a mixed/manic episode in people with bipolar disorder. Amitriptyline is not FDA-approved to treat bipolar depression.
- People with heart problems: Amitriptyline can affect the heart’s electrical system and lead to abnormal heart rhythms and irregular heartbeats. Heart attacks and strokes can occur with amitriptyline, so people with preexisting heart conditions should talk to their healthcare provider about their medical issues before starting amitriptyline.
- People with thyroid problems or taking thyroid medications should be closely monitored while taking amitriptyline.
- People who have or are at risk for angle-closure glaucoma: Amitriptyline can cause pupillary dilation, which may trigger an episode of angle-closure glaucoma (high eye pressure, eye pain, eye redness, blurred vision, halos around lights). These episodes of angle-closure glaucoma can lead to permanent vision loss, especially if not promptly treated. Angle-closure glaucoma usually only occurs in people with “narrow angles in the eye,” meaning that the front part of the eye is anatomically different. Your healthcare provider may recommend an eye exam before starting amitriptyline.
- People with diabetes: Amitriptyline can affect glucose regulation and should be used with caution in people with diabetes.
- People with myasthenia gravis: Amitriptyline can exacerbate myasthenia gravis, a neuromuscular condition that leads to muscle weakness.
- People with seizures: Amitriptyline can decrease the seizure threshold, meaning that you are more likely to have a seizure while taking this drug. Therefore, people with seizure disorders should use amitriptyline with caution.
This list does not include all at-risk groups, and others may exist. Talk to your healthcare provider or pharmacist for more information.
Amitriptyline hydrochloride (brand name Elavil) tablets are usually taken by mouth one to four times per day. The tablets come in 10 mg, 20 mg, 50 mg, 75 mg, and 100 mg strengths.
Most insurance plans cover amitriptyline. The cost for a 30-day supply ranges from $3.60 to over $37, depending on the dose (GoodRx.com).
- American Urology Association (AUA). (n.d.). Urology Care Foundation: What is Interstitial Cystitis(IC)/Bladder Pain Syndrome?. Retrieved on September 23, 2020 from https://www.urologyhealth.org/urologic-conditions/interstitial-cystitis
- Centers for Disease Control and Prevention (CDC). (2020). Fibromyalgia. Retrieved on September 23, 2020 from https://www.cdc.gov/arthritis/basics/fibromyalgia.htm
- Centers for Disease Control and Prevention (CDC). (2020). Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Retrieved on September 23, 2020 from https://www.cdc.gov/me-cfs/index.html
- DailyMed. (2019). Amitriptyline Hydrochloride tablet, film coated. Retrieved on September 23, 2020 from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e6d2c80-fbc8-444e-bdd3-6a91fe1b95bd
- GoodRx.com. (n.d.). Amlodipine / Benazepril. Retrieved September 23, 2020 from https://www.goodrx.com/amitriptyline
- Hadley, G. R., Gayle, J. A., & Ripoll, J. (2016). Post-herpetic Neuralgia: a Review. Curr Pain Headache Rep 20, 17. doi: 10.1007/s11916-016-0548-x. Retrieved from https://link.springer.com/article/10.1007%2Fs11916-016-0548-x
- Hockstein, N. G., Samadi, D. S., Gendron, K., & Handler, S. D. (2004). Sialorrhea: a management challenge. American family physician, 69(11), 2628–2634. Retrieved from https://pubmed.ncbi.nlm.nih.gov/15202698/
- Hunter, K. D., & Wilson, W. S. (1995). The effects of antidepressant drugs on salivary flow and content of sodium and potassium ions in human parotid saliva. Archives of oral biology, 40(11), 983–989. doi: 10.1016/0003-9969(95)00079-5. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/0003996995000795?via%3Dihub
- MedlinePlus. (2017). Amitriptyline. Retrieved on September 23, 2020 from https://medlineplus.gov/druginfo/meds/a682388.html
- Modi, S., & Lowder, D. M. (2006). Medications for migraine prophylaxis. American family physician, 73(1), 72–78. Retrieved from https://pubmed.ncbi.nlm.nih.gov/16417067/
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). (2017). Irritable Bowel Syndrome. Retrieved on September 23, 2020 from https://www.niddk.nih.gov/health-information/digestive-diseases/irritable-bowel-syndrome
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). (2018). Peripheral Neuropathy. Retrieved on September 23, 2020 from https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/nerve-damage-diabetic-neuropathies/peripheral-neuropathy
- National Institute of Mental Health (NIMH). (2018). Depression. Retrieved on September 23, 2020 from https://www.nimh.nih.gov/health/topics/depression/index.shtml
- Thour, A., & Marwaha, R. (2020). Amitriptyline. [Updated Jul. 29, 2021]. In: StatPearls [Internet]. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK537225/
- UpToDate. (n.d.). Amitriptyline: Drug information. Retrieved on September 23, 2020 from https://www.uptodate.com/contents/amitriptyline-drug-information
- U. S. Food and Drug Administration (FDA). (2014). Sandoz (amitriptyline hydrochloride) Tablets. Retrieved on September 23, 2020 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/085966s095,085969s084,085968s096,085971s075,085967s076,085970s072lbl.pdf
Dr. Mike is a licensed physician and the Director, Medical Content & Education at Ro.