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Does Amitriptyline Work For Depression?

Katelyn Hagerty

Reviewed by Katelyn Hagerty, FNP

Written by Our Editorial Team

Published 04/23/2022

Updated 04/24/2022

An estimated 21 million US adults, or 8.4 percent of the entire adult population, experience one or more major depressive episodes per year, making depression one of the most common forms of mental illness.

Living with depression is difficult, so treating it is essential. If you’ve been diagnosed with major depressive disorder (MDD) or another type of depression, your healthcare provider may suggest using an antidepressant to control your symptoms.

Most people who use medication to treat depression are prescribed selective serotonin reuptake inhibitors, or SSRIs.

However, in certain cases, your healthcare provider may prescribe another antidepressant drug, such as the tricyclic antidepressant (TCA) amitriptyline. 

Amitriptyline is generally effective as a treatment for depression, especially if newer medications such as SSRIs haven’t helped to reduce the severity of your symptoms. 

However, as an older type of antidepressant, it can cause side effects and interactions that you’ll want to be aware of before starting treatment.

Below, we’ve covered everything you need to know about using amitriptyline to treat depression, from how this medication works to potential adverse effects and interactions.

We’ve also discussed some other treatment options that you may want to consider if you have a depressive disorder, including other medications and options such as psychotherapy.

What is Depression?

Depression is a common psychiatric disorder that can have a serious impact on your thoughts, feelings and behavior. It can affect almost every aspect of your daily life, from how you feel and think to your ability to perform basic functions such as sleep and socializing.

Common symptoms of depression include:

  • Feelings of sadness, anxiety or hopelessness

  • A sense of pessimism, hopelessness or guilt

  • Reduced interest in your hobbies and passions

  • Feelings of a fatigue and reduced energy levels

  • Irritability, restlessness and frustration

  • Changes in your appetite, eating habits and weight

  • Reduced concentration and difficulty remembering things

  • Difficulty falling asleep and/or staying asleep

  • Aches, pains, cramps and/or digestive problems

  • Thoughts of self-harm or suicide

To be diagnosed with depression, you’ll typically need to experience some of these symptoms on a daily or near-daily basis for a period of at least two weeks.

There are several different types of clinical depression, including some that develop in certain situations. These include perinatal depression, which develops during pregnancy, and atypical depression, which often involves unique symptoms. 

If you’re worried that you might have depression, it’s important to get help as soon as you can by talking to an expert.

You can do this by talking to your primary care provider, contacting a mental health provider in your area or using our online mental health services

What is Amitriptyline?

Amitriptyline is an antidepressant. It belongs to a class of drugs called tricyclic antidepressants, or TCAs. 

Tricyclic antidepressants like amitriptyline work by increasing levels of neurotransmitters, such as serotonin and norepinephrine, in your brain and body.  

Neurotransmitters are naturally-occurring chemicals that are responsible for regulating certain functions within your body. 

More specifically, serotonin and norepinephrine are involved in managing your moods, feelings of anxiety, happiness, alertness and arousal. Low levels of these chemicals may contribute to an increased risk of developing depression and other mental health conditions.

These days, amitriptyline and other tricyclic antidepressants generally aren’t used as first-line medicines for depression. Instead, most people with depression are prescribed newer drugs, such as SSRIs or serotonin-norepinephrine reuptake inhibitors (SNRIs).

These newer antidepressants are more selective in their effects within your body and have a lower risk of causing certain side effects.

However, TCAs like amitriptyline are still used in antidepressant therapy, especially for people who don’t experience improvements from newer medications for treating depression. 

If you have depression that doesn’t get better with an SSRI or SNRI, your healthcare provider may prescribe amitriptyline or a similar TCA to help reduce the severity of your symptoms and improve your wellbeing.

Amitriptyline is sold as an oral tablet. The recommended initial dose for treating depression is 25mg per day, which is usually taken at bedtime. This dose may be increased to a maximum of 150 to 300mg per day over the course of several weeks.

Although amitriptyline is only approved by the FDA as a medication for depression, like many other antidepressants, it’s also prescribed off-label to treat other conditions.

Common off-label uses for amitriptyline include the treatment of:

  • Anxiety

  • Post-traumatic stress disorder (PTSD)

  • Diabetic neuropathy, fibromyalgia and other forms of chronic pain

  • Sleep conditions, such as insomnia

  • Interstitial cystitis (bladder pain syndrome)

  • Irritable bowel syndrome (IBS)

  • Sialorrhea (excessive saliva)

  • Postherpetic neuralgia

  • Migraines


Our guide to tricyclic antidepressants goes into more detail about how other medications similar to amitriptyline work as treatments for depression and other conditions. 

Does Amitriptyline Work as a Treatment for Depression?

Depression is a severe mood disorder. If you have depression, it’s important to find a medication that properly reduces the severity of your symptoms and lets you focus on making real progress towards recovery. 

There’s no way to guarantee that any medication will work for every single person. However, the scientific research that’s available generally suggests that amitriptyline is an effective medication for treating depression, including in people who don’t respond to other antidepressants. 

In a systematic review published in the British Journal of Psychiatry in 2001, researchers looked at the results of more than 180 randomized controlled trials that involved the use of amitriptyline and other medications with antidepressant activity.

These medications included other TCAs and more modern medications for depression, such as SSRIs. 

Overall, the researchers found that slightly more people with major depression showed signs of improvements after using amitriptyline than after using other medications.

However, the people who took amitriptyline for the treatment of depression were also more likely to report adverse drug reactions (side effects) during treatment.

The researchers concluded that amitriptyline was more likely to produce improvements in major depressive symptoms than other medications, but was less well tolerated than other drugs.

Side Effects of Amitriptyline

So, what are these side effects? Like other prescription medications used to treat depression in adults, amitriptyline can cause a range of adverse reactions. Most of these are mild, although a few side effects of amitriptyline may be persistent or bothersome for some people.

Common side effects of amitriptyline include:

  • Nausea

  • Vomiting

  • Drowsiness

  • Confusion

  • Dry mouth

  • Headaches

  • Physical weakness

  • Unsteadiness

  • Tiredness

  • Confusion

  • Nightmares

  • Blurred vision

  • Constipation

  • Urinary retention

  • Excessive sweating

  • Changes in appetite 

  • Changes in weight

Like other antidepressants, amitriptyline can also cause sexual side effects, including a reduced level of interest in sex and changes that affect your sexual function.

Amitriptyline may also cause more serious side effects, including irregular heartbeat, chest pain, slowed speech, eye pain, severe skin rash, fainting and swelling that occurs in your face and/or tongue.

If you experience any of these side effects, it’s important to seek medical advice as soon as you can by contacting your healthcare provider or another medical professional. 

In addition to amitriptyline side effects, this medication may cause interactions when taken with other drugs, supplements or substances. 

When used with other medications that affect serotonin levels within your body, amitriptyline can cause a drug interaction called serotonin syndrome. 

To keep yourself safe while using amitriptyline, it’s important to inform your healthcare provider about any medications you currently use or have recently used -- for example, medications and supplements that you’ve taken within the past 14 days.

It’s particularly important to inform your healthcare provider if you’ve recently taken other types of antidepressants, including SSRIs, SNRIs or monoamine oxidase inhibitors (MAOIs).

It’s also important to inform your healthcare provider about any medical conditions you currently have, such as heart disease or issues with your heart rate, or if you’ve previously suffered from a heart attack, stroke or other cardiovascular event.

Although amitriptyline isn’t an addictive drug, it and other antidepressants can cause withdrawal symptoms if treatment is stopped abruptly. 

Symptoms of amitriptyline withdrawal include nausea, headaches and a lack of energy. If you’d like to stop taking amitriptyline, let your healthcare provider know before making any changes to the way you use this medication. 

Your healthcare provider can help you to gradually taper your dosage of amitriptyline and avoid any bad side effects that can occur as a result of antidepressant withdrawal. 

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Other Options for Treating Depression

Amitriptyline is generally an effective medication for treating depression, especially if you have depression that hasn’t responded to other treatments.

If you’re previously tried SSRIs or SNRIs and didn’t experience improvements, your healthcare provider may suggest taking a daily dose of amitriptyline to control your symptoms.

However, amitriptyline isn’t the only option that’s available for managing depression, nor is it the best form of treatment for everyone.

Other options for treating depression include newer medications such as SSRIs and SNRIs, as well as non-pharmacological forms of treatment such as psychotherapy and basic changes that you can make to your habits and lifestyle. 

Other Medications for Depression

If you develop side effects from amitriptyline, you might benefit from switching to a different type of medication for depression. 

Other antidepressants include modern medications such as SSRIs and SNRIs, which work in a more selective way within your body and are less likely to produce certain side effects, such as drowsiness. 

We offer several SSRis online, including fluoxetine (the active ingredient in Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®) and escitalopram (Lexapro®).

We also offer several serotonin-norepinephrine reuptake inhibitors (SNRIs), including duloxetine (Cymbalta®) and venlafaxine (Effexor®).

If you have sexual side effects from amitriptyline, you may benefit from switching to an atypical antidepressant and buying bupropion online (Wellbutrin®), which is linked to improved sexual health in people who use medication to treat depression.

Interested in talking with a mental health professional about your medication? You can connect with a licensed provider via our online psychiatry service and, if appropriate, access medication for depression or anxiety from your home. 

Psychotherapy (Talk Therapy)

Depression often gets better with psychotherapy, or talk therapy. This type of therapy involves working with a mental health specialist to identify and change the thoughts and behaviors that can contribute to depression.

There are many different approaches to psychotherapy, including cognitive behavioral therapy (CBT). 

You may need to take part in therapy on its own, or in combination with the use of medications such as amitriptyline or other antidepressants. 

We offer individual therapy online, allowing you to talk to a licensed therapy provider and make progress towards overcoming depression from your home.

Habits and Lifestyle Changes

There are many habits and lifestyle changes that you can make to reduce the severity of some depression symptoms and improve your quality of life. 

These include keeping yourself physically active by exercising regularly, eating a balanced diet that’s rich in vitamins, minerals and other nutrients, maintaining a consistent bedtime and daily routine, spending time with other people and avoiding alcohol, nicotine and illicit drugs.

Simple things, such as delaying important decisions until you’re more in control of your feelings, can also help you to avoid setbacks and make better mental health progress.

Our list of ways to help depression goes into more detail about healthy habits that you can use to manage your depressive symptoms and focus on recovering. 

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The Bottom Line on Taking Amitriptyline for Depression

If you’re depressed, you aren’t alone. Depression in adults is common, with tens of millions of people affected every year in the United States alone.

Amitriptyline is one of many medications for treating depression. Your healthcare provider may recommend it if you’ve tried an SSRI or SNRI without any results, or if you have a severe form of depression that they think could improve with this medication. 

If you’re prescribed amitriptyline, make sure to closely follow your healthcare provider’s advice and use it only as recommended. If you experience any negative effects, make sure to tell your healthcare provider as soon as you can. 

Interested in learning more about treating depression? You can connect with a licensed mental health provider online using our range of mental health services, or find out more about how to manage depression and anxiety using our free online mental health resources

9 Sources

Hims & Hers has strict sourcing guidelines to ensure our content is accurate and current. We rely on peer-reviewed studies, academic research institutions, and medical associations. We strive to use primary sources and refrain from using tertiary references.

  1. Major Depression. (2022, January). Retrieved from https://www.nimh.nih.gov/health/statistics/major-depression
  2. Depression. (2022, July). Retrieved from https://www.nimh.nih.gov/health/topics/depression
  3. Thour, A. & Marwaha, R. (2022, May 15). Amitriptyline. StatPearls. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK537225/
  4. Brain Hormones. (2022, January 24). Retrieved from https://www.endocrine.org/patient-engagement/endocrine-library/hormones-and-endocrine-function/brain-hormones
  5. Moraczewski, J. & Aedma, K.K. (2022, May 2). Tricyclic Antidepressants. StatPearls. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK557791/
  6. Chu, A. & Wadhwa, R. (2022, May 8). Selective Serotonin Reuptake Inhibitors. StatPearls. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK554406/
  7. Barbui, C. & Hotopf, M. (2001, February). Amitriptyline v. the rest: still the leading antidepressant after 40 years of randomised controlled trials. The British Journal of Psychiatry. 178 (2), 129-144. Retrieved from https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/amitriptyline-v-the-rest-still-the-leading-antidepressant-after-40-years-of-randomised-controlled-trials/149B8AB17D99C548445A9E40986FADF3
  8. Amitriptyline. (2017, July 15). Retrieved from https://medlineplus.gov/druginfo/meds/a682388.html
  9. Gitlin, M.J., et al. (2002). Bupropion-sustained release as a treatment for SSRI-induced sexual side effects. Journal of Sex & Marital Therapy. 28 (2), 131-138. Retrieved from https://pubmed.ncbi.nlm.nih.gov/11894796/

This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment. Learn more about our editorial standards here.

Katelyn Hagerty, FNP
Katelyn Hagerty, FNP

Kate Hagerty is a board-certified Family Nurse Practitioner with over a decade of healthcare experience. She has worked in critical care, community health, and as a retail health provider.

She received her undergraduate degree in nursing from the University of Delaware and her master's degree from Thomas Jefferson University. You can find Katelyn on Doximity for more information.

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