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Amitriptyline For Pain

This article provides everything you need to know about amitriptyline for pain alongside the best natural alternative to address your pain. Pain is an obnoxious stimulus that nobody wants to experience but the truth is that pain is a protective mechanism of the body that makes you aware of undergoing injuries and damage.

To end your agony you would have used a non-steroidal anti-inflammatory drug at least once in your life. For the management of pain, there is a myriad of pain-killer medicines available on the market. Due to the complex makeup of the human body, there are different classes of pain-killer drugs designed for different types of pain stimuli.

An antidepressant drug i.e. amitriptyline is used to manage chronic pain. In the following paragraphs, we shall be discussing how amitriptyline works to reduce pain.

What Is Amitriptyline For Pain?

Amitriptyline sold as Amitriptyline HCL is an antidepressant drug prescribed for different mood and mental health disorders including:

  • Anxiety disorders
  • Major depressive disorders
  • Mood disorders
  • Sleep disorders

It belongs to a class of medicinal drugs known as tricyclic antidepressants. Amitriptyline is an FDA-approved drug for treating depression.

Mechanism Of Action

Research has revealed that the antidepressant drug brings about therapeutic effects by increasing neurotransmission of noradrenergic or serotonergic transmitters. It achieves this by blocking the norepinephrine/serotonin transporters (NET/SERT) at the presynaptic terminals.

Uses Of Amitriptyline For Pain

This very drug is FDA-approved only for depression, however, amitriptyline is used for the following conditions as well:

  • Anxiety
  • Insomnia
  • Irritable bowel syndrome
  • Interstitial cystitis
  • Chronic pain
  • Migraine prophylaxis
  • Post-traumatic stress disorder (PTSD)
  • Postherpetic neuralgia
  • Sialorrhea (excessive salivation)

Amitriptyline For Pain Reduction

The drug amitriptyline has shown promising results in the management of different types of chronic pain issues including:


The bone degenerative disease can be age-related or auto-immune in nature. Osteoarthritis is a condition where the bones disintegrate with the passage of time and cause severe joint aches.

On the other hand, rheumatoid arthritis is a chronic joint disorder that causes pain due to the accumulation of auto-antibodies.

Whatever, the type, the ultimate result is persistent pain that usually doesn’t respond to over-the-counter pain killers.

Animal studies in the 1980s found the anti-inflammatory role of tricyclic antidepressants (amitriptyline) and highlighted the need for further studies to investigate their analgesic role in arthritis.

Therefore, 32 patients with rheumatoid arthritis were treated with amitriptyline in the late 1980s. The randomized controlled trial concluded that amitriptyline is associated with a significant reduction in pain and tenderness in joints.

Modern studies have now revealed that amitriptyline also improves mood while reducing pain. Being exposed to never-ending pain makes you hyperalgesic and likely to suffer from mood disorders. As per a 2014 study, amitriptyline reverses hyperalgesia and enhances mood in monoarthritis patients.

Another study carried out in 2017 has found amitriptyline to be effective in treating musculoskeletal (muscle and bones) disorders.

The latest randomized controlled trial (2021) has gathered some evidence that amitriptyline improves pain symptoms and reduces disability in knee osteoarthritis patients.

Back Pain

An estimated 577 million people across the globe suffer from low back pain. The painful condition has a prevalence of 7.5% and is a leading cause of disability and days missed from work.

In cases where back pain is the result of sciatic nerve inflammation (sciatica), the effects of general analgesics are poor. In the recent past, we have seen the introduction of antidepressants as analgesic drugs. Serotonin noradrenaline reuptake inhibitors have shown to bring about some positive changes in back pain symptoms.

Amitriptyline is increasingly being used to alleviate chronic low back pain and rightly so!

Older studies didn’t find any appreciable role of low-dose amitriptyline in back pain reduction as compared to placebo. But with an increasing amount of research, the effect was more clear.

As per a 2018 randomized controlled trial, amitriptyline consumption for 3 months greatly reduced disability in back pain patients.

It was further revealed in a study that amitriptyline therapy when paired with corticosteroid injection showed superior results in treating chronic low back pain associated with radiculopathy. However, lower doses of the drug did not have any significant effects on back pain reduction.

The latest trials (2021) advocate the use of amitriptyline in providing pain relief to patients gnawing with back pain. The drug seemed to be generally safe and significantly reduced pain and disability.


The unique pain disorder i.e. fibromyalgia has baffled healthcare professionals for years. The disorder has no significant underlying cause for the pain and is believed to be the result of neurotransmission abruptions.

Antidepressant therapy has been under the microscope for a long time. As per a systematic review published in the British Society for Rheumatology, amitriptyline can be helpful in decreasing fibromyalgia symptoms when given for 6-8 weeks.

An old study found amitriptyline and cyclobenzaprine to be efficacious in reducing fibromyalgia pain but only for the short term. However, modern researchers believe it is effective as a first-line drug for fibromyalgia.

A detailed study revealed that tricyclic antidepressants like amitriptyline have a higher potential to target fibromyalgia pain than other analgesics.

When putting parallel to duloxetine, the drug doesn’t fail to impress as both the drugs have been found to have similar effects.

In a 2022 meta-analysis investigating the comparative efficacy of drugs for fibromyalgia, amitriptyline and duloxetine stood out while pregabalin showed no significant impact as compared to the placebo.

Therefore, tricyclic antidepressants like amitriptyline are being considered for managing chronic fibromyalgia pain in adults.

Neuropathic Pain (Nerve Pain)

One of the most stubborn pains to manage is nerve pain or neuropathic pain. The irony is that nerve pain is mostly of high severity and does not respond to over-the-counter pain killers like ibuprofen or naproxen.

Thus, an antidepressant drug can be the only choice in the management of neuropathy. There is some evidence that supports the use of topical amitriptyline for neuropathic pain.

The wonderful analgesic effect of the drug was seen in a literature review of two cases with neuropathic pain. The first patient experienced complete relief from pain in the hands and feet (due to diabetes mellitus neuropathy) with topical application of 10% amitriptyline. The other patient also reported alleviation of symptoms of chronic idiopathic axonal polyneuropathy after topical application. However, in the latter, the development of adverse effects (drowsiness) led to the halting of the therapy.

Even sciatic nerve pain can be lessened by using a combination of pregabalin and amitriptyline.

The analgesic effect is attributed to the immune-modulating effect of the drug. Amitriptyline modulates the levels of proteomes and secretomes (proteins) in the CSF (fluid in the spinal cord and the brain).

Paracetamol and amitriptyline enhance each other (synergistic effect) when given together to nerve pain patients. According to a 2021 study, the amitriptyline/paracetamol combination helps provide a superior pain-countering effect (antiallodynic effect).


Postherpetic Neuralgia (PHN)

It is a nerve pain disorder that seriously compromises the quality of life. Combination therapy of amitriptyline and fluphenazine can be efficacious in managing pain caused by postherpetic neuralgia.

As per a randomized trial, both amitriptyline and nortriptyline bring about evident pain relief in PHN patients. So, amitriptyline can be used in patients developing painful conditions after a herpes zoster infection.


The potent tricyclic antidepressant can tone down headaches and migraine pain. Amitriptyline achieves this effect by amping up the effects of serotonin (a neurotransmitter) in the brain that is associated with pain regulation and generalized well-being.

Adding amitriptyline as a treatment regimen for chronic migraine patients can be a fruitful step. As per a randomized study, amitriptyline is robust in cutting down on migraine. It is also observed that adding exercise to the daily routine enhances the impact of the drug.

Another double-blind study concluded that amitriptyline and fluoxetine are effective medicinal drugs for managing daily headaches/transformed migraines. The pain-killer effect of these drugs, however, came at the expense of adverse effects (dry mouth).

26-week therapy of amitriptyline and topiramate showed similar results in reducing migraine frequency. Despite amitriptyline being the first choice, topiramate showed better improvement in quality of life, enhanced weight loss, and improved weight satisfaction.

Alternatives to Amitriptaline


In recent years, Prolotherapy has built its reputation within the medical community for its clinically proven ability to help relieve pain.

Published research has proven its pain-relieving, anti-inflammatory and regenerative benefits.

Prolotherapy involves injecting a natural regenerative solution with tiny needles. This has been shown to stimulate the production of collagen cells, the small cells needed to help repair parts of the body and relieve pain.

As prolotherapy is helping to treat the root cause of pain, it is deemed to be a permanent fix, preventing the symptoms from returning.

How Does Amitriptyline Work To Reduce Pain?

According to the NHS, amitriptyline reduces pain by modulating the pain signals inside your brain and the spinal cord.

The analgesic effect is achieved by pumping up the levels of serotonin in your brain. Serotonin is a neurotransmitter associated with pain and mood regulation.

Serotonin receptors play a part in the regulation of nerve pain as well. Therefore, serotonin regulation carries immense importance in neuropathic pain.

Amitriptyline Vs Commonly Used Pain-Killers

Here is a look into how the antidepressant drug stands against commonly used pain killers in bringing about pain relief.

Amitriptyline Vs NSAIDs

Naproxen and amitriptyline have similar pain-relieving effects on fibromyalgia, a study suggests.

Amitriptyline Vs Tramadol

Both amitriptyline and tramadol showed excellent results in limiting postamputation pain. the antinociceptive effect of both these drugs was similar and appreciable.

Amitriptyline Vs Pregabalin

Researchers are in a constant quest to find out the better choice in treating neuropathic pain. One randomized controlled trial found pregabalin to be the better choice for diabetic neuropathy due to reduced adverse effects associated.

However, another study found both drugs to be equally efficacious in diabetic peripheral neuropathic pain.

Dosage Of Amitriptyline

Determining the right dose of amitriptyline for analgesic effect is a difficult task because it is not FDA approved for the purpose.

Amitriptyline comes in 3 different dosage strengths i.e. 10mg, 25mg and 50mg. According to the NHS, the maximum daily dose of amitriptyline for adults is 75mg. Higher doses may be recommended when curing migraine.

Side Effects Of Amitriptyline For Pain

Common side effects of amitriptyline use include:

  • Dry mouth
  • Constipation
  • Sleepiness
  • Headache
  • Sedative effects (dizziness)
  • Difficulty peeing

Serious side effects happen rarely but should be immediately reported. Serious complications of amitriptyline include:

  • Eye issues (blurred vision, glaucoma
  • Pacy and irregular heartbeat
  • Heart problems
  • Yellowing of the skin
  • Feelings of self-harm

Cautions While Taking Amitriptyline

This drug (amitriptyline) is generally not recommended in pregnancy and breastfeeding mothers.

Amitriptyline should be used with caution with opioid medicines like morphine, and oxycodone because it can increase the risk of respiratory depression (breathing problems).

Withdrawal Symptoms Of Amitriptyline For Pain

Like all antidepressant drugs, you may experience withdrawal symptoms when stopping amitriptyline doses after a long period of consumption. The symptoms are generally bearable. Withdrawal symptoms of amitriptyline include:

  • dizziness/headache
  • Nause/vomiting/diarrhoea
  • Psychological symptoms (mood swings)
  • Flu-like symptoms


Amitriptyline is a tricyclic antidepressant that is FDA approved for depression treatment. When inside the body, amitriptyline upregulates the levels of serotonin (a neurotransmitter) in the nervous system which is associated with pain regulation. The effect of this pumped-up production is strong analgesia. This is why amitriptyline is utilized to reduce different types of pains including arthritis pain, nerve pain (neuralgia, sciatica, etc.), back pain, fibromyalgia, migraine, etc. People also use it to manage sleep disorders and insomnia. When compared with common OTC drugs, amitriptyline performs well. The drug is best suited for the management of fibromyalgia, nerve pain, and migraines. Amitriptyline usage is limited due to the side effects (dry mouth, constipation, dizziness, and heart problems). Like all anti-depressants, the withdrawal effect is seen after chronic usage. It should be avoided by pregnant ladies, and breastfeeding mothers. This particular drug should be cautiously used with opioid medicines due to an increased risk of respiratory depression.

Frequently Asked Questions

Is amitriptyline good as a painkiller?

Amitriptyline is primarily categorized as an anti-depressant, which may also be used as a pain killer. However, the pain relief by Amytyprine is achieved by taking lower doses of the drug and may not show effects immediately. Instead, the individuals may be recommended to take this for the long term. The effects are seen within a few weeks. 

What type of pain does amitriptyline help?

Since amitriptyline does not show its effects immediately, it cannot be used for acute pain. This is why it is most commonly recommended for chronic pains, which may have a neuropathic origin. However, the doses recommended for the treatment of neuropathic pain are usually lower than those recommended for its anti-depressant effects.

Is 10mg amitriptyline enough for nerve pain?

10 mg is usually the starting dose recommended for amitriptyline, after which it may be increased if the doctor recognizes a need for it. Generally, doses of Amitriptyline between 10 mg to 75 mg are considered adequate for nerve pain.

Is amitriptyline stronger than tramadol?

Even though many studies have not been conducted to compare the effectiveness of Amitriptyline and Tramadol directly, experts believe tramadol is more effective than Amitriptyline for certain kinds of pain. This may include pain from an ischaemic origin. 

Is 5mg of amitriptyline effective?

The starting dose of Amitriptyline for effective pain relief is mainly found to start from a 10 mg dose. These tablets come in 3 concentrations which include 10 mg, 25 mg, and 50 mg. However, it is always advised to consult the doctor, who may recommend the most appropriate dose according to the patient’s condition. 

Is amitriptyline a muscle relaxant?

Amitriptyline may work as a muscle relaxant as it helps rebalance the chemicals in the brain. This can lead to the relaxation of muscles, pain relief, and sleep regulation. However, while it does help in muscle relaxation to some extent, it does not come under the class of muscle relaxants. 



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