Amitriptyline for Pain

What is Amitriptyline?

How Does it Work?

Amitriptyline is a tricyclic antidepressant that can be used to treat pain. Amitriptyline has many different effects on the body. With regards to pain, it acts on the brain and throughout the body to alter the actions of naturally occurring chemicals involved in pain pathways.1 As is referred to in it's drug class name, amitriptyline is also used to treat depression. 

What Kinds of Pain Can it be Used For?

Antidepressants, such as Amitriptyline, have been used to treat chronic pain for many years and have been tested in a number of clinical trials.2 Amitriptyline is mainly prescribed in the management of neuropathic pain, also known as nerve pain. This is pain that originates from damage to nerve tissue. It can present as burning, shooting, and stabbing pain which keeps you awake at night. There are a number of different causes of neuropathic pain:1,3  

  • Diabetes - painful diabetic neuropathy
  • Shingles
  • Amputation
  • Stroke or spinal cord injury
  • Trigeminal neuralgia - sudden, severe facial pain
  • Pain after surgery or an accident

Neuropathic pain is different from other chronic pain conditions, such as inflammation in rheumatoid arthritis. In turn, this is why common painkillers, like ibuprofen and paracetamol, are not often given by your doctor when treating neuropathic pain.4 

Who Can Take Amitriptyline, and Who Cannot?

Most adults over the age of 18 can take amitriptyline. There are some conditions in which it can be prescribed for children, however, it is not recommended.

Amitriptyline is not suitable for specific individuals that fit into the following criteria:

  • Any previous allergic reaction to amitriptyline or any of the other ingredients in the formulation.
  • A  heart problem, or a recent heart attack.
  • Individuals already using a medicine within the drug class – Monoamine Oxidase Inhibitor
  • Severe liver disease
  • In children under 6 years of age

If any of the following situations or conditions apply to you, a doctor should be consulted before taking amitriptyline:5 

  • Thyroid issues
  • Elderly patients
  • Imminent or emergency surgery
  • Epilepsy
  • Signs of paranoid behaviour
  • Any gastrointestinal disease diagnosis
  • A history of suicidal thoughts
  • Type 1 or type 2 diabetes
  • Individuals already prescribed a medicine known as a selective serotonin reuptake inhibitor (SSRI); the most common of these are fluoxetine and citalopram.
  • Any changes in urination habits
  • Pregnancy or breastfeeding (see section - Pregnancy and Breastfeeding)

Dosage and Duration of Treatment

Amitriptyline is available in tablet form as well as liquid form.

  • Tablets come in 10mg, 25mg and 50mg strengths.
  • Liquid form comes in 10mg, 25mg and 50mg per 5ml spoonful.6

In its use as pain relief, patients are usually given the strength which provides the best effects, where the side effects are still tolerable. In general, the lowest dose for the shortest time is recommended. The doses used to aid patients with pain are usually lower than those used in the treatment of depression. Ultimately, this can reduce the chances of unwanted side effects.3 

Adults:

  • The initial dose for adults is 10mg daily
  • The recommended daily doses are 25mg- 75mg in the evening.

Dosing above 100mg is not recommended, however, each individual is dosed based on their response to the medicine - so higher doses may be seen in practice. Taking amitriptyline in the evening is recommended as it helps reduce the sedative effects during the day.

The dose can be taken as follows:

  • Once a day
  • Or in two separate doses

A single dose of 75mg at any one time is not advised.

Pain relief usually starts to take effect between 2 and 4 weeks after taking the tablets.5,7 

Side Effects

The most commonly reported side effects of amitriptyline are:

  • weight gain
  • gastrointestinal symptoms such as; constipation, dizziness, headache, and drowsiness
  • dry mouth (xerostomia)5,6

The following more severe side effects have been reported:

  • Orthostatic hypertension, dizziness, and sedation.
  • Irregular heartbeats
  • Blurred vision, urinary retention, acute angle glaucoma
  • Sedation, increased appetite, weight gain, confusion, and delirium.
  • Abnormalities in liver function tests
  • Increased risk of bone marrow suppression and fractures.
  • Mania - It rarely induces mania at antidepressive doses. The main risk factors are a history of bipolar disorder and a family history of mania.5,7

Due to the variety of side effects, there are a number of limits that need monitoring in patients taking this medicine in high doses:

  • Body Mass Index
  • Liver function test
  • Thyroid function test.
  • Patients with a history of heart issues over the age of 50 should undergo a baseline electrocardiogram (ECG).
  • Individuals should be monitored for unusual behavioural changes e.g. Mania and depression, with a focus on the first two months after starting medication.5

N.B: If you do notice any major changes in your mental or physical health after starting treatment with Amitriptyline, you must consult your doctor immediately. 

Coping with Side Effects

  • Dizziness - drink plenty of water and try not to stand too quickly after sitting down for long periods.
  • Drowsiness and tiredness - it is better to take this medicine in the evening and to reduce the amount of alcohol you consume. If you feel this way, you shouldn't drive, operate machinery, or cycle.
  • Dry mouth - try sucking on sugar-free sweets or chewing sugar-free gum.
  • Headaches - ensure you drink the RDA of 2 litres of water and reduce alcohol content. If this symptom persists then paracetamol or ibuprofen can be taken but on the advice of your doctor or pharmacist. If the headaches last longer than 7 days and/or worsen, then report this to your doctor immediately.
  • Difficulty urinating - do not force the flow of urine. Try to relax, or try to go again later. If you are unable to urinate at all then consult your doctor immediately.
  • Constipation - eating more fibre such as fruits and vegetables can help. Try to drink the RDA of 2 litres of water per day or other drinks that are sugar-free. Incorporating exercise into your daily routine can also help with constipation.6

Pregnancy and Breastfeeding

Amitriptyline is not recommended during pregnancy. If, however, its use is clearly needed, the prescriber will only permit it after careful consideration of the risks and benefits. In the final weeks of pregnancy, after chronic use, the baby may experience withdrawal symptoms. This may be in the form of loud crying, irritability, constipation, and poor drinking.

Amitriptyline and its breakdown products have been found in breast milk at low doses. In turn, it is not recommended in breastfeeding as an effect on the baby cannot be excluded. If it is considered a necessary treatment, a doctor can be consulted for advice and a possible alternative.7 

Possible Interactions with Other Medicines

Amitriptyline and several other drugs can affect each other. This increases the chances of unwanted effects. Thus, it is essential that you inform your doctor of any new medicines you might start while taking amitriptyline. Advice can also be sought from a pharmacist about any new concerns when starting amitriptyline with other medicines.6,7 

The following is a list of medicines that can only be taken with amitriptyline on the advice of a doctor:

  • Morphine, codeine, and oxycodone; these can all increase the drowsy effects of amitriptyline.8
  • Antidepressants, specifically MAOIs (monoamine oxidase inhibitors) such as; selegiline, isocarboxazid, and tranylcypromine.
  • Alcohol can increase the drowsy effects of amitriptyline, and therefore should be avoided or consumption reduced, especially in the first few weeks of treatment.

Summary

Amitriptyline belongs to the tricyclic antidepressant group of drugs. Among its many uses, it is widely prescribed for pain relief - specifically neuropathic pain. This kind of pain is caused by damage to the nervous system and is not managed by common painkillers such as paracetamol.

Amitriptyline comes in a variety of different strengths. The dose and length of treatment are decided by your doctor depending on how well your pain is controlled and how little side effects you experience. In general, the lowest dose for the shortest time is preferred. If a higher than normal dose is needed, a number of measures will be monitored by your prescriber; body weight, behaviour changes, and liver and kidney function.

Due to the way this drug works in the body, it has a number of side effects. However, there is information available to help you manage these symptoms.6 Amitriptyline is not advised in pregnancy and breastfeeding, however, if a doctor thinks it is necessary, it can be prescribed and the mother and baby will be monitored.

Amitriptyline can affect other medicines so it is important that any new medicines being taken with this drug are reported to your doctor. 

References

  1. Honore P, Jarvis MF. Therapeutic areas I: Central Nervous System, Pain, Metabolic Syndrome, Urology, Gastrointestinal and Cardiovascular. Comprehensive Medicinal Chemistry II 2007;6:327-349.
  2. Mc Mahon S, Koltzenburg M, Tracey I, Turk DC. Wall and Melzack's Textbook of Pain. Saunders; 2013.
  3. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015 Jul 6;2015(7):CD008242.
  4. Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, et al. Neuropathic pain. Nat Rev Dis Primers. 2017 Feb 16;3:17002. 
  5. Electronic Medicines Compendium. Summary of Product Characteristics Amitriptyline 10mg tablets (Internet), 2022 (Cited 23 June 2022). Available from: https://www.medicines.org.uk/emc/product/5698/smpc#gref 
  6. NHS UK. Amitriptyline for pain and migraine (Internet). 2020 (cited 23 June 2022). Available from: https://www.nhs.uk/medicines/amitriptyline-for-pain/ 
  7. National Institute for Health and Care Excellence. Amitriptyline hydrochloride (Internet) 2022 (cited 23 June 2022). Available from: Amitriptyline hydrochloride | Drugs | BNF | NICE
  8. Botney M, Fields HL. Amitriptyline potentiates morphine analgesia by a direct action on the central nervous system. Ann Neurol. 1983 Feb;13(2):160-4.
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Danielle Ferrie

Masters of Pharmacy - MPharm, University of Strathclyde, Scotland

Danielle is a Locum Pharmacist with strong business acumen having exposure to clinical and management roles between the hospital and community sectors.
She has several years of experience as a GPhC registered Pharmacist as well as an EFL Teacher working with University lecturers on editing articles.

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