Amitriptyline is one of the most popular antidepressants in the UK. Its use is not just restricted to the treatment of depression. Amitriptyline is one of the first options considered when a drug treatment is needed to help manage neuropathic pain. This post focuses on the use of amitriptyline for nerve pain. Summary of the post:
- What is amitriptyline?
- What is nerve pain (neuropathic pain)?
- Nerve pain – recommended pharmacological treatment
- Is amitriptyline good (effective) for nerve pain?
- How does amitriptyline work in the management of neuropathic pain?
- Amitriptyline: common side effects
- Amitriptyline for nerve pain & weight gain
- Is paracetamol or ibuprofen good for nerve pain?
- Nerve pain – alternatives to amitriptyline
What is amitriptyline?
Amitriptyline belongs to an antidepressant group of drugs. More specifically, amitriptyline is classified as tricyclic antidepressant. After sertraline and citalopram, amitriptyline is the third most prescribed antidepressant drug in the UK.
Selective serotonin reuptake inhibitors (SSRIs) such as sertraline and citalopram are regarded as first-line treatment of depression, due to a better safety profile and tolerability as compared to other classes of antidepressant drugs (NICE BNF, 2020). Neither of drugs is used in the management of nerve pain/neuropathic pain.
Although amitriptyline and other tricyclic antidepressants have similar effectiveness in the management of depression, their use is not preferable in the first instance, due to side effects and toxicity risk if an overdose is attempted (ibid).
What is nerve pain (neuropathic pain)?
Nerve pain (neuropathic pain), is a pain which affects the somatosensory (sensory) nervous system. Neuropathic pain is caused by injury or an underlying condition (IASP, 2017). The somatosensory system is composed of sensory neurons (nerve cells), which detect internal signals in the body (stimuli), for example of signals of pain, and convert them into electrical impulses which travel in the body to the brain.
Internation Association for the Study of Pain describes a nerve pain (neuropathic pain) as an umbrella definition for a ‘syndrome’, which is ’caused by different diseases or lesions” (IASP, 2011). Lesions are defined as any irregularities found in the body or apparent injury to the body (nerve damage rather than ), which are usually confirmed by a diagnostic test, for example, a lab test, biopsy or imaging.
Diseases, on the other hand, are known causes of nerve pain, for example, obesity, diabetes, stroke (ibid) or chemotherapy-induced neuropathic pain in cancer patients.
Two aspects of the nerve pain (Cavalli et al., 2019):
- abnormal hypersensitivity to stimuli (hyperalgesia)
- nociceptive responses to non-noxious stimuli (allodynia), which in plain language means sensation/perception of pain to something (stimulus) which does not typically cause pain.
Nerve pain – recommended pharmacological treatment
Several drugs are used in the treatment of neuropathic pain. Some common classes of medications include:
- tricyclic antidepressants (TCAs): amitriptyline belongs to this class of antidepressants
- selective serotonin reuptake inhibitors [(SSRIs): antidepressant class
- serotonin-norepinephrine reuptake inhibitors (SNRIs): antidepressant class
- antiepileptic drugs (anticonvulsant)
- opioid analgesics (tramadol): pain killer
- topical products (creams/gels)
As with all treatment recommendations, NICE looks at the effectiveness of medicines confirmed by available evidence and cost of the drugs. Non-drug treatment, for example, physiological therapies can be considered as an option in the management of nerve pain. However, many factors are taken into account when the treatment plan is discussed with patients, such as the severity of pain, impact on day to day life and possible side effects of medication).
Amitriptyline is one of the first choices in the initial management of neuropathic pain. Other drugs which can be offered as first-line treatment of nerve pain include:
- gabapentin or
A patient who failed to respond to initial medicine or cannot tolerate the drug would be prescribed another medication out of the four drugs mentioned above. The second failure would trigger another change to one of the drugs from the above list.
Opioid analgesics such as tramadol are not recommended as first-line treatment of nerve pain but may be considered as a ‘rescue’ medicine to help with severe pain.
Patients may also be treated with a combination of drugs if one drug fails to control the pain.
Is amitriptyline good (effective) for nerve pain?
The best evidence (in science) comes from the review of all existing studies called systemic reviews. When recommending the treatment for conditions in the UK, NICE, looks at this form of reviews to form the evidence-based medicine approach to the treatment.
Cochrane Collaboration produces systemic reviews and makes evidence-based recommendations.
Cochrane reviewed the evidence for the use of amitriptyline in nerve pain (neuropathic pain) by looking at all clinical trials, scientific papers and other reviews. In total, 17 studies were reviewed on the use of amitriptyline in neuropathic pain.
What was the outcome of the review (Moore et al., 2015)?
- Most studies, which looked at the effectiveness of amitriptyline in the treatment of neuropathic pain were small (the number of participants) and old.
- Amitriptyline probably does not work for nerve pain due to cancer or HIV.
- Amitriptyline does work for other types of nerve pain, but not with certainty.
- As a ‘best guess’ may provide neuropathic pain relief in about 1 in 4 patients when compared to no treatment (a dummy pill).
- 1 in 4 patients reported at least one side effect caused by the treatment with amitriptyline.
- Key message: amitriptyline may provide good pain relief from nerve pain; however, in a small number of people. Most people will not work for most people.
How does amitriptyline work in the management of neuropathic pain?
The exact mechanism of action by which amitriptyline helps to control nerve pain is not fully known. However, it is known that amitriptyline can act as a local anaesthetic (Sudoh et al., 2003) and additionally may affect the immune system which plays a big part in neuropathic pain (Fornasari, 2017). Tricyclic antidepressants may block specific receptors in the spinal cord (called NMDA receptors), which play a role in pain transmission (Kremer et al., 2016).
The mechanisms of action described above are different from the mechanism responsible for amitriptyline’s antidepressant effect. Amitriptyline bocks block the reuptake of serotonin and norepinephrine in the brain (increasing their concentration), which is the main driver for an antidepressant effect. Low concentration (amount) of both neurotransmitters is associated with depression.
Amitriptyline: common side effects
Tricyclic antidepressants have many common and very common side effects associated with their use. A group of side effects known as ‘anticholinergic’ are linked with tricyclic antidepressants, including:
- Dry mouth
- Sexual disfunction
- Weight gain
- Urinary retention (inability to empty the bladder completely)
Other very common and common side effects for amitriptyline include:
|Aggression||Confusion, decreased libido & agitation.|
|dizziness, drowsiness,||Mydriasis: dilation of pupils|
|Tremor||Atrioventricular block, bundle branch block.|
|Headaches||Orthostatic hypotension: drop of pressure when one stands up, causing dizziness, sometimes fainting|
|Accommodation disorder: problems with eyesight focus||Excessive sweating|
|Palpitations, tachycardia (increased heartbeats)||Erectile disfunction|
|Congestion||Changes in bladder control and urination (frequency)|
|Dry mouth, constipation, nausea||Fatigue|
Adopted from: Amitriptyline 10mg Film-coated Tablets – SmPC (2020)
Amitriptyline for nerve pain & weight gain
Weight gain is a common side effect listed for amitriptyline. Treatment with antidepressant drugs is associated with ‘a sustained increase in the risk of weight gain’, not just for amitriptyline or the class of drugs it belongs to.
Long term administration of a low dose of tricyclic antidepressants (amitriptyline) can cause a significant weight gain. Increased weight gain leads in many cases to the discontinuation of the treatment. When treatment is stopped with amitriptyline, significant weight loss usually occurs (Berken et al., 1984).
Is paracetamol or ibuprofen good for nerve pain?
Paracetamol or ibuprofen, common painkillers available over the counter are generally not useful to manage neuropathic pain. Neuropathic pain is caused by damage to nerves as opposed to the damage resulting from the injury (for example a cut). Pain associated with both injuries is transferred to the brain by ‘different pain messages’ (Moore et al., 2015), hence lack of effectiveness from common analgesics.
Nerve pain – alternatives to amitriptyline
As I in previous paragraphs, patients are unlikely to get any benefit from over the counter treatment with analgesics such as paracetamol, ibuprofen (or combination of both) or codeine (see over the counter co-codamol).
Prescription-only medicines are the mainstream in the management of nerve pain (list included in the early part of the post).
Other treatment options that may be beneficial in neuropathic pain include:
- Capsaicin (for example, capsaicin patches): High-concentration of capsaicin (not available over the counter) may provide some pain relief in some types of nerve pain (Derry et al., 2017). Two capsaicin creams are licensed in the UK for the management of neuropathic pain: Zacin cream, Axsain cream, both are prescription-only medicines. Prescription-only capsaicin patch licensed for the management of peripheral neuropathic pain in the UK is called Qutenza cutaneous patch.
- Lidocaine patch: may provide benefit in some patients group, when other therapies, including oral drugs, may have questionable safety and tolerability (Sommer & Cruccu, 2017). Lidocaine is a local anaesthetic, commonly used in the UK in skin numbing products. In the UK, lidocaine patch is licensed for the management of nerve pain caused by post-shingles infection.
Amitriptyline is one of the first-line drugs used to relieve nerve pain. Existing evidence suggests that a small number of people benefit from the treatment for amitriptyline; however, in this group of patients, amitriptyline may be effective in controlling neuropathic pain. Treatment with amitriptyline is associated with many common side effects, including weight gain.
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