Can amitriptyline (tricyclic antidepressant) relieve neuropathic pain?

From the Guidelines

Amitriptyline can effectively relieve neuropathic pain, and it is recommended to start with a low dose of 10-25 mg taken once daily at bedtime, with gradual increases as needed and tolerated, up to 75-150 mg daily. The most recent and highest quality study, published in 2023 1, supports the use of amitriptyline for the treatment of neuropathic pain in diabetes, with two high-quality studies and two medium-quality studies demonstrating its effectiveness. Amitriptyline works by increasing levels of neurotransmitters (serotonin and norepinephrine) in the nervous system, which helps block pain signals and has direct effects on pain pathways. Some key points to consider when prescribing amitriptyline include:

• Starting with a low dose and gradually increasing as needed and tolerated
• Being aware of potential side effects, such as drowsiness, dry mouth, constipation, and dizziness
• Avoiding use in patients with certain heart conditions, glaucoma, urinary retention issues, or those taking MAO inhibitors
• Using caution in elderly patients due to increased sensitivity to side effects
• Tapering the medication gradually under medical supervision if it needs to be stopped. It's also important to note that amitriptyline is just one of several pharmacologic therapies that can be considered for the treatment of neuropathic pain, and the choice of medication should be individualized based on the patient's specific needs and medical history.

From the Research

Amitriptyline for Neuropathic Pain Relief

• Amitriptyline is a tricyclic antidepressant that is widely used to treat chronic neuropathic pain (pain due to nerve damage) and fibromyalgia 2, 3, 4.
• The evidence suggests that amitriptyline can relieve neuropathic pain in some patients, but the effect is not consistent across all studies 2, 3, 4, 5.
• A study published in 2012 found that amitriptyline had a statistically significant benefit in relieving neuropathic pain, with a number needed to treat (NNT) of 4.6 2.
• Another study published in 2015 found that amitriptyline had a moderate to good response in up to two-thirds of patients with post-herpetic neuralgia and three-quarters of patients with painful diabetic neuropathy 3.
• However, a more recent study published in 2022 found that amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin had similar analgesic efficacy in treating diabetic peripheral neuropathic pain 5.

Mechanism of Action

• The mechanism of action of amitriptyline in relieving neuropathic pain is not fully understood, but it is thought to involve the recruitment of noradrenergic descending pathways and the peripheral recruitment of noradrenaline from sympathetic fibers sprouting into dorsal root ganglia 6.
• Amitriptyline may also indirectly act as an anti-proinflammatory cytokine drug, and its therapeutic action requires the opioid system, particularly the mu (MOP) and/or delta (DOP) opioid receptors 6.

Adverse Events

• Amitriptyline is associated with a number of adverse events, including dry mouth, sedation, orthostatic hypotension, and tachycardia 2, 3, 4, 5.
• The risk of adverse events is higher with amitriptyline than with placebo, with a number needed to treat to harm of 4.1 2.
• However, the majority of patients are able to tolerate amitriptyline, and the benefits of treatment often outweigh the risks 2, 3, 4, 5.