Antidepressants in Pain Management

Antidepressants were originally developed with the intention of improving symptoms of depression, but some of these medications have been recognized for their ability to relieve chronic pain. In particular, chronic neuropathic pain caused by damage to the nerves in the pain pathways is responsive to some antidepressant medications.

As a result, they have become a frequent treatment option to provide moderate pain relief of chronic pain, particularly when first-line analgesic medications such as paracetamol, ibuprofen or aspirin have failed to provide effective pain relief.

It worth noting that a high proportion of patients with chronic pain also suffer from depression, estimated to be approximately half of all patients with chronic pain. While the dose of some antidepressants for pain relief is lower than for depression, some antidepressant medications may manage both conditions concurrently.


Antidepressants may be indicated to relieve chronic pain caused by a variety of circumstances. This may include pain originating from:

  • Arthritis
  • Diabetic neuropathy
  • Facial pain
  • Fibromyalgia
  • Lower back pain
  • Migraine
  • Multiple sclerosis
  • Pelvic pain
  • Peripheral neuropathy
  • Postherpetic neuralgia
  • Spinal cord injury
  • Radiculopathy
  • Tension headache

Administration with antidepressants is often able to provide moderate pain relief for these conditions, which can increase the quality of life for the patient significantly.

Mechanism of Action

To date, the mechanism of action of antidepressant medications in the relief of chronic pain is not well understood.

It is believed that they can lead to an increase in the concentration of neurotransmitters in the spinal cord, which may help to reduce the signaling of pain. However, this effect can take several weeks to become effective and does not provide immediate relief of pain.

Adverse Effects

There are various adverse effects associated with the use of antidepressant drugs, which vary according to the specific drug used. Some common side effects may include:

  • Nausea
  • Drowsiness
  • Insomnia
  • Dry mouth
  • Blurred vision
  • Increased appetite and weight gain

Additionally, individuals that take antidepressants are at an increased risk of suicide. It is unclear if this is causative or an associated factor, but is an important consideration in the pharmacological choice for pain management.

Antidepressants in Use for Pain Relief

Tricyclic antidepressants (TCAs) such as amitriptyline, clomipramine, desipramine, doxepin, imipramine, and nortriptyline are the most common antidepressants used in the treatment of pain.

These drugs are frequently able to provide moderate pain relief from chronic pain, although may be associated with adverse effects such as drowsiness, weight gain and dry mouth. However, the dose required for pain relief is typically lower than that used for depression and is thus associated with few side effects.

Serotonin and norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine and duloxetine may also help to relieve chronic pain. As these medications are usually used in the same therapeutic doses as for depression, they are a suitable option for patients that suffer from both conditions. This also carries an increased risk of side effects, such as drowsiness, insomnia and elevated blood pressure.

Selective serotonin reuptake inhibitors (SSRIs) such as paroxetine and fluoxetine may also be used in patients with concurrent depression and chronic pain, but appear to have limited effectiveness as a stand-alone pain relief. However, they are thought to increase the analgesic effects of some tricyclic antidepressants when used together.


Further Reading

Last Updated: Aug 23, 2018

Sally Robertson

Written by

Sally Robertson

Sally has a Bachelor's Degree in Biomedical Sciences (B.Sc.). She is a specialist in reviewing and summarising the latest findings across all areas of medicine covered in major, high-impact, world-leading international medical journals, international press conferences and bulletins from governmental agencies and regulatory bodies. At News-Medical, Sally generates daily news features, life science articles and interview coverage.


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