Antidepressants in Pain Management

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Antidepressants were originally developed with the intention of improving symptoms of depression; however, 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.

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As a result, the use of certain antidepressants has 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 approximately half of the patients with chronic pain also suffer from depression. While the dose of some antidepressants for pain relief is lower than that which is used 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

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

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 these drugs 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 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 who 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 for Postsurgical Pain Relief?

Antidepressants 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 they 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 fewer 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 who 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 stand-alone pain relief. However, these agents are thought to increase the analgesic effects of some TCAs when used together.


Further Reading

Last Updated: May 12, 2021

Sally Robertson

Written by

Sally Robertson

Sally first developed an interest in medical communications when she took on the role of Journal Development Editor for BioMed Central (BMC), after having graduated with a degree in biomedical science from Greenwich University.


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