Off-label Antidepressant Use for Treatment and Management of Chronic Pain: Evolving Understanding and Comprehensive Review

  • Ivan UritsEmail author
  • Jacquelin Peck
  • Mariam Salisu Orhurhu
  • John Wolf
  • Riki Patel
  • Vwaire Orhurhu
  • Alan D. Kaye
  • Omar Viswanath
Other Pain (A Kaye and N Vadivelu, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Other Pain


Purpose of Review

While clinicians have been using antidepressants for off-label indications in the treatment of chronic pain in recent years, newer studies have proven effectiveness and provided additional mechanistic understanding and defined potential adverse effects. As depression and chronic pain are frequently comorbid conditions, the use of antidepressants has allowed for treatment of both conditions concomitantly in the same patient population.

Recent Findings

The most commonly used antidepressants for chronic pain are tricyclic antidepressants (TCAs), though selective serotonin or noradrenaline reuptake inhibitors and other atypical antidepressants have been shown to be effective at treating chronic pain. In addition to neuropathic pain, bupropion has also demonstrated effectiveness in treating chronic pain caused by inflammatory bowel disease. Selective norepinephrine receptor inhibitors (SNRIs), including duloxetine, serve to suppress neuropathic pain by altering recovery of the noradrenergic descending inhibitory system in the spinal cord. While the direct mechanism of action is largely unknown, TCAs may suppress the noradrenergic descending inhibitory system to produce an antihyperalgesic effect.


The use of antidepressants offers alternative and adjunctive therapy options for patients suffering from chronic pain from various modalities. TCAs, mono-amine oxidase inhibitors, selective serotonin receptor inhibitors, SNRIs, and atypical antidepressants have been shown to have analgesic and sometimes antiinflammatory capabilities that are independent of their mood-stabilizing effects. Further studies are warranted to establish better safety profiles and efficacy of antidepressant use in chronic pain.


Off-label antidepressants Antidepressants Chronic pain TCAs SNRIs SSRIs 


Compliance with Ethical Standards

Conflict of Interest

Ivan Urits, Jacquelin Peck, Mariam Salisu Orhurhu, John Wolf, Riki Patel, Vwaire Orhurhu, and Omar Viswanath declare no conflict of interest. Alan D. Kaye discloses that he is on the Speakers Bureau for Depomed, Inc. and Merck.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ivan Urits
    • 1
    Email author
  • Jacquelin Peck
    • 2
  • Mariam Salisu Orhurhu
    • 3
  • John Wolf
    • 4
  • Riki Patel
    • 4
  • Vwaire Orhurhu
    • 1
  • Alan D. Kaye
    • 5
  • Omar Viswanath
    • 6
    • 7
    • 8
  1. 1.Beth Israel Deaconess Medical Center, Department of Anesthesia, Critical Care, and Pain MedicineHarvard Medical SchoolBostonUSA
  2. 2.Department of AnesthesiologyMt. Sinai Medical Center of FloridaMiami BeachUSA
  3. 3.Department of Anesthesia and Critical Care MedicineJohns Hopkins School of MedicineBaltimoreUSA
  4. 4.School of Medicine - Phoenix Regional CampusCreighton UniversityPhoenixUSA
  5. 5.Department of AnesthesiologyLouisiana State University Health Sciences CenterNew OrleansUSA
  6. 6.Valley Anesthesiology and Pain ConsultantsPhoenixUSA
  7. 7.Department of AnesthesiologyUniversity of Arizona College of Medicine-PhoenixPhoenixUSA
  8. 8.Department of AnesthesiologyCreighton University School of MedicineOmahaUSA

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