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

Abstract

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.

Keywords: Antidepressants; Chronic pain; Off-label antidepressants; SNRIs; SSRIs; TCAs.