Chronic Pain and Depression—Why Antidepressants Treat Both
In the last decade, emerging and persuasive evidence reveals that inflammation may play an important role in the pathogenesis of both clinical depression and chronic pain syndromes.1,2 This common denominator may partially explain why patients with pain are more prone to develop clinical depression and vice versa.
Chronic pain and major depression have a shared neurobiology and appear to have a shared neuroanatomy, with similar disturbances to the hypothalamic-pituitary-adrenal (HPA) axis, autonomic nervous system (ANS), and inflammatory cytokines.3-5
Stress, anxiety, and depression not only provoke emotional distress, but also destabilize the HPA axis.6 Additionally, the ANS is often dysregulated in depression and chronic pain states. Finally, the cell-mediated immune system is also affected, resulting in over-production of inflammatory cytokines and diminished production of anti-inflammatory cytokines.7-9 Interestingly, similar changes also occur in patients with chronic pain. There is growing evidence that these changes (HPA axis, ANS, and cytokine deregulation) play an important role in creating clinical depression and destabilizing an individual's innate pain-regulating system.10,11
Why Antidepressants Act Against Pain
Studies have clearly shown that antidepressants act as anti-inflammatory agents in both depression and chronic pain states.12,13 Antidepressant therapy improves the clinical symptoms of depression and chronic pain and appears to positively impact immune/cytokine deregulations. Research data indicate that antidepressants can reduce levels of inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6.14-16 Other non-pharmacological interventions, such as cognitive-behavioral therapy, yoga, and exercise, interestingly also show the same positive and salutary effects on the immune and cytokine system.17
In addition to anti-inflammatory properties, data clearly show that antidepressants (mostly the tricyclic antidepressants and serotonin–norepinephrine reuptake inhibitors) have antinociceptive properties.18 Multiple studies reveal that even in the absence of depression, these antidepressants have efficacy in multiple chronic pain conditions irrespective of comorbid chronic clinical depression.19
Table 1 reviews various types of antidepressants used for pain management.20-25