Treatment of Pain with Antidepressants

Abstract

INTRODUCTION Chronic pain can result in impairments in quality of life, mood, sleep and cognition 1-5. A high degree of comorbidity often exists between chronic pain and psychiatric disorders, including depression and anxiety, and the coexistence of depression and chronic pain may result in increased difficulties in treating both conditions 5-9. In the relationship between depression and pain, it appears that one can influence the development of the other, i.e., major depression can be a strong predictor of subsequently developing pain and vice versa 9. There is still considerable uncertainty about the reasons for the co-occurrence of pain and depression, although this is an active area of research 5,10-12. Patients experiencing chronic pain are often treated with antidepressants 13-18. Most of the antidepressants produce increased functional availability of the biogenic amines noradrenaline (NA) and/or 5-hydroxytryptamine (5-HT, serotonin) 19,20 , and there is now considerable evidence also implicating GABAergic and glutamatergic mechanisms in the antidepressant effects of these drugs 21-23. Interestingly, these four neurotransmitter systems also appear to be involved in the development and/or modulation of pain 24-30 , suggesting common mechanisms for the development of depression and chronic pain. However, while selective serotonin reuptake inhibitor antidepressants (SSRIs) are used frequently in treatment of depression, they are not as effective as tricyclic antidepressants (TCAs) or serotonin-noradrenaline reuptake inhibitor antidepressants (SNRIs) for most chronic pain conditions 9,14,15,31. Since monoaminergic systems are involved in both depression and chronic pain, it is not surprising that antidepressants have been used frequently for treating chronic pain. However, it should also be noted that many antidepressants have a true analgesic effect in that they are effective at reducing pain in people without depression 5,10,13,14. Pain conditions in which antidepressants are used for treatment include irritable bowel syndrome, central pain syndrome, arthritis, fibromyalgia, low back pain, migraine, d i a b e t i c n e u r o p a t h y, c h e m o-i n d u c e d neuropathies and postherpetic neuralgia (shingles-associated pain) 5,10,14,16,17. Often these pain conditions are treated with TCAs, which are inhibitors of the reuptake of NA and 5-HT. The relative lack of responsiveness to SSRIs and relative success of TCAs in many chronic pain patients suggest that noradrenergic pathways may be more important in chronic pain than in major depressive disorder. The SNRIs are also reported to be more effective than SSRIs in the management …