Major depressive disorder (MDD) is a chronic, disabling condition with a wide range of symptoms, including core mood symptoms of depression and anxiety, cognitive and behavioral deficits, and somatic/physical disturbances. Approximately two-thirds of patients with depression experience physical pain symptoms (e.g. headache, neck and back pain, abdominal pain, diffuse musculoskeletal pain). Pain as a symptom of depression, often has a negative impact upon other depressive symptoms (for example, it may induce or exacerbate low energy, sleep disturbance, and anxiety), adherence to medication, and obtaining adequate therapy. Therefore, pain inşuences both the course of depressive illness and the treatment outcome. Also the severity of pain is found to be a strong predictor of poor response and health-related quality of life. Impairments in social and occupational functioning may increase when depression and pain coexist. Patients who fail to achieve remission after antidepressant therapy are more likely to suffer residual pain and other physical symptoms compared with remitted patients.
The close relationship between pain and depression, and the growing evidence of a connection between treatment outcomes in these conditions, suggests that maximal patient benefit may result from treatments which effectively address both emotional and physical symptom domains. Therefore, treatments that address both depression and pain are highly desirable. Neurobiological evidence suggests that mood and chronic pain are connected via serotonin and noradrenaline neurotransmitter pathways. Serotonin and norepinephrine play a key modulating role in pain mechanisms in the central nervous system. Serotonin modulates both descending inhibitory and facilitatory pathways and thus exerts both an antinociceptive and a pronociceptive effect. Noradrenaline, however, typically acts centrally in an antinociceptive manner, exerting its effects via a-2-adrenoreceptors in the descending antinociceptive pathways.
Efficacy for treating pain is best established for tricyclic antidepressants. But through the last decade, antidepressant medications, particularly selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine reuptake inhibitors (SNRIs), are widely used in the management of MDD. SSRIs are often favored in practice because of their tolerability and safety. However, their efficacy in pain is thought to be relatively weak. On the other hand the mechanism of SNRIs has been hypothesized to confer analgesic effects independent of antidepressant action. Evidence suggests that potentiation of both serotonin and norepinephrine is required for effective analgesia; drugs that inhibit only one of these systems (particularly serotonin) appear to have a limited effect. Whether antidepressants relieve pain through direct analgesic effects or indirectly through antidepressant action is still under discussion. There may be a close association between analgesic and antidepressant effects and pain relief may be secondary to mood improvement.