Antidepressant Agents for the Treatment of Chronic Pain and Depression

Michael W. Jann, Pharm.D.; Julian H. Slade, Pharm.D.


Pharmacotherapy. 2007;27(11):1571-1587. 

In This Article

Abstract and Introduction


Depression and painful somatic symptoms commonly occur together. Depression and chronic pain can have devastating effects on a patient's health, productivity, and overall quality of life. When moderate-to-severe pain exists, it can impair patient function while making treatment more difficult or resistant, with increased severity in depressive symptoms and worse outcomes. A variety of chronic pain syndromes exist, including diabetic neuropathy. A high prevalence of patients with chronic pain display depressive symptoms. Treatment for these conditions relies on pharmacologic therapy coupled with diligent, periodic assessments of changes in symptom severity. The link between pain and depression lies in the central and peripheral nervous systems. The brain stem serves as an important connection between the higher brain centers and the spinal cord. In the brain stem, the neurotransmitters serotonin and norepinephrine modulate pain transmission through ascending and descending neural pathways. Both serotonin and norepinephrine are also key neurotransmitters involved with the pathophysiology of depression. Tricyclic antidepressants are effective treatments for pain and depression; selective serotonin reuptake inhibitors provide less benefit. Duloxetine and venlafaxine, which are serotonin and norepinephrine reuptake inhibitors, were shown in clinical trials to alleviate pain and depressive symptoms. Diabetic neuropathy and other chronic pain syndromes were also shown to benefit from duloxetine and venlafaxine. Antidepressants remain fundamental therapeutic agents for depression and anxiety disorders. Their extended use into chronic pain, depression with physical pain, physical pain with or without depression, and other potential medical conditions should be recognized.


Chronic pain syndromes and depression are major medical problems facing our society. Approximately 80% of depressed outpatients who completed self-rating questionnaires reported painful somatic symptoms that included stomach pain, neck and back pain, headache, and nonspecific generalized pain.[1] Among hospitalized patients with depression, 92% reported at least one painful symptom, and 76% reported the presence of multiple painful symptoms.[1] Chronic pain originates from a variety of medical illnesses. Although the term "chronic" can be imprecise, we define it as a time period of at least 3–6 months' duration. Pain can be categorized into three groups: nociceptive (somatic and visceral), neuropathic (central [e.g., stroke], peripheral [e.g., nerve compression by cancer, diabetic neuropathy], or mixed [e.g., postherpetic neuralgia]), and psychogenic. Nociceptive pain occurs when a tissue or organ is damaged by injury or disease. Neuropathic pain is a result of direct damage to the nervous system or spinal cord. Psychogenic pain has no discernible physical source.

Pain is an unpleasant experience, and it is reasonable that its symptoms are closely linked to depression. In a population of patients with various sources of chronic pain, 28% reported at least one depressive symptom and 43% fulfilled the diagnosis for major depression.[1] The frequency of clinical depression in patients with other diseases in which chronic pain is a significant component is staggering and has been reported to be 30–54%.[2]

Other symptoms that overlap both chronic pain and depression are found in anxiety disorders and would be more commonly associated with generalized anxiety disorder. In patients with generalized anxiety disorder, the psychological symptoms of excessive anxiety, constant worries that are difficult to control, feeling on edge, and poor concentration combined with the physical symptoms of fatigue, muscle tension, restlessness, and sleep disturbance can easily lead to depression. Whereas patients with chronic pain can have many symptoms also found in generalized anxiety, sleep disturbance may be one of the most common indistinguishable symptoms among the three categories of chronic pain, depression, and anxiety.[3] It can be difficult for clinicians to discern the origin of these overlapping symptoms that lead to subsequent problems. We examine the relationship between chronic pain and depression and provide a pharmacologic rationale for the efficacy of antidepressants for the treatment of both debilitating conditions. We also discuss the implications of antidepressants that possess both norepinephrine and serotonergic properties that have been shown to be effective in treating chronic pain and depression in clinical studies.


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