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Antidepressants

Antidepressant medicines work to treat depression by increasing levels of certain chemicals in the brain known as serotonin and norepinephrine. It is thought that these chemicals are also involved in pain response. As a result, antidepressants can help reduce pain in people with chronic pain conditions.
 
It is important to point out that using an antidepressant to treat pain does not mean that the pain is due to depression, or is "all in your head." In fact, antidepressants work to treat pain even in people who are not depressed.
 
The two conditions are often linked, however, such that people who live with chronic pain have an increased risk for developing depression, and depression is known to make symptoms of chronic pain worse. Therefore, antidepressants may help with chronic pain in two ways -- by treating pain directly, and by improving depression, which can further contribute to pain relief.
 
Not all antidepressant medicines are equally effective at relieving pain. The antidepressant classes known to be most effective include tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).
 
Tricyclic Antidepressants
Tricyclic antidepressants have been shown to relieve chronic pain in clinical studies, especially neuropathic pain (pain due to nerve damage). Of the TCAs, amitriptyline (Elavil®) has been studied the most for chronic pain relief. However, other TCAs are also commonly used, including desipramine (Norpramin®), doxepin (Sinequan®, Silenor®), imipramine (Tofranil®, Tofranil PM®), and nortriptyline (Pamelor®). Interestingly, the doses of TCAs used to treat chronic pain are often much lower than the doses used to treat depression.
 
Tricyclic antidepressants work better for some types of chronic pain than others. They tend to be more effective for treating neuropathic pain, such as postherpetic neuralgia (pain that occurs after an outbreak of shingles) or diabetic nerve pain (diabetic peripheral neuropathy), and migraine headaches
 
Serotonin-Norepinephrine Reuptake Inhibitors
SNRI medicines include levomilnacipran (Fetzima™), duloxetine (Cymbalta®), desvenlafaxine (Pristiq®), milnacipran (Savella®), and venlafaxine (Effexor®, Effexor XR®). Like TCAs, they are quite effective at treating neuropathic pain and fibromyalgia. They may also be beneficial for treating other types of pain.
 
In addition to depression and anxiety, duloxetine (Cymbalta) is approved to treat fibromyalgia, diabetic nerve pain, and chronic musculoskeletal pain due to osteoarthritis and chronic lower back pain. In clinical studies, Cymbalta reduced pain in people with these conditions.
 
Milnacipran (Savella) is unique in that it is the only SNRI not approved to treat depression. It is approved by the FDA to treat fibromyalgia. In clinical studies, the drug was shown to reduce pain and improve function in people with this condition.
 
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