Antidepressants for Chronic Pain 4/11/2019

It is not uncommon for a patient with depression to also suffer from chronic pain. Some antidepressants are known to be helpful for depression and anxiety disorders as well as some chronic pain conditions. They have been shown to be helpful in pain states that are a result of neural sensitization rather than somatic or visceral nociception. These include pain associated with neuropathy, fibromyalgia, headache, and irritable bowel syndrome.

Antidepressant effects on pain include direct and indirect pain mitigation, direct by modulation of ascending pain transmission and indirect by modification of potential mood and cognitive amplifiers of pain experiences. There seems to be a role for norepinephrine (NE) and serotonin (5-HT) neurotransmitter systems in pain modulation and pain mitigation. Research has shown that antidepressants that impact both the NE and 5-HT neurotransmitter systems have greater analgesic effects than antidepressants with more specific effects.

The classes of antidepressants that have been shown to be effective for chronic pain conditions include tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). The selective serotonin reuptake inhibitors have not been shown to be as effective for the pain symptoms directly, but can be helpful for depression that occurs as a result of chronic pain in some patients. The TCAs have been used off-label since the 1950s to successfully treat patients with certain pain syndromes but their use is limited because of their concerning side effect profiles. The tertiary TCAs like amitriptyline and imipramine, have shown more promising results because of their effects on NE and 5-HT transmission, compared to the secondary TCAs which primary influence noradrenergic activity. In the class of SNRIs, duloxetine has FDA approval as a treatment for several chronic pain syndromes. Studies have not found venlafaxine to be effective for treating neuropathic pain like duloxetine. This is largely due to the fact that at low doses, venlafaxine primarily affects 5-HT and does not have strong effects on the NE system unless higher doses are achieved.

 With respect to specific pain syndromes, amitriptyline has been found to be useful for diabetic neuropathy and post-herpetic neuralgia in several small studies. In the class of SNRIs, duloxetine has FDA approval to treat diabetic neuropathy. In studies for fibromyalgia, there were similar results. Amitriptyline was found to be helpful for fatigue and pain related to fibromyalgia in small studies. The SSRIs were helpful for depression in patients with fibromyalgia but not for fatigue and pain concerns. The SNRIs duloxetine and milnacipran are FDA approved for the treatment of pain related to fibromyalgia, although in studies these agents did not show clinically significant improvement in sleep problems, improving fatigue and over quality of life measurements. Mirtazapine might have some role in helping with sleep disturbance related to fibromyalgia but it has not been found to be effective for other symptoms of fibromyalgia related to pain and fatigue. It remains unclear from research if antidepressants play a role in the treatment of irritable bowel syndrome and migraines, but these medications are commonly used as treatment in clinical practice. There are some promising results on the effect of the SSRIs on irritable bowel syndrome. Amitriptyline is sometimes used for migraine prophylaxis.

 In conclusion, antidepressant medications can be appropriately used to treat select chronic pain syndromes, even in patients without a co-morbid psychiatric illness. SmartCare provider consultation is available to provide recommendations in specific cases.


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