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Antidepressants for Pain Relief After Surgery: Not Ready for Prime Time

Debra Gordon

Last updated: November 22, 2016 3:32 pm

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You’re having chronic pain and the painkillers your doctor prescribed just aren’t working. This time, however, she gives you a prescription for an antidepressant. “But I’m not depressed!” you say. “Try them,” she says. “I think they’ll work.”

She could be right. Antidepressants are often prescribed for chronic pain, particularly neuropathic pain, fibromyalgia, low back pain, and headaches. Most are prescribed off label, but desipramine (Norpramin), amitriptyline (Elavil) and duloxetine (Cymbalta) are approved to treat some forms of chronic pain. In addition, several large reviews of published studies find that certain antidepressants, particularly tricyclic medications such as Elavil and Norpramin, are quite effective in relieving neuropathic pain like diabetic neuropathy.

However, antidepressants are increasingly being prescribed off label for post-operative pain, where there is less evidence. As the authors of a recent review article wrote, “studies on antidepressants for postoperative pain have generated, possibly premature, enthusiasm for this potentially new indication.”

Antidepressants and Pain

We don’t know exactly how antidepressants work to reduce pain, but it is likely related to their ability to alter amounts chemicals in the brain and spinal cord called neurotransmitters. These help cells in the brain and spinal cord communicate with each other, so changing their activity could short-circuit pain signals.

What the Evidence Shows

However, they may not be as effective with acute pain, like that occuring after an operation. An international group of doctors conducted an extensive review of all published studies on the use of antidepressants for postoperative pain. The 16 studies they analyzed involved nearly 1,000 participants, and evaluated the effectiveness of the antidepressants amitriptyline (Elavil), bicifadine (which is being investigated as a pain treatment), desipramine (Norpramin), duloxetine (Cymbalta), fluoxetine (Prozac), fluradoline, tryptophan (Tryptan), escitalopram (Lexapro), and venlafaxine (Effexor) for treating acute pain after surgery and reducing chronic post-operative pain.

The researchers found just eight of 16 studies showed that the antidepressant was better than a placebo at reducing acute pain after surgery; and just one of three showed it was better at preventing postoperative chronic pain. Most of the studies were also extremely small. One study of escitalopram, in which patients started on the drug two to three weeks before heart surgery and continued taking it for six months, also found a significantly higher rate of side effects, including diarrhea, constipation, nausea, shivering, sedation, and tingling.

The researchers concluded that “there is currently insufficient evidence to support the clinical use of antidepressants—beyond controlled investigations—for treatment of acute, or prevention of chronic, postoperative pain.”

Similar review articles also show little benefit of antidepressants to treat low back pain, even though nearly one in four primary care physicians prescribe the drugs for this reason; and in rheumatoid arthritis.

Bottom line: If your doctor prescribes an antidepressant for your pain, ask about the evidence for its use in the type of pain you’re having. If that evidence is weak, you may want to skip it and try something else.