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Study questions the effectiveness of antidepressants used for chronic pain

An international team of researchers, including academics from the University of Warwick, has found that although some classes of antidepressants are effective in treating certain pain conditions in adults, others were either not effective or featured an unknown level of effectiveness.

Between 1/3 and 1/2 of the UK’s population is affected by chronic pain, but its treatment is often suboptimal. Commonly used medicines, including antidepressants, are prescribed to help manage chronic pain, though knowledge about the extent of their benefits is uncertain, and in some cases, they could cause harmful side effects.

“We need to work harder to help people manage their pain and live better” – Professor Martin Underwood

The researchers brought together existing literature and studies on the safety and effectiveness of antidepressants in the treatment of chronic pain, distilling evidence from over 150 clinical trials. In the article, published in The BMJ, the researchers suggest clinicians need to consider all the evidence before deciding to prescribe antidepressants for chronic pain management.

Professor Martin Underwood from the University of Warwick, a co-author of the paper, said: “There is a role for antidepressants in helping people living with chronic pain, however, this is more limited than previously thought. Antidepressants may have unpleasant side effects that patients may wish to avoid. We need to work harder to help people manage their pain and live better, without relying on the prescription pad.”

The review examined 26 systematic reviews from 2012 to 2022 involving over 25,000 participants. This included data from eight antidepressant classes and 22 pain conditions including back pain, fibromyalgia, headaches, postoperative pain, and irritable bowel syndrome. Serotonin-norepinephrine reuptake inhibitors (SNRI) antidepressants such as duloxetine were found to be effective for the largest number of pain conditions, such as back pain, knee osteoarthritis, postoperative pain, fibromyalgia, and neuropathic pain (nerve pain). By contrast, tricyclic antidepressants, such as amitriptyline, are the most commonly used antidepressant to treat pain in clinical practice, but the review showed that it is unclear how well they work, or whether they work at all for most pain conditions.

“The findings suggest that a more nuanced approach is needed when prescribing antidepressants for pain” – Dr Giovanni Ferreira 

Lead author Giovanni Ferreira, from the Institute for Musculoskeletal Health at the University of Sydney, said: “Recommending a list of antidepressants without careful consideration of the evidence for each of those antidepressants for different pain conditions may mislead clinicians and patients into thinking that all antidepressants have the same effectiveness for pain conditions. We showed that this is not the case.

“Some antidepressants were efficacious for some pain conditions; however, efficacy appears to depend on the condition and class of antidepressant. The findings suggest that a more nuanced approach is needed when prescribing antidepressants for pain.”

An accompanying editorial, also published in The BMJ, said that this work adds to growing evidence that many medications prescribed for pain – not just antidepressants – are only modestly effective.

In the piece, Cathy Stannard, of the UK National Health Service, and Colin Wilkinson, pain patient and consultant at the Centre for Pain Research at the University of Bath, wrote: “Their findings suggest that for most adults living with chronic pain, antidepressant treatment will be disappointing. This is important given emerging concerns about increases in the prescribing of antidepressants and the challenges patients describe when trying to withdraw from treatment.

“Clinicians continue to prescribe medicines for which the evidence is poor because they observe that some people respond to them, albeit modestly. But all medicines carry risk of harm and there are other, less potentially harmful options more likely to help people to live well with pain.”


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