Effectiveness of Antidepressants for Chronic Pain Seriously Questioned

New research finds most of the meds lack evidence that they work. That doesn’t mean they never do, however. Yeah, confusing. Here’s what you need to know.

A large new review of research finds most antidepressants prescribed for chronic pain — including amitriptyline, duloxetine, fluoxetine, citalopram, paroxetine, and sertraline — lack evidence to suggest they work. Some might be effective in some cases, but the evidence just isn’t there for any generalized optimism, and the study raised concerns about long-term safety of the drugs.

“Our review found no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for their safety for chronic pain at any point,” said study team member Tamar Pincus, PhD, a professor of health psychology at UK’s University of Southampton.

The findings, from an analysis of 176 trials involving 28,664 people, were published by the non-profit group Cochrane.

“This is a global public health concern,” Pincus said. “Chronic pain is a problem for millions who are prescribed antidepressants without sufficient scientific proof they help, nor an understanding of the long-term impact on health.”

About 20% of U.S. adults, and a similar number globally, struggle with chronic pain most days or daily.

One antidepressant — duloxetine, sold under the brand names Cymbalta, Yentreve, Drizalma Sprinkle and Irenka — was found to offer short-term pain relief, but “we remain concerned about its possible long-term harm due to the gaps in current evidence,” Pincus said.

Chronic pain becomes mysteriously hard-wired

The new findings are not terribly surprising. Previous research has found most drugs to treat chronic pain, from over-the-counter ibuprofen to highly addictive opioids, prove ineffective for many people or stop working over time.

As one example of the changing thought on treatments, the American College of Rheumatology recommends physical activity and weight loss, above medications, for arthritis, and they stress the importance of seeking medical advice to ensure a targeted, individualized pain-mitigation effort that might include other non-drug therapies.

Vexing any treatment efforts is the fact that chronic pain remains a great big scientific mystery. In many cases, the actual source cause of chronic pain cannot be pinpointed.

While it’s not “in your head,” ongoing chronic pain can change the physical and biological structures in the brain and nervous system, creating signals that are no longer rooted in any injury or other physical problem. And the physical sensations tend to get all mixed up with our thoughts and emotions, creating a tangle of interrelated effects that helps explain why physicians might prescribe antidepressants for pain in the first place.

“The more pain you have, the more anxiety you have, the more pain you have, the more depression, the more catastrophizing, the more fear,” Vania Apkarian, PhD, who runs a pain clinic at Northwestern University’s Feinberg School of Medicine, has explained to me. “All of those things sort of cluster together.”

Pain that should have gone away becomes like a memory, hard-wired in the sensory system, with effects that can even vary significantly based on an individual’s core personality and brain structure, as I explained in this in-depth report:

What the new research means

The new results don’t necessarily mean all of these antidepressants never work for anyone, other experts noted. For some of the drugs, there’s not enough research to make a call, and for others the existing research is of low quality. And given the many origins and causes of chronic pain, each person’s treatment needs to be individualized, they said.

Pain-treatment experts who weren’t involved in the review spoke to its broader meaning.

“This well-conducted review adds to the substantial evidence we now have that shows that the use of medicines to treat long-term pain is disappointing,” Cathy Stannard, who heads up guidelines on chronic pain treatment for the UK’s National Institute for Health and Care Excellence (NICE) said in a statement from the UK’s nonprofit Science Media Center.

“The systems that regulate mood and pain overlap considerably, meaning some antidepressants can provide pain relief,” said Ryan Patel, PhD, a neuroscience researcher at King’s College London. “What this comprehensive analysis demonstrates is that when clinical trials are designed poorly under the assumption that everyone’s experience of pain is uniform, most antidepressants appear to have limited use for treating chronic pain.”

Gavin Stewart, a statistician at Newcastle University and co-author of the Cochrane review, had a strong message for NICE and the U.S. Food and Drug Administration:

“We are calling on governing health bodies NICE and the FDA to update their guidelines to reflect the new scientific evidence, and on funders to stop supporting small and flawed trials,” Stewart said.

What should you do?

If you take any pain medication on an ongoing basis, it’s vital to check in with a healthcare provider and, as many other experts advise, ask a lot of questions about any medications you are on, including whether they’re even working, and whether they might react negatively with other meds you might take.

Most importantly, ask whether alternative lifestyle-centered approaches could help alleviate your pain and allow you to reduce or eliminate medications. Because, as I wrote recently, many experts say prescription medications are wildly overprescribed. More than 80% of Americans 50 and older are on at least one prescription drug, and 28% take five or more. Millions of these people taking more medications than they need, including drugs that no longer work for them, experts say.

Patel answered an immediate question many people might have now.

“If you are someone living with chronic pain and taking antidepressant drugs to manage your symptoms, the best advice is to continue taking them if they work for you,” he said. “Even when the cause of chronic pain is the same, the biological changes that occur in the nervous system are varied, and so it is no surprise that pain presents differently from person to person, and not everyone will respond to the same drugs.”

Note: This article was updated May 10 to include additional background information.

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