Antidepressants get prescribed for chronic pain – but do they work?

Antidepressants are not just used for depression: they’re often prescribed for chronic pain as well.

But according to a new review in the British Medical Journal, these prescriptions might not always be the best idea. While antidepressants were effective at treating some types of pain, there were also plenty of cases where the antidepressants were ineffective or inconclusive.

“Chronic pain is a difficult thing to treat: not a lot of treatments work for most people,” says lead author Dr Giovanni Ferreira, from The Institute for Musculoskeletal Health and the University of Sydney.

“There’s usually a lot of trial and error, people don’t respond to treatments, and there’s a lot of variation in how people respond to what’s available.

“Antidepressants are just one more tool in the clinician’s toolbox to try to address the problem.”

In Australia, the only antidepressant formally approved for treating pain is duloxetine, for nerve pain caused by diabetes. While other countries have more approvals, most antidepressant prescriptions for pain are off-label.

Ferreira and colleagues analysed 26 systematic reviews of antidepressants and different pain conditions, including back pain, fibromyalgia, headaches, postoperative pain, and irritable bowel syndrome.

The reviews, which were all published between 2012 and 2022, covered a total of 25,000 study participants and eight different antidepressant classes.

“This review, for the first time, brings together all the existing evidence about the effectiveness of antidepressants to treat chronic pain in one comprehensive document,” says Ferreira.

“It took us about six to eight months to get all the data.”

The results were mixed.

The data covered 42 distinct comparisons (that is, looking at the efficacy of a specific drug for a specific pain condition).

Of these, only 11 comparisons showed that an antidepressant was effective at treating a pain condition.

Seven of these 11 were serotonin-norepinephrine reuptake inhibitors (SNRI) antidepressants. They were found to work for back pain, knee osteoarthritis, postoperative pain, fibromyalgia, and neuropathic pain (nerve pain).

Tricyclic antidepressants (TCAs), on the other hand, are the most commonly prescribed antidepressant for chronic pain. But there wasn’t much evidence showing they worked.

Read more: Why do antidepressants help treat nerve pain?

The researchers hope that their review will help clinicians to be more targeted in their chronic pain prescriptions.

“A one size fits all approach to thinking of antidepressants for pain doesn’t work,” says Ferreira.

“When we say antidepressants, we’re talking about dozens of different medications. Our review shows that some of these medicines may have a role for some pain conditions, but not for others.”

Antidepressants often have other side effects and can cause withdrawal if someone stops taking them abruptly.

Ferreira says that other pain medications, as well as physiological and psychological treatments and lifestyle changes, should be considered part of the solution for chronic pain conditions as well.

“Obviously, this whole discussion has to be done with a health professional to see what the better option is for that particular patient,” says Ferreira.

“While this article calls for a ‘nuanced’ discussion about antidepressants, it unfortunately lacks a bit of nuance in its conclusions,” says Associate Professor Michael Vagg, director of private pain management practice Pain Matrix and an affiliate associate professor at Deakin University’s School of Medicine.

“It confirms the pre-existing interpretation familiar to specialist pain doctors that for pain with a prominent neuropathic [nerve] mechanism involved, SNRI and TCAs are the best-evidenced choices to trial.

“Limitations in diagnostic labelling of pain conditions, use of obsolete terms like ‘sciatica’ and the complex way that chronic pain is processed have left gaps in the evidence which are well-acknowledged.”

Vagg says there are initiatives underway to research and learn more about how these drugs work with pain.