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Some antidepressants may bring relief to a handful of pain conditions
Roger Selvage 9084

Some antidepressants may bring relief to a handful of pain conditions

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Sonya Collins

Diagram of patient suffering from back pain.

Chronic pain is common and debilitating, and its treatment continues to present challenges to the medical community. Research has shown that some antidepressants may have pain-relieving properties and might offer a potentially safer alternative to existing treatments for pain. But the benefits of these drugs, which include many drug classes, seem to be more apparent in some conditions than in others, and not all drug classes get the same effects.

New research published February 1, 2023, in the BMJ examines the nuances of antidepressants’ effects on pain. The research, which was an analysis of 26 systematic reviews, included 156 unique trials and more than 25,000 participants. The reviews evaluated the efficacy of 8 antidepressant classes in the treatment of 22 pain conditions, including both chronic and acute pain, to draw 42 distinct comparisons.

“We found that some, but not all, antidepressants worked for 9 conditions,” said Giovanni Ferreira, PhD, a research fellow at the University of Sydney in Australia and one of the lead study authors. “They offered more pain reduction than placebo.”


The majority of reviews that found antidepressants offered more pain relief than placebo involved SNRIs. The strongest evidence for these drugs was in the treatment of chronic back pain, postoperative pain (typically for orthopedic surgery), fibromyalgia, and neuropathic pain.

Researchers work with multiple theories as to how SNRIs might bring about these effects. A 2009 review of SNRIs for pain control published in the December issue of Current Pharmacology, for example, noted that SNRIs, particularly in fibromyalgia and neuropathy, may enhance descending inhibition of centrally sensitized pain.

“There’s a lot of assumptions behind the mechanism of action of antidepressants in general, not just for pain,” Ferreira said. “When you transport [those assumptions] to the pain field, there is even less certainty.”


The analysis found that TACs were only more effective than placebo in pain related to irritable bowel syndrome, neuropathic pain, and tension-type headache. On the other hand, many of the reviews that Ferreira and colleagues examined showed that this type of antidepressant was ineffective against the type of pain under investigation—or that evidence was lacking.

“The number of conditions for which tricyclic antidepressants were either ineffective or lacking evidence was interesting since these are typically the most commonly prescribed for pain,” Ferreira said. “I think there needs to be some discussion around the value of these drugs.”


The researchers found low-certainty evidence for SSRIs in the treatment of depression and comorbid chronic pain. The majority of studies that showed that antidepressants were not effective for pain involved SSRIs. They were found ineffective for back pain, fibromyalgia, functional dyspepsia, and non-cardiac chest pain.

Questions remain

While the review demonstrates pain conditions for which certain antidepressants may be more effective than placebo, the implications for this are unclear.

Most of the reviews included in the analysis were sponsored by the pharmaceutical industry. “Those tend to be a little more optimistic than independently done studies,” said Ferreira.

Ferreira also notes that his research doesn’t look at just how much pain relief antidepressants provide and whether patients would be willing to tolerate the adverse effects.

“Our study doesn’t make a judgment as to whether the effects will be clinically meaningful for patients,” Ferreira said. “Patients have very different experiences living with these pain conditions, so we don’t want to delve too much into what’s meaningful and what’s not. That’s for the patient and clinician to decide.”

The study, he says, does not provide sufficient data to change clinical practice.

“I would like our study to start conversations, not necessarily change prescribing patterns,” he said. “We don’t want to make the same mistakes we’ve made with other drugs for pain relief, being overly optimistic and jumping on the bandwagon just prescribing pain medications and forgetting about everything else that works for pain as well.” ■



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