Majority of Antidepressants Used for Treatment of Chronic Pain Lack Sufficient Efficacy, Safety Data


A new meta-analysis found duloxetine to be the only commonly prescribed medication that was effective.

Nearly 1 in 5 people globally are affected by chronic pain, which can have a negative impact on well-being, physical ability and quality of life.1

Antidepressants have long been considered important tools in treating the condition, even when depression isn't acknowledged as a contributing factor. This is true despite the fact that the painkilling mechanism of these medications is not completely understood.2

However, a new investigation into the use of antidepressants for chronic pain found that there was no reliable evidence to support either long-term efficacy or safety. The study, which is the largest of its kind to have been done, was published in the Cochrane Database of Systematic Reviews.3

“This is a global public health concern,” said Tamar Pincus, lead author on the study and a professor at the University of Southampton. “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.”

Investigators from several universities across the United Kingdom conducted a network meta-analysis to determine if antidepressants were effective for managing chronic pain and if there were any unwanted effects associated with their use. In total, 176 trials consisting of 28,644 people with chronic pain were included.

Studies in the meta-analysis investigated 89 different types or combinations of antidepressants for their effect on chronic pain conditions, such as fibromyalgia, nerve pain and musculoskeletal pain. The three most common medications that were examined were amitriptyline, duloxetine and milnacipran.

Primary outcomes were substantial (50%) pain relief, pain intensity, mood, and adverse events. Secondary outcomes included moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change (PGIC), serious adverse events, and withdrawal.

Investigators found that duloxetine was the highest-rated medication and showed a moderate effect on reducing pain and improving physical function. A standard dose was found to be as successful at reducing pain as a higher dose.

A standard dose of milnacipran also showed a small effect, but the researchers were not as confident in this result due to fewer studies that involved less people.

“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 Pincus. “Though we did find that duloxetine provided short-term pain relief for patients we studied, we remain concerned about its possible long-term harm due to the gaps in current evidence.”

The researchers noted that because most of the studies excluded people with mental health conditions and participants were already in the 'normal' ranges for anxiety and depression, an analysis of mood was limited.

Additionally, due to a lack of data, there was low certainty of evidence for all safety outcomes across each of the antidepressants examined.

“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,” said Gavin Stewart, review co-author and a lecturer at the University of Newcastle. “Evidence synthesis is often complex and nuanced but the evidence underpinning the use of these treatments is not equivalent, so current treatment modalities are hard to justify.”

1. Ferreira G E, Abdel-Shaheed C, Underwood M, Finnerup N B, Day R O, McLachlan A et al. Efficacy, safety, and tolerability of antidepressants for pain in adults: overview of systematic reviews. BMJ. 2023;380:e072415. doi:10.1136/bmj-2022-072415.
2. Antidepressants: Another weapon against chronic pain. Mayo Clinic. September 7, 2019. Accessed May 11, 2023.
3. Birkinshaw H, Friedrich CM, Cole P, Eccleston C, Serfaty M, Stewart G, White S, Moore RA, Phillippo D, Pincus T. Antidepressants for pain management in adults with chronic pain: a network meta‐analysis. Cochrane Database of Systematic Reviews 2023, Issue 5. No. CD014682. DOI: 10.1002/14651858.CD014682.pub2.
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