New Review Finds Antidepressants Are Ineffective for Treating Chronic Pain

Depression and pain conditions share several neural pathways. Estimates suggest that 35–45% of people with chronic pain experience depression.

Earlier this year, a meta-analysis of 26 studies found that antidepressants were effective in relieving pain in around 25% of cases. However, for the remaining 75% of cases, antidepressants were either inefficacious or data was inconclusive.

Understanding more about the potential of antidepressants for treating chronic pain could improve treatment options for the condition. 

A new review, published in the Cochrane Database of Systematic Reviews also assessed the efficacy of antidepressants in treating adults with chronic pain.

For the review, the researchers analyzed data from 176 studies including 28,664 participants who had fibromyalgia, neuropathic pain, or musculoskeletal pain.

In the end, the researchers found no evidence that antidepressants can induce long-term pain relief for chronic pain conditions.

They did find, however, that duloxetine may have a moderate effect on short-term pain relief. Of every 1,000 people taking the drug, 435 experienced 50% pain relief compared to 287 experiencing 50% pain relief on a placebo. The researchers noted that gaps in current evidence mean that the effects of long-term duloxetine use remain unknown.

They also found that milnacipran may also reduce pain. However, they noted that further research is needed due to the few studies that reviewed this drug.

Dr. Akshay Goyal, double board-certified pain management physician at Baptist Health Miami Neuroscience Institute, not involved in the study said: “Both duloxetine and milnacipran offer some advantages to pain. The reason is that these medications work on norepinephrine, implicated in pain perception, as well as serotonin, implicated in depression.”

He also noted that both duloxetine and milnacipran are serotonin and norepinephrine uptake inhibitors (SNRIs), meaning the medications prevent the breakdown of these neurotransmitters. He indicated that higher levels of both norepinephrine and serotonin are responsible for improvements in pain perception. 


Hollie Birkinshaw, Claire M Friedrich, Peter Cole, Christopher Eccleston, Marc Serfaty, Gavin Stewart, Simon White, R Andrew Moore, David Phillippo, Tamar Pincus. Antidepressants for pain management in adults with chronic pain: a network meta‐analysis. (Cochrane 2023). 

Annie Lennon (May 16, 2023). Antidepressants are ineffective for treating chronic pain, review finds. MedicalNewsToday. Retrieved May 16, 2023 from: 

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