Antidepressant Shows Promising Efficacy in Certain People for Chronic Pain Management


Common chronic pain conditions included in the analysis were fibromyalgia, neuropathic pain, and musculoskeletal pain.

Duloxetine (Cumbalta, Eli Lilly and Company) is the only antidepressant that researchers are confident will treat chronic pain, according to the results of a review and network meta‐analysis (NMA) of 176 studies on antidepressants for chronic pain published in Cochrane Library. For every 1000 people who took standard-dose duloxetine, 43.5% experienced at least 50% pain relief compared to 28.7% of those on placebo.

Credit: pankajstock123 -

Credit: pankajstock123 -

More than 33% of individuals experience chronic pain worldwide. Chronic pain is defined as any type of pain that lasts more than 3 months, and can impact well-being, mood, and the ability to work and perform daily tasks.

Many antidepressants function differently, but those that function similarly are grouped into classes. The main antidepressant classes are selective serotonin reuptake inhibitors (SSRIs), norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs). Investigators suggest that antidepressants could effectively ameliorate symptoms of chronic pain because mood and pain may be regulated by similar chemicals.

In an NMA and review, investigators aimed to evaluate the efficacy and safety of antidepressants for adults with chronic pain (excluding headache) and examined whether they cause unwanted adverse events (AEs).

The analysis included 176 studies, the majority of which were placebo-controlled and parallel-armed, with 28,664 participants total. The most common chronic pain conditions included in the studies were fibromyalgia, neuropathic pain, and musculoskeletal pain, and most trials evaluated short-term outcomes.

The review included 74 studies that evaluated SNRIs for chronic pain, 72 that evaluated TCAs, and 34 that evaluated SSRIs. The most common antidepressants investigated include the TCA amitriptyline (Elavil, Vanatrip), the SNRI duloxetine, and the SNRI milnacipran (Savella, Dalcipran, Toledomin).

After the review, duloxetine was the only antidepressant that investigators expressed certainty for in treating chronic pain. Milnacipran was found to reduce chronic pain; however, there were fewer people and studies to confirm these effects. There is moderate-certain evidence that both provide moderate pain relief, physical function, sleep, and quality of life.

The data also showed that patients who received a higher-than-standard dose of duloxetine did not gain additional benefits than the standard dose of 60 mg. Investigators are not certain that any of the antidepressants achieved safety outcomes.

The study includes some limitations. Investigators have little confidence in the efficacy results of any antidepressant besides duloxetine. In addition, there is little certainty on antidepressants for long-term pain relief, no reliable evidence on its safety in the short- or long-term, and most studies excluded patients with mental health conditions outside of the “normal” ranges for anxiety and depression, limiting analysis for effect on mood.

“Adopting a person‐centered approach is critical. Pain is a very individual experience and certain medications may work for people even while the research evidence is inconclusive or unavailable,” the study authors wrote in the article. “Future studies should last longer and focus on unwanted effects of antidepressants.”


Birkinshaw H, Friedrich C, Cole P, et al. Antidepressants for pain management in adults with chronic pain: a network meta‐analysis. Cochrane Library. May 10, 2023. Accessed May 11, 2023.

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